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HEMATOLOGY (160 journals)                     

Showing 1 - 151 of 151 Journals sorted alphabetically
Acta Angiologica     Open Access   (Followers: 3)
Acta Haematologica     Full-text available via subscription   (Followers: 23)
Acta Haematologica Polonica     Open Access  
Adipocyte     Open Access  
Advances in Hematology     Open Access   (Followers: 13)
Africa Sanguine     Full-text available via subscription  
American Journal of Hematology     Hybrid Journal   (Followers: 52)
Anemia     Open Access   (Followers: 6)
Annals of Hematology     Hybrid Journal   (Followers: 16)
Archives of Hematology Case Reports and Reviews     Open Access  
Arteriosclerosis, Thrombosis and Vascular Biology     Full-text available via subscription   (Followers: 28)
Artery Research     Hybrid Journal   (Followers: 4)
Artificial Cells, Nanomedicine and Biotechnology     Hybrid Journal   (Followers: 4)
ASAIO Journal     Hybrid Journal   (Followers: 2)
Best Practice & Research Clinical Haematology     Hybrid Journal   (Followers: 5)
Blood     Hybrid Journal   (Followers: 307)
Blood Advances     Open Access   (Followers: 7)
Blood and Lymphatic Cancer : Targets and Therapy     Open Access   (Followers: 7)
Blood Cancer Journal     Open Access   (Followers: 19)
Blood Cells, Molecules, and Diseases     Hybrid Journal   (Followers: 8)
Blood Coagulation & Fibrinolysis     Hybrid Journal   (Followers: 60)
Blood Pressure     Open Access  
Blood Pressure Monitoring     Hybrid Journal   (Followers: 1)
Blood Purification     Full-text available via subscription   (Followers: 6)
Blood Reviews     Hybrid Journal   (Followers: 26)
BMC Hematology     Open Access   (Followers: 7)
BMJ Open Diabetes Research & Care     Open Access   (Followers: 29)
Bone Marrow Transplantation     Hybrid Journal   (Followers: 17)
British Journal of Diabetes & Vascular Disease     Open Access   (Followers: 21)
British Journal of Haematology     Hybrid Journal   (Followers: 61)
British Journal of Primary Care Nursing - Cardiovascular Disease, Diabetes and Kidney Care     Full-text available via subscription   (Followers: 10)
Canadian Journal of Diabetes     Hybrid Journal   (Followers: 28)
Case Reports in Hematology     Open Access   (Followers: 10)
Clinical and Applied Thrombosis/Hemostasis     Open Access   (Followers: 32)
Clinical Diabetes     Full-text available via subscription   (Followers: 40)
Clinical Diabetes and Endocrinology     Open Access   (Followers: 20)
Clinical Lymphoma & Myeloma     Full-text available via subscription   (Followers: 2)
Clinical Lymphoma Myeloma and Leukemia     Hybrid Journal   (Followers: 5)
Clinical Medicine Insights : Blood Disorders     Open Access   (Followers: 1)
Conquest : The Official Journal of Diabetes Australia     Full-text available via subscription   (Followers: 3)
Current Angiogenesis     Hybrid Journal   (Followers: 1)
Current Diabetes Reports     Hybrid Journal   (Followers: 24)
Current Diabetes Reviews     Hybrid Journal   (Followers: 27)
Current Hematologic Malignancy Reports     Hybrid Journal   (Followers: 2)
Current Opinion in Hematology     Hybrid Journal   (Followers: 20)
Cytotherapy     Full-text available via subscription   (Followers: 2)
Der Diabetologe     Hybrid Journal   (Followers: 2)
Diabetes     Full-text available via subscription   (Followers: 418)
Diabetes aktuell     Hybrid Journal   (Followers: 3)
Diabetes and Vascular Disease Research     Hybrid Journal   (Followers: 20)
Diabetes Care     Full-text available via subscription   (Followers: 478)
Diabetes Case Reports     Open Access  
Diabetes Educator     Hybrid Journal   (Followers: 27)
Diabetes Management     Full-text available via subscription   (Followers: 15)
Diabetes Research and Clinical Practice     Hybrid Journal   (Followers: 70)
Diabetes Spectrum     Full-text available via subscription   (Followers: 17)
Diabetes Technology & Therapeutics     Hybrid Journal   (Followers: 50)
Diabetes Therapy     Open Access   (Followers: 23)
Diabetic Foot & Ankle     Open Access   (Followers: 10)
Diabetic Medicine     Hybrid Journal   (Followers: 149)
Diabetologia     Hybrid Journal   (Followers: 215)
Diabetologia Kliniczna     Hybrid Journal  
Diabetologie und Stoffwechsel     Hybrid Journal   (Followers: 2)
Egyptian Journal of Haematology     Open Access  
eJHaem     Open Access  
European Journal of Haematology     Hybrid Journal   (Followers: 16)
Experimental Hematology     Hybrid Journal   (Followers: 6)
Experimental Hematology & Oncology     Open Access   (Followers: 6)
Expert Review of Hematology     Hybrid Journal   (Followers: 5)
Fluids and Barriers of the CNS     Open Access   (Followers: 1)
Global Journal of Transfusion Medicine     Open Access   (Followers: 1)
Haematologica - the Hematology journal     Open Access   (Followers: 34)
Haemophilia     Hybrid Journal   (Followers: 68)
Hematologia     Full-text available via subscription   (Followers: 3)
Hematología     Open Access  
Hematology     Open Access   (Followers: 15)
Hematology Reports     Open Access   (Followers: 4)
Hematology, Transfusion and Cell Therapy     Open Access   (Followers: 2)
Hematology/Oncology and Stem Cell Therapy     Open Access   (Followers: 6)
Hemodialysis International     Hybrid Journal   (Followers: 3)
Hepatitis Monthly     Open Access   (Followers: 3)
Immunohematology : Journal of Blood Group Serology and Molecular Genetics     Hybrid Journal   (Followers: 1)
Indian Journal of Hematology and Blood Transfusion     Hybrid Journal   (Followers: 2)
Info Diabetologie     Full-text available via subscription   (Followers: 1)
InFo Hämatologie + Onkologie : Interdisziplinäre Fortbildung von Ärzten für Ärzte     Full-text available via subscription  
Integrated Blood Pressure Control     Open Access  
International Blood Research & Reviews     Open Access  
International Journal of Clinical Transfusion Medicine     Open Access   (Followers: 3)
International Journal of Diabetes in Developing Countries     Hybrid Journal   (Followers: 6)
International Journal of Diabetes Research     Open Access   (Followers: 9)
International Journal of Hematologic Oncology     Open Access   (Followers: 2)
International Journal of Hematology     Hybrid Journal   (Followers: 4)
International Journal of Hematology Research     Open Access   (Followers: 2)
International Journal of Hematology-Oncology and Stem Cell Research     Open Access   (Followers: 2)
International Journal of Laboratory Hematology     Hybrid Journal   (Followers: 25)
Iraqi Journal of Hematology     Open Access  
JMIR Diabetes     Open Access  
Journal of Blood Disorders & Transfusion     Open Access   (Followers: 3)
Journal of Applied Hematology     Open Access   (Followers: 2)
Journal of Blood Medicine     Open Access   (Followers: 1)
Journal of Cerebral Blood Flow & Metabolism     Hybrid Journal   (Followers: 3)
Journal of Diabetes     Open Access   (Followers: 20)
Journal of Diabetes and its Complications     Hybrid Journal   (Followers: 25)
Journal of Diabetes and Metabolic Disorders     Open Access   (Followers: 7)
Journal of Diabetes Investigation     Open Access   (Followers: 12)
Journal of Diabetes Mellitus     Open Access   (Followers: 5)
Journal of Diabetes Research     Open Access   (Followers: 13)
Journal of Diabetes Research     Open Access   (Followers: 10)
Journal of Hematological Malignancies     Open Access  
Journal of Hematology     Open Access   (Followers: 2)
Journal of Hematology and Transfusion Medicine     Open Access   (Followers: 1)
Journal of Hematopathology     Hybrid Journal   (Followers: 3)
Journal of Hypo & Hyperglycemia     Partially Free   (Followers: 1)
Journal of Pediatric Hematology/Oncology     Hybrid Journal   (Followers: 8)
Journal of Social Health and Diabetes     Open Access   (Followers: 1)
Journal of Thrombosis and Haemostasis     Hybrid Journal   (Followers: 81)
Journal of Thrombosis and Thrombolysis     Hybrid Journal   (Followers: 35)
Journal of Transfusion Medicine     Full-text available via subscription  
Kidney and Blood Pressure Research     Open Access   (Followers: 4)
Leukemia     Hybrid Journal   (Followers: 23)
Leukemia and Lymphoma     Hybrid Journal   (Followers: 12)
Leukemia Research     Hybrid Journal   (Followers: 9)
Leukemia Research Reports     Open Access   (Followers: 1)
Leukemia Supplements     Full-text available via subscription  
Mediterranean Journal of Hematology and Infectious Diseases     Open Access  
Nederlands Tijdschrift voor Diabetologie     Hybrid Journal  
Nutrition & Diabetes     Open Access   (Followers: 20)
Oncohematology     Open Access   (Followers: 1)
Open Diabetes Journal     Open Access  
Open Hematology Journal     Open Access   (Followers: 1)
Open Hypertension Journal     Open Access  
Open Journal of Blood Diseases     Open Access  
Pediatric Blood & Cancer     Hybrid Journal   (Followers: 8)
Pediatric Hematology Oncology Journal     Open Access   (Followers: 3)
Peritoneal Dialysis International     Hybrid Journal  
Platelets     Hybrid Journal   (Followers: 3)
Practical Diabetes     Hybrid Journal   (Followers: 7)
Primary Care Diabetes     Hybrid Journal   (Followers: 26)
Research & Reviews : Journal of Oncology and Hematology     Full-text available via subscription   (Followers: 1)
Research and Practice in Thrombosis and Haemostasis     Open Access   (Followers: 1)
Revista Cubana de Hematología, Inmunología y Hemoterapia     Open Access  
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Seminars in Thrombosis and Hemostasis     Hybrid Journal   (Followers: 45)
Thalassemia Reports     Open Access   (Followers: 1)
The Lancet Haematology     Full-text available via subscription   (Followers: 38)
Therapeutic Advances in Hematology     Hybrid Journal  
Thrombosis & Haemostasis     Hybrid Journal   (Followers: 144)
Thrombosis Research     Hybrid Journal   (Followers: 47)
Transfusionsmedizin - Immunhämatologie, Hämotherapie, Immungenetik, Zelltherapie     Hybrid Journal  
Transplantation and Cellular Therapy     Hybrid Journal   (Followers: 13)
Veins and Lymphatics     Open Access   (Followers: 1)

           

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Journal Cover
Therapeutic Advances in Hematology
Number of Followers: 0  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 2040-6207 - ISSN (Online) 2040-6215
Published by Sage Publications Homepage  [1175 journals]
  • Association between haploidentical hematopoietic stem cell transplantation
           combined with an umbilical cord blood unit and graft-versus-host disease
           in pediatric patients with acquired severe aplastic anemia

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      Authors: Di Yao, Yuanyuan Tian, Jie Li, Bohan Li, Jun Lu, Jing Ling, Defei Zheng, Yanhua Yao, Peifang Xiao, Lijun Meng, Shaoyan Hu
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) based on granulocyte colony-stimulating factor plus anti-thymocyte regimens (‘Beijing Protocol’) provides a salvage treatment for patients of acquired severe aplastic anemia (SAA) in China. However, graft-versus-host disease (GVHD) is a major impediment of haplo-HSCT due to human leukocyte antigen disparity. Recently, haplo-HSCT combined with umbilical cord blood (UCB) (haplo-cord HSCT) is performed in clinical trials to potentially reduce the risk of severe GVHD. Nevertheless, studies comparing GVHD in pediatric patients receiving haplo and haplo-cord HSCT for SAA are limited.Objective:The objective of this study was to investigate the impact of UCB co-infusion on GVHD in pediatric patients receiving haplo-HSCT for SAA.Design:We conducted a retrospective study of 91 consecutive SAA children undergoing haploidentical transplantation based on the ‘Beijing Protocol’ with or without co-infusion of UCB in our center.Methods:All patients received uniform non-myeloablative conditioning and GVHD prophylaxis. We compared baseline characteristics and transplant outcomes between the haplo (n = 35) and haplo-cord (n = 56) recipients.Results:All 91 patients achieved hematopoietic recovery from haploidentical donors, with a higher incidence of peri-engraftment syndrome observed with the haplo-cord group as compared with the haplo group (75.0% versus 48.6%, p = 0.029). Notably, the haplo-cord group showed a lower incidence of II–IV acute GVHD (aGVHD) than the haplo group (16.1% versus 42.9%, p = 0.002). Observed incidences of chronic GVHD (cGVHD) and moderate to severe cGVHD in the haplo-cord group were also lower than that in the haplo group (25.6% versus 51.3%, p = 0.019; 16.2% versus 41.3%, p = 0.016, respectively). Haplo-cord HSCT was identified as the only factor associated with a lower incidence of II–IV aGVHD and cGVHD in multivariate analysis. However, no differences were observed between the two groups for infections and survival outcomes.Conclusion:Our data indicated that co-infusion of UCB in ‘Beijing Protocol’-based haplo-HSCT may be effective for reducing the risk of severe GVHD in SAA children.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-10-28T08:28:07Z
      DOI: 10.1177/20406207221134409
      Issue No: Vol. 13 (2022)
       
  • Serum proteomics screening intercellular adhesion molecule-2 improves
           intermediate-risk stratification in acute myeloid leukemia

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      Authors: Nan Zhang, Xiaoyan Liu, Jinxian Wu, Xinqi Li, Qian Wang, Guopeng Chen, Linlu Ma, Sanyun Wu, Fuling Zhou
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:The clinical risk classification of acute myelocytic leukemia (AML) is largely based on cytogenetic and molecular genetic detection. However, the optimal treatment for intermediate-risk AML patients remains uncertain. Further refinement and improvement of prognostic stratification are therefore necessary.Objectives:The aim of this study was to identify serum protein biomarkers to refine risk stratification in AML patients.Design:This study is a retrospective study.Methods:Label-free proteomics was used to identify the differential abundance of serum proteins in AML patients. Transcriptomic data were combined to identify key altered markers that could indicate the risk rank of AML patients. The survival status was assessed by Kaplan–Meier and multivariate Cox regression analyses.Results:We delineated serum protein expression in a population of AML patients. Many biological processes were influenced by the identified differentially expressed proteins. Association analysis of transcriptome data showed that intercellular adhesion molecule-2 (ICAM2) had a higher survival prediction value in the intermediate-risk AML group. ICAM2 was detrimental for intermediate-risk AML, regardless of whether patients received bone marrow transplantation. ICAM2 well distinguishes the intermediate group of patients, whose probability of survival is comparable to that of patients with the ELN-2017 according to the reference classification. In addition, newly established stratified clinical features were associated with leukemia stem cell scores.Conclusion:The inclusion of ICAM2 expression into the AML risk classification according to ELN-2017 was a good way to transfer patients from three to two groups. Thus, providing more information for clinical decision-making to improve intermediate-risk stratification in AML patients.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-10-28T08:20:30Z
      DOI: 10.1177/20406207221132346
      Issue No: Vol. 13 (2022)
       
  • Coexisting conditions and concomitant medications do not affect venetoclax
           management and survival in chronic lymphocytic leukemia

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      Authors: Anna Maria Frustaci, Giovanni Del Poeta, Andrea Visentin, Paolo Sportoletti, Alberto Fresa, Candida Vitale, Roberta Murru, Annalisa Chiarenza, Alessandro Sanna, Francesca Romana Mauro, Gianluigi Reda, Massimo Gentile, Marzia Varettoni, Claudia Baratè, Chiara Borella, Antonino Greco, Marina Deodato, Giulia Zamprogna, Roberta Laureana, Alessandra Cipiciani, Andrea Galitzia, Angelo Curto Pelle, Francesca Morelli, Lucio Malvisi, Marta Coscia, Luca Laurenti, Livio Trentin, Marco Montillo, Roberto Cairoli, Alessandra Tedeschi
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia (CLL) is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events.Objectives:This study was aimed to evaluate whether age, fitness status, patients’/disease characteristics, or concomitant medications may predict outcomes in CLL patients receiving venetoclax.Design:Retrospective observational study.Methods:Impact of age, presence of Cumulative Illness Rating Scale (CIRS)>6 or severe organ impairment (CIRS3+), Eastern Cooperative Oncology Group–Performance Status (ECOG-PS), renal function, and concomitant medications were retrospectively analyzed on treatment management (definitive discontinuation due to toxicity, discontinuation due to toxicity, Tox-DTD; permanent dose reduction, PDR) and survival [progression free survival (PFS), event free survival (EFS), overall survival (OS)] in unselected patients receiving venetoclax monotherapy in common practice.Results:A total of 221 relapsed/refractory patients were included. Tox-DTD and PDR were reported in 5.9% and 21.7%, respectively, and were not influenced by any fitness parameter, age, number or type of concomitant medication, baseline neutropenia, or impaired renal function. None of these factors were associated with tumor lysis syndrome (TLS) development. Age and coexisting conditions had no influence on PFS and EFS. At univariate analysis, OS was significantly shorter only in patients with ECOG-PS>1 (p 6 (p = 0.014) or CIRS3+ (p = 0.031). ECOG-PS>1 retained an independent role only for EFS and OS. While Tox-DTD affected all survival outcomes, no differences in PFS were reported among patients permanently reducing dose or interrupting venetoclax for> 7 days.Conclusion:Clinical outcome with venetoclax is not influenced by comorbidities, patients’ clinical characteristics, or concomitant medications. Differently from other targeted therapies, this demonstrates that, except ECOG-PS, none of the parameters generally considered for treatment choice, including baseline neutropenia or impaired renal function, should rule the decision process with this agent. Anyway, if clinically needed, a correct drug management does not compromise treatment efficacy and may avoid toxicity-driven discontinuations.Plain Language SummaryChapter 1: Why was this study done'Chapter 2: Which are the main findings of the study'Chapter 3: How these findings may impact on clinical practice'Coexisting conditions and concomitant medications do not affect venetoclax management and survival in chronic lymphocytic leukemia• The question of which parameters may be informative on venetoclax outcome in chronic lymphocytic leukemia is still unclear. Furthermore, the choice to treat with venetoclax can be challenging in patients with baseline characteristics or comorbidities that may potentially favor some specific adverse events (e.g. compromised renal function or baseline neutropenia).• In our large series of patients treated outside of clinical trials, we demonstrated that neither age, fitness, comorbidities nor concomitant medications impact on venetoclax management and survival. Importantly, patients presenting with baseline neutropenia or impaired renal function did not have a higher rate of dose reductions or toxicity-driven discontinuations, thus further underlining that venetoclax may be safely administered even in those categories with no preclusions.• Differently from other targeted agents, our data demonstrate that none of the baseline factors commonly considered in treatment decision process retains a role with venetoclax. Finally, permanent dose reductions and temporary interruptions did not adversely impact PFS suggesting that, if clinically needed, a correct drug management should be adopted with no risk of compromising venetoclax efficacy.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-10-11T06:21:06Z
      DOI: 10.1177/20406207221127550
      Issue No: Vol. 13 (2022)
       
  • Circulating HMGB1 is increased in myelodysplastic syndrome but not in
           other bone marrow failure syndromes: proof-of-concept cross-sectional
           study

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      Authors: Elia Apodaca-Chávez, Roberta Demichelis-Gómez, Adriana Rosas-López, Nancy R. Mejía-Domínguez, Isabela Galvan-López, Meghan Addorosio, Kevin J. Tracey, Sergio Iván Valdés-Ferrer
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Myelodysplastic syndrome (MDS) is associated with persistent immune activation. High mobility group box-1 (HMGB1) is a ubiquitous, functionally diverse, non-histone intranuclear protein. During acute and chronic inflammatory states, HMGB1 is actively released by inflammatory cells, further amplifying the inflammatory response. A role in MDS and other hypoplastic bone marrow (BM) disorders is incompletely understood.Objectives:The objective of the study is to evaluate whether circulating HMGB1 is elevated in patients with MDS and other BM failure syndromes [namely, aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH)].Design:This is a observational, cross-sectional, single-center, exploratory study.Methods:We evaluated circulating concentrations of HMGB1, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in patients with MDS and age-matched hematologically healthy controls as well as patients with AA and PNH.Results:We included 66 patients with MDS and 65 age-matched controls as well as 44 patients with other BM failures (AA = 27, PNH = 17). Circulating levels of HMGB1 were higher in patients with MDS [median, 4.9 ng/ml; interquartile range (IQR): 2.3–8.1] than in AA (median, 2.6 ng/ml; IQR: 1.7–3.7), PNH (median, 1.7 ng/ml; IQR: 0.9–2.5), and age-matched healthy individuals (median, 1.9 ng/ml; IQR: 0.9–2.5) (p = 0.0001). We observed higher concentrations of HMGB1 in the very low/low-risk MDS patients than in the intermediate/high/very high-risk ones (p = 0.046). Finally, in comparison with patients with AA, those with hypocellular MDS (h-MDS) had significantly higher levels of circulating HMGB1 (n = 14; median concentration, 5.6 ng/ml, IQR: 2.8–7.3; p = 0.006). We determined a circulating HMGB1 value of 4.095 ng/ml as a diagnostic cutoff differentiator between h-MDS and AA.Conclusion:These observations indicate that circulating HMGB1 is increased in patients with MDS. HMGB1 (but not IL-1β or TNF-α) differentiated between MDS and other BM failures, suggesting that HMGB1 may be mechanistically involved in MDS and a druggable target to decrease inflammation in MDS.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-10-11T06:16:42Z
      DOI: 10.1177/20406207221125990
      Issue No: Vol. 13 (2022)
       
  • Relevance of infections on the outcomes of patients with myelodysplastic
           syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia
           treated with hypomethylating agents: a cohort study from the GESMD

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      Authors: Laura Vilorio-Marqués, Christelle Castañón Fernández, Elvira Mora, Lorena Gutiérrez, Beatriz Rey Bua, Maria José Jiménez Lorenzo, Marina Díaz Beya, Miriam Vara Pampliega, Antonieta Molero, Joaquín Sánchez-García, Marisa Calabuig, Maria Teresa Cedena, Tzu Chen-Liang, Johana Alejandra Díaz Santa, Irene Padilla, Francisca Hernández, Rosana Díez, Pedro Asensi, Blanca Xicoy, Guillermo Sanz, David Valcárcel, María Diez-Campelo, Teresa Bernal
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:The consequences of infectious toxicity of hypomethylating agents (HMAs) on overall survival (OS) of patients diagnosed with high-risk myeloid neoplasms have not been thoroughly investigated.Objectives:We aimed to evaluate whether infectious events (IEs) negatively influenced the results of HMA treatment in a real-world setting.Design:Observational study.Methods:We obtained data from 412 non-selected consecutive patients from 23 Spanish hospitals who were diagnosed with high-risk myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia and were treated with HMA. HMAs received after chemotherapy or stem cell transplant were excluded. All IEs were recorded. Outcomes included OS, modifications to the pre-planned treatment, incidence and characteristics of IEs, hospitalization, red blood cell transfusions, and factors associated with infection.Results:The rate of infection was 1.2 per patient/year. Next-cycle delay (p = 0.001) and hospitalizations (p = 0.001) were significantly influenced by IEs. Transfusion requirements during each cycle were significantly higher after infection compared with cycles without infection (coefficient = 1.55 [95% confidence interval (CI) = 1.26–1.84], p 
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-09-29T12:06:51Z
      DOI: 10.1177/20406207221127547
      Issue No: Vol. 13 (2022)
       
  • Avatrombopag for the treatment of thrombocytopenia post hematopoietic
           stem-cell transplantation

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      Authors: Meng Zhou, Jiaqian Qi, Chengyuan Gu, Hong Wang, Ziyan Zhang, Depei Wu, Yue Han
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Thrombocytopenia post hematopoietic stem-cell transplantation (HCT) usually contributes to poor outcomes with no standardized treatment. Eltrombopag and romiplostim can be feasible for post-HCT thrombocytopenia, but the use of avatrombopag has not yet been evaluated.Objectives:We aimed to evaluate the efficacy and safety of avatrombopag treatment in patients diagnosed with post-HCT thrombocytopenia.Design:In this retrospective study, we evaluated the efficacy and safety of avatrombopag treatment in a cohort of 61 patients diagnosed with thrombocytopenia post HCT in our clinical center.Methods:Avatrombopag was initiated at 20 mg daily, with a dosage adjustment to achieve platelet recovery to >20 × 109/l independent from transfusion for 7 consecutive days (overall response, OR) or to >50 × 109/l free from transfusion for 7 consecutive days (complete response, CR). Factors influencing OR and CR were studied in univariate and multivariate analyses, respectively. Within the follow-up, adverse events like myelofibrosis, thrombosis, and organ toxicities were monitored carefully.Results:The overall response rate (ORR) to avatrombopag was 68.9% and the cumulative incidence (CI) of OR was 69.1%. The complete response rate (CRR) and the CI of CR were both 39.3%. The median days from avatrombopag initiation to OR and CR were 21 and 25 days, respectively. An adequate number of megakaryocytes before the initiation of avatrombopag was an independent protective factor of avatrombopag treatment for OR (hazard ratio, HR = 4.628, 95% confidence interval 1.92–11.15, p = 0.0006) and CR (HR = 4.892, 95% confidence interval 1.58–15.18, p = 0.006). Avatrombopag was well tolerated in all patients with no severe adverse events.Conclusion:Our findings suggested that avatrombopag can be optional for thrombocytopenia post HCT.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-09-28T10:29:49Z
      DOI: 10.1177/20406207221127532
      Issue No: Vol. 13 (2022)
       
  • Efficacy and safety of ruxolitinib in patients with myelofibrosis and low
           platelet count (50 × 109/L to

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      Authors: Paola Guglielmelli, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Minghui Duan, Haitao Meng, Ling Pan, Guangsheng He, Srdan Verstovsek, Françoise Boyer, Fiorenza Barraco, Dietger Niederwieser, Ester Pungolino, Anna Marina Liberati, Claire Harrison, Pantelia Roussou, Monika Wroclawska, Divyadeep Karumanchi, Karen Sinclair, Peter A.W. te Boekhorst, Heinz Gisslinger
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Thrombocytopenia is a common feature of myelofibrosis (MF), a myeloproliferative neoplasm driven by dysregulated JAK/STAT signaling; however, pivotal trials assessing the efficacy of ruxolitinib (a JAK1/2 inhibitor) excluded MF patients with low platelet counts (
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-09-10T09:45:42Z
      DOI: 10.1177/20406207221118429
      Issue No: Vol. 13 (2022)
       
  • Recent advances in immunotherapy for B-cell non-Hodgkin lymphoma and
           multiple myeloma

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      Authors: Julio C. Chavez, Mohamed A. Kharfan-Dabaja
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.

      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-09-05T07:10:36Z
      DOI: 10.1177/20406207221116578
      Issue No: Vol. 13 (2022)
       
  • Spatial heterogeneity and differential treatment response of acute myeloid
           leukemia and relapsed/refractory extramedullary disease after allogeneic
           hematopoietic cell transplantation

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      Authors: Desiree Kunadt, Sylvia Herold, David Poitz, Lisa Wagenführ, Theresa Kretschmann, Katja Sockel, Leo Ruhnke, Stefan Brückner, Ulrich Sommer, Frieder Meier, Christoph Röllig, Malte von Bonin, Christian Thiede, Johannes Schetelig, Martin Bornhäuser, Friedrich Stölzel
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Although extramedullary manifestations (EMs) are frequent in patients with acute myeloid leukemia (AML), they are often not detected during clinical workup and neither imaging- nor molecularly based diagnostic strategies are established to reveal their existence. Still, the detection of EM is essential for therapeutic decision-making, as EM present with aggressive and resistant disease and since mutational profiling might render patients within a different risk category, requiring personalized therapeutic strategies. Here, we report the case of an AML patient presenting with AML bone marrow (BM) infiltration and molecularly distinct EM at time of diagnosis followed by multiple EM relapses while undergoing several intensive chemotherapies including allogeneic hematopoietic cell transplantations (alloHCTs). 18Fluorodesoxy-glucose positron emission tomography (18FDG-PET)-imaging revealed EM sites in the mediastinum, duodenum, skin, and in retroperitoneal tissue, whereas recurrent BM biopsies showed continuous cytomorphologic and cytogenetic remission after alloHCT. To investigate the molecular background of the aggressive character of extramedullary disease and its differential treatment response, we performed amplicon-based next generation sequencing. An exon 4 (c.497_498insGA) frameshift RUNX1 mutation was exclusively found in all of the patient’s EM sites, but not in the BM or in peripheral blood samples at time of EM reoccurrence. In addition, we detected an exon 13 (c.3306G>T) ASXL1 point mutation only in the retroperitoneal tumor tissue at the time of the fourth relapse. In contrast to the patient’s intermediate-risk BM AML at diagnosis according to ELN2017, EM sites showed molecular adverse-risk features implicating intensified strategies like cellular therapies. Notably, disease relapse could only be detected by imaging throughout the course of disease. This case demonstrates both the necessity of continuous molecular profiling of EM to reveal differential molecular composition of EM and BM-derived AML, supposedly leading to divergent susceptibility to established therapies, as well as recurrent 18FDG-PET-imaging for detecting residual disease and assessment of treatment response in case of EM AML.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-08-23T11:14:15Z
      DOI: 10.1177/20406207221115005
      Issue No: Vol. 13 (2022)
       
  • Selecting the optimal BTK inhibitor therapy in CLL: rationale and
           practical considerations

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      Authors: Alexandra R. Lovell, Nadya Jammal, Prithviraj Bose
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Bruton’s tyrosine kinase (BTK) inhibitors have dramatically changed the treatment of newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL). Ibrutinib, acalabrutinib, and zanubrutinib are Food and Drug Administration (FDA)-approved BTK inhibitors that have all demonstrated progression-free survival (PFS) benefit compared with chemoimmunotherapy. The efficacy of these agents compared to one another is under study; however, current data suggest they provide similar efficacy. Selectivity for BTK confers different adverse effect profiles, and longer follow-up and real-world use have characterized side effects over time. The choice of BTK inhibitor is largely patient-specific, and this review aims to highlight the differences among the agents and guide the choice of BTK inhibitor in clinical practice.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-08-09T12:59:15Z
      DOI: 10.1177/20406207221116577
      Issue No: Vol. 13 (2022)
       
  • Safety and efficacy of pegcetacoplan in paroxysmal nocturnal
           hemoglobinuria

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      Authors: Raymond S.M. Wong
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by complement-mediated hemolysis, thrombosis, and various degrees of bone marrow dysfunction. Until recently, C5 inhibition with eculizumab or ravulizumab represented the only therapies approved for patients with PNH by the United States Food and Drug Administration (US FDA). Although C5-inhibitors reduce PNH-related signs and symptoms, many patients continue to exhibit persistent anemia and require frequent blood transfusions. In May 2021, pegcetacoplan became the third US FDA-approved treatment for adults with PNH, and the first to target C3, a complement component upstream of C5. The novel strategy of inhibiting proximal complement activity with pegcetacoplan controls C5-mediated intravascular hemolysis and prevents C3-mediated extravascular hemolysis. Here, we review the results from multiple pegcetacoplan clinical studies on the efficacy and safety of pegcetacoplan treatment in adults with PNH. This review summarizes findings from three studies in complement-inhibitor-naïve patients with PNH (PADDOCK [phase Ib], PALOMINO [phase IIa], PRINCE [phase III; pegcetacoplan versus standard treatment excluding complement-inhibitors]), and one phase III study (PEGASUS) that compared eculizumab to pegcetacoplan in patients who remained anemic (hemoglobin levels 
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-28T10:58:36Z
      DOI: 10.1177/20406207221114673
      Issue No: Vol. 13 (2022)
       
  • Management of acquired, immune thrombocytopenic purpura (iTTP): beyond the
           acute phase

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      Authors: John Paul Westwood, Marie Scully
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Modern therapy for acute TTP has resulted in a dramatic improvement in outcomes, with the combination of plasma exchange, immunosuppression, and caplacizumab being associated with>90% survival rates following an acute episode. TTP is no longer associated with just the acute episode, but requires long-term follow-up. There remains significant morbidity associated with acute TTP, and many patients suffer marked neuropsychological sequelae, including impairment in cognitive functioning, affective disorders, and reduction in health-related quality of life measures. The focus of management beyond the acute phase centres on relapse prevention, via careful monitoring of patients and the use of either ad hoc or regular immunosuppressive therapies. The main therapy used is rituximab, but despite more limited evidence, other immunosuppressive therapies may be required to aim for normalisation of ADAMTS 13 activity. Follow-up with a reduction in ADAMTS 13 activity levels (ADAMTS 13 relapse), rituximab is central to normalisation of activity levels and prevention of a clinical relapse. Fundamental to elective therapy is the role of ADAMTS 13 activity monitoring, and impact of reduced ADAMTS13 activity on end organ damage. This review discusses monitoring and treatment strategy for long-term management of TTP, including the variety of therapies available to maintain remission, prevent relapse and a summary of a long-term treatment pathway.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-26T11:56:28Z
      DOI: 10.1177/20406207221112217
      Issue No: Vol. 13 (2022)
       
  • Major cardiac surgery with recombinant FIX Fc fusion protein replacement
           in hemophilia B: a case report

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      Authors: Jan-Paul Bohn, Anna Fiala, Sebastian Bachmann, Christian Irsara, Dominik Wolf, Clemens Feistritzer
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      The introduction of extended factor IX (FIX) products has significantly facilitated the treatment of hemophilia B patients. However, optimal perioperative management remains a topic of hot debate, particularly in surgeries with high bleeding risk. For the first time, we report here a patient with mild hemophilia B and degenerative aneurysms of aortic root and ascending aorta undergoing elective Bentall’s operation with full cardiopulmonary bypass, who was successfully managed with eftrenonacog alfa (Alprolix®), a recombinant FIX Fc fusion protein (rFIXFc). rFIXFc could safely be monitored using the Pathromtin SL aPTT-reagent. No significant bleeding was noted intraoperatively despite systemic heparinization as well as postoperatively. Higher doses of rFIXFc were inevitable to reach target FIX levels intraoperatively, whereas in the post-surgery setting stable FIX concentrations were maintained with only few rFIXFc injections facilitating fast wound healing and remobilization of the patient.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-26T11:55:15Z
      DOI: 10.1177/20406207221104595
      Issue No: Vol. 13 (2022)
       
  • Gene therapy in haemophilia: literature review and regional perspectives
           for Turkey

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      Authors: Kaan Kavaklı, Bülent Antmen, Vahap Okan, Fahri Şahin, Selin Aytaç, Can Balkan, Ergül Berber, Zühre Kaya, Alphan Küpesiz, Bülent Zülfikar
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Haemophilia is an X-linked lifelong congenital bleeding disorder that is caused by insufficient levels of factor VIII (FVIII; haemophilia A) or factor IX (FIX; haemophilia B) and characterized by spontaneous and trauma-related bleeding episodes. The cornerstone of the treatment, factor replacement, constitutes several difficulties, including frequent injections due to the short half-life of recombinant factors, intravenous administration and the risk of inhibitor development. While extended half-life factors and subcutaneous novel molecules enhanced the quality of life, initial successes with gene therapy offer a significant hope for cure. Although adeno-associated viral (AAV)-based gene therapy is one of the most emerging approaches for treatment of haemophilia, there are still challenges in vector immunogenicity, potency and efficacy, genotoxicity and persistence. As the approval for the first gene therapy product is coming closer, eligibility criteria for patient selection, multidisciplinary approach for optimal delivery and follow-up and development of new pricing policies and reimbursement models should be concerned. Therefore, this review addresses the unmet needs of current haemophilia treatment and explains the rationale and principles of gene therapy. Limitations and challenges are discussed from a global and national perspective and recommendations are provided to adopt the gene therapies faster and more sufficient for the haemophilia patients in developing countries like Turkey.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-23T12:38:57Z
      DOI: 10.1177/20406207221104591
      Issue No: Vol. 13 (2022)
       
  • Outcomes of patients with diffuse large B-cell and high-grade B-cell
           lymphomas with synchronous CNS and systemic involvement at diagnosis
           treated with high-dose methotrexate and R-CHOP: a single-center
           retrospective study

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      Authors: Megan Fleming, Ying Huang, Emily Dotson, David A. Bond, John Reneau, Narendranath Epperla, Lapo Alinari, Jonathan Brammer, Beth Christian, Robert A. Baiocchi, Kami Maddocks, Yazeed Sawalha
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:The optimal treatment of patients with systemic diffuse large B-cell (DLBCL) or high-grade B-cell (HGBL) lymphomas with synchronous central nervous system (CNS) involvement at diagnosis is not well defined. High-dose methotrexate administered concurrently with R-CHOP (RM-CHOP) is a commonly used regimen, but data on outcomes achieved with this regimen are limited.Objective:To report our experience with RM-CHOP in patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis.Design:A single-center retrospective analysis.Methods:We identified consecutive patients with systemic DLBCL or HGBL with synchronous CNS involvement at diagnosis who were treated with RM-CHOP from January 2012 to January 2021.Results:Fifty patients were included with a median age of 62 years; 82% had DLBCL (n = 41) and 18% had HGBL (n = 9). Treatment with RM-CHOP was followed by consolidative autologous hematopoietic cell transplantation in 14 patients (28%). The complete response (CR) rate following RM-CHOP was 62%. With a median follow-up of 40 months, the median progression-free (PFS) and overall (OS) survivals were 16 and 58 months, and the 2-year PFS and OS were 41% and 57%, respectively. The 2-year cumulative incidence of CNS progression/relapse was 29%. Outcomes were particularly poor in HGBL, with median PFS and OS of 6 and 7 months, compared with median PFS and OS of 22 months and not reached in DLBCL, respectively. The outcomes of patients with relapsed/progressive disease were poor, with only 63% of patients receiving subsequent treatments and only 21% achieving CR to next subsequent treatment. Most patients (58%) with disease relapse/progression had CNS involvement which was associated with very poor outcomes (median OS of 2 months).Conclusion:CNS involvement in aggressive B-cell non-Hodgkin lymphoma at diagnosis dictates clinical outcomes and requires more effective treatment options.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-23T12:06:06Z
      DOI: 10.1177/20406207221112900
      Issue No: Vol. 13 (2022)
       
  • The development of pevonedistat in myelodysplastic syndrome (MDS) and
           acute myeloid leukemia (AML): hope or hype'

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      Authors: Anson Snow, Joshua F. Zeidner
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder clinically defined by cytopenias, bone marrow failure, and an increased risk of progressing to acute myeloid leukemia (AML). Traditionally, first-line treatment for patients with higher-risk MDS has been hypomethylating agents (HMAs). However, these agents have modest clinical activity as single agents. A one-size-fits-all treatment paradigm is insufficient for such a heterogeneous disease in the modern era of precision medicine. Several new agents have been developed for MDS with the hopes of improving clinical outcomes and survival. Pevonedistat is a first-in-class, novel inhibitor of neuronal precursor cell-expressed developmentally down-regulated protein-8 (NEDD8) activating enzyme (NAE) blocking the neddylation pathway leading to downstream effects on the ubiquitin–proteosome pathway. Pevonedistat ultimately leads to apoptosis and inhibition of the cell cycle in cancer cells. Studies have demonstrated the safety profile of pevonedistat, leading to the development of multiple trials investigating combination strategies with pevonedistat in MDS and AML. In this review, we summarize the preclinical and clinical rationale for pevonedistat in MDS and AML, review the clinical data of this agent alone and in combination with HMAs to date, and highlight potential future directions for this agent in myeloid malignancies.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-22T12:20:17Z
      DOI: 10.1177/20406207221112899
      Issue No: Vol. 13 (2022)
       
  • Toxicity management strategies for next-generation novel therapeutics in
           multiple myeloma

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      Authors: Mary Steinbach, Kelley Julian, Brian McClune, Douglas W. Sborov
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      The therapeutic options available for patients with multiple myeloma have greatly expanded over the past decade and incorporating these novel agents into routine clinical practice has significantly improved outcomes. The next generation of therapeutics is available for relapsed and refractory patients either as standard of care or in clinical trial, and these drugs represent a generational paradigm shift. Patients now have access to a multitude of novel immunotherapeutics, including monoclonal antibodies, an antibody–drug conjugate, chimeric antigen receptor T-cells (CAR-T), and bispecific T-cell redirecting antibodies, and novel oral therapies including selinexor (selective inhibitor of nuclear export) and venetoclax (bcl-2 inhibitor). While these drugs have the potential to be highly efficacious in certain subsets of patients when used as single agents or in combination regimens, they are each associated with unique toxicity profiles. It is imperative to understand these potential adverse events to ensure patient safety. Appropriate supportive care management is paramount to maximize drug exposure and therapeutic efficacy. The following review focuses its discussion on drugs and combination regimens that are currently FDA-approved and those that continue to be investigated in clinical trials, highlights the clinically relevant toxicity profiles for each of the different agents, and provides practical considerations for the treatment team.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-07-15T11:12:37Z
      DOI: 10.1177/20406207221100659
      Issue No: Vol. 13 (2022)
       
  • Current options and future perspectives in the treatment of patients with
           relapsed/refractory diffuse large B-cell lymphoma

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      Authors: Fabian Frontzek, Imke Karsten, Norbert Schmitz, Georg Lenz
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of aggressive lymphoma. Depending on individual risk factors, roughly 60–65% of patients can be cured by chemoimmunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, patients with primary refractory disease or relapse (R/R) after an initial response are still characterized by poor outcome. Until now, transplant-eligible R/R DLBCL patients are treated with intensive salvage regimens followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) which, however, only cures a limited number of patients. It is most likely that in patients with early relapse after chemoimmunotherapy, chimeric antigen receptor (CAR) T-cells will replace high-dose chemotherapy and ASCT. So far, transplant-ineligible patients have mostly been treated in palliative intent. Recently, a plethora of novel agents comprising new monoclonal antibodies, antibody drug conjugates (ADC), bispecific antibodies, and CAR T-cells have emerged and have significantly improved outcome of patients with R/R DLBCL. In this review, we summarize our current knowledge on the usage of novel drugs and approaches for the treatment of patients with R/R DLBCL.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-06-28T11:35:02Z
      DOI: 10.1177/20406207221103321
      Issue No: Vol. 13 (2022)
       
  • Real-world effectiveness and safety analysis of
           carfilzomib–lenalidomide–dexamethasone and carfilzomib–dexamethasone
           in relapsed/refractory multiple myeloma: a multicenter retrospective
           analysis

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      Authors: Yoshiyuki Onda, Junya Kanda, Hitomi Kaneko, Yuji Shimura, Shin-ichi Fuchida, Aya Nakaya, Tomoki Itou, Ryosuke Yamamura, Hirokazu Tanaka, Hirohiko Shibayama, Yutaka Shimazu, Hitoji Uchiyama, Satoshi Yoshihara, Yoko Adachi, Mitsuhiro Matsuda, Hitoshi Hanamoto, Nobuhiko Uoshima, Satoru Kosugi, Kensuke Ohta, Hideo Yagi, Yuzuru Kanakura, Itaru Matsumura, Masayuki Hino, Shosaku Nomura, Chihiro Shimazaki, Akifumi Takaori-Kondo, Junya Kuroda
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Little is known about the real-world survival benefits and safety profiles of carfilzomib–lenalidomide–dexamethasone (KRd) and carfilzomib–dexamethasone (Kd).Methods:We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database.Results:A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia.Conclusion:Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-06-24T12:02:13Z
      DOI: 10.1177/20406207221104584
      Issue No: Vol. 13 (2022)
       
  • Expression of γ-globin genes in β-thalassemia patients treated with
           sirolimus: results from a pilot clinical trial (Sirthalaclin)

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      Authors: Cristina Zuccato, Lucia Carmela Cosenza, Matteo Zurlo, Jessica Gasparello, Chiara Papi, Elisabetta D’Aversa, Giulia Breveglieri, Ilaria Lampronti, Alessia Finotti, Monica Borgatti, Chiara Scapoli, Alice Stievano, Monica Fortini, Eric Ramazzotti, Nicola Marchetti, Marco Prosdocimi, Maria Rita Gamberini, Roberto Gambari
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:β-thalassemia is caused by autosomal mutations in the β-globin gene, which induce the absence or low-level synthesis of β-globin in erythroid cells. It is widely accepted that a high production of fetal hemoglobin (HbF) is beneficial for patients with β-thalassemia. Sirolimus, also known as rapamycin, is a lipophilic macrolide isolated from a strain of Streptomyces hygroscopicus that serves as a strong HbF inducer in vitro and in vivo. In this study, we report biochemical, molecular, and clinical results of a sirolimus-based NCT03877809 clinical trial (a personalized medicine approach for β-thalassemia transfusion-dependent patients: testing sirolimus in a first pilot clinical trial, Sirthalaclin).Methods:Accumulation of γ-globin mRNA was analyzed using reverse-transcription quantitative polymerase chain reaction (PCR), while the hemoglobin pattern was analyzed using high-performance liquid chromatography (HPLC). The immunophenotype was analyzed using a fluorescence-activated cell sorter (FACS), with antibodies against CD3, CD4, CD8, CD14, CD19, CD25 (for analysis of peripheral blood mononuclear cells), or CD71 and CD235a (for analysis of in vitro cultured erythroid precursors).Results:The results were obtained in eight patients with the β+/β+ and β+/β0 genotypes, who were treated with a starting dosage of 1 mg/day sirolimus for 24–48 weeks. The first finding of this study was that the expression of γ-globin mRNA increased in the blood and erythroid precursor cells isolated from β-thalassemia patients treated with low-dose sirolimus. This trial also led to the important finding that sirolimus influences erythropoiesis and reduces biochemical markers associated with ineffective erythropoiesis (excess free α-globin chains, bilirubin, soluble transferrin receptor, and ferritin). A decrease in the transfusion demand index was observed in most (7/8) of the patients. The drug was well tolerated, with minor effects on the immunophenotype, and an only side effect of frequently occurring stomatitis.Conclusion:The data obtained indicate that low doses of sirolimus modify hematopoiesis and induce increased expression of γ-globin genes in a subset of patients with β-thalassemia. Further clinical trials are warranted, possibly including testing of the drug in patients with less severe forms of the disease and exploring combination therapies.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-06-21T07:08:45Z
      DOI: 10.1177/20406207221100648
      Issue No: Vol. 13 (2022)
       
  • Azacitidine and donor lymphocytes infusions in acute myeloid leukemia and
           myelodysplastic syndrome relapsed after allogeneic hematopoietic stem cell
           transplantation from alternative donors

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      Authors: Carmine Liberatore, Maria Teresa Lupo Stanghellini, Francesca Lorentino, Luca Vago, Matteo Giovanni Carrabba, Raffaella Greco, Sarah Marktel, Andrea Assanelli, Francesca Farina, Consuelo Corti, Massimo Bernardi, Jacopo Peccatori, Katja Sockel, Jan Moritz Middeke, Johannes Schetelig, Anika Bergmann, Christina Rautenberg, Fabio Ciceri, Martin Bornhäuser, Thomas Schroeder, Friedrich Stölzel
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:Azacitidine (AZA) either single-agent or with donor lymphocytes infusions (DLI) has been used as a salvage treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) relapsing after allogeneic hematopoietic stem cell transplantation (HSCT). To date, the majority of data come from patients relapsed after HSCT from full-matched donors.Methods:We report a multicenter, collaborative, retrospective analysis of 71 patients with hematologic (n = 40, 56%) and molecular relapse (n = 31, 44%) of myeloid neoplasms after HSCT from alternative donors (mismatched unrelated, n = 39, 55%; haploidentical, n = 29, 41%) consecutively treated at three European centers with AZA ± DLI.Results:Median time from HSCT to relapse was 9 months. Additional DLI were given to 33 patients (46%). After a median of four cycles, overall response rate (ORR) was 49% and complete response (CR) rate was 38%. CR lasted for a median of 17 months (range 5–89 months). Median follow-up in the entire cohort was 11 months (range 1–115 months). Event-free survival (EFS) and overall survival (OS) at 1 year were 26% and 53%, respectively. Treatment of molecular relapse granted higher CR rate (65% versus 15%; p = 0.0001), 1-year EFS (43% versus 13%; p = 0.006), and 1-year OS (79% versus 34%; p 
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-06-18T06:18:30Z
      DOI: 10.1177/20406207221090882
      Issue No: Vol. 13 (2022)
       
  • The potential of pirtobrutinib in multiple B-cell malignancies

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      Authors: Jeffrey L. Jensen, Anthony R. Mato, Camila Pena, Lindsey E. Roeker, Catherine C. Coombs
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Bruton’s tyrosine kinase (BTK) is a critical downstream signaling element from the B-cell receptor (BCR) that has been effectively inhibited in B-cell cancers by irreversible, covalent inhibitors including ibrutinib and acalabrutinib. All FDA-approved covalent BTK inhibitors rely on binding to the cysteine 481 (C481) amino acid within the active site of BTK, thus rendering it inert. While covalent BTK inhibitors have been very successful in multiple B-cell malignancies, improving both overall survival and progression-free survival relative to chemoimmunotherapy in phase 3 trials, they can be limited by intolerance and disease progression. Pirtobrutinib is a novel, highly selective, and non-covalent BTK inhibitor that binds independently of C481, and in a recent, first-in-human phase 1/2 clinical trial was shown to be extremely well tolerated and lead to remissions in relapsed/refractory patients with multiple B-cell malignancies. Here, we review the pharmacologic rationale for pursuing non-covalent BTK inhibitors, the clinical need for such inhibitors, existing safety, and resistance mechanism data for pirtobrutinib, and the forthcoming clinical trials that seek to define the clinical utility of pirtobrutinib, which has the potential to fulfill multiple areas of unmet clinical need for patients with B-cell malignancies.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-06-17T06:25:56Z
      DOI: 10.1177/20406207221101697
      Issue No: Vol. 13 (2022)
       
  • The importance of terminal complement inhibition in paroxysmal nocturnal
           hemoglobinuria

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      Authors: Austin G. Kulasekararaj, Robert A. Brodsky, Jun-ichi Nishimura, Christopher J. Patriquin, Hubert Schrezenmeier
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic hematologic disorder associated with inappropriate terminal complement activity on blood cells that can result in intravascular hemolysis (IVH), thromboembolic events (TEs), and organ damage. Untreated individuals with PNH have an increased risk of morbidity and mortality. Patients with PNH experiencing IVH often present with an elevated lactate dehydrogenase (LDH; ⩾ 1.5 × the upper limit of normal) level which is associated with a significantly higher risk of TEs, one of the leading causes of death in PNH. LDH is therefore used as a biomarker for IVH in PNH. The main objective of PNH treatment should therefore be prevention of morbidity and mortality due to terminal complement activation, with the aim of improving patient outcomes. Approval of the first terminal complement inhibitor, eculizumab, greatly changed the treatment landscape of PNH by giving patients an effective therapy and demonstrated the critical role of terminal complement and the possibility of modulating it therapeutically. The current mainstays of treatment for PNH are the terminal complement component 5 (C5) inhibitors, eculizumab and ravulizumab, which have shown efficacy in controlling terminal complement-mediated IVH, reducing TEs and organ damage, and improving health-related quality of life in patients with PNH since their approval by the United States Food and Drug Administration in 2007 and 2018, respectively. Moreover, the use of eculizumab has been shown to reduce mortality due to PNH. More recently, interest has arisen in developing additional complement inhibitors with different modes of administration and therapeutics targeting other components of the complement cascade. This review focuses on the pathophysiology of clinical complications in PNH and explores why sustained inhibition of terminal complement activity through the use of complement inhibitors is essential for the management of patients with this chronic and debilitating disease.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-31T06:24:58Z
      DOI: 10.1177/20406207221091046
      Issue No: Vol. 13 (2022)
       
  • Zanubrutinib in lymphoproliferative disorders: a comprehensive review

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      Authors: Javier Muñoz, Yucai Wang, Preetesh Jain, Michael Wang
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      The availability of Bruton tyrosine kinase (BTK) inhibitors has brought about a paradigm shift in the treatment of patients with B-cell lymphomas and chronic lymphocytic leukemia. BTK was clinically validated as a target by the efficacy of the first-in-class inhibitor ibrutinib. The extended survival conferred by BTK inhibitors has brought long-term tolerability to the foreground. To minimize toxicities thought to be attributable to off-target kinase inhibition, a next generation of BTK inhibitors with greater selectivity was developed. In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenström macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20–based therapy. Because few head-to-head comparative trials of BTK inhibitors have so far been reported, no BTK ‘inhibitor of choice’ can be identified. Zanubrutinib has promising efficacy in its approved indications and appears to have reduced cardiac toxicities, particularly atrial fibrillation, which may influence the choice of BTK inhibitor treatment by prescribers. Further studies are needed to inform on optimal treatment sequencing of zanubrutinib and its combination with other agents. Here, we summarize existing clinical evidence for its efficacy and safety in mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other B-lymphoproliferative indications.Plain Language SummaryZanubrutinib is a drug that was shown to effectively treat cancer of B cells without causing excessive serious side effectsPatients with certain B-cell malignancies (cancers of white blood cells) benefit from treatment with Bruton tyrosine kinase (BTK) inhibitors, drugs that block the BTK protein and keep cancer from growing and spreading. Patients experience extended survival with ibrutinib, the first-generation BTK inhibitor approved by US Food and Drug Administration (FDA); however, one in five patients quit treatment because of harmful side effects. Ibrutinib-related side effects such as increased risk of bleeding, atrial fibrillation (abnormal heart rhythm), and high blood pressure are thought to be caused by ibrutinib blocking other proteins besides the intended target protein BTK. To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib. Results of clinical studies on zanubrutinib treatment appear promising in patients with several types of B-cell malignancies, including mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia, and small lymphocytic lymphoma. There are not yet enough clinical data to determine which BTK inhibitor is most effective in treating B-cell malignancies without causing harmful side effects. Early data from the phase 3 ALPINE clinical study suggest that zanubrutinib works better than ibrutinib, and fewer patients experience side effects and quit treatment. Zanubrutinib is currently approved for use for treatment of adult patients with MCL who have received at least one prior therapy, for adults with WM, and for adults with MZL who have received at least one anti-CD20–based therapy.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-28T05:26:04Z
      DOI: 10.1177/20406207221093980
      Issue No: Vol. 13 (2022)
       
  • Relapsed acute lymphoblastic leukaemia after allogeneic stem cell
           transplantation: a therapeutic dilemma challenging the armamentarium of
           immunotherapies currently available (case reports)

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      Authors: Fiona Poyer, Anna Füreder, Wolfgang Holter, Christina Peters, Heidrun Boztug, Michael Dworzak, Gernot Engstler, Waltraud Friesenbichler, Stefan Köhrer, Roswitha Lüftinger, Leila Ronceray, Volker Witt, Herbert Pichler, Andishe Attarbaschi
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      While survival rates in paediatric acute lymphoblastic leukaemia (ALL) nowadays exceed 90%, systemic ALL relapse, especially after haemopoietic stem cell transplantation (HSCT), is associated with a poor outcome. As there is currently no standardized treatment for this situation, individualized treatment is often pursued. Exemplified by two clinical scenarios, the aim of this article is to highlight the challenge for treating physicians to find a customized treatment strategy integrating the role of conventional chemotherapy, immunotherapeutic approaches and second allogeneic HSCT. Case 1 describes a 2-year-old girl with an early isolated bone marrow relapse of an infant KMT2A-rearranged B-cell precursor ALL after allogeneic HSCT. After bridging chemotherapy and lymphodepleting chemotherapy, chimeric antigen receptor (CAR) T-cells (tisagenlecleucel) were administered for remission induction, followed by a second HSCT from the 9/10 human leukocyte antigen (HLA)-matched mother. Case 2 describes a 16-year-old girl with a late, isolated bone marrow relapse of B-cell precursor ALL after allogeneic HSCT who experienced severe treatment toxicities including stage IV renal insufficiency. After dose-reduced bridging chemotherapy, CAR T-cells (tisagenlecleucel) were administered for remission induction despite a CD19- clone without prior lymphodepletion due to enhanced persisting toxicity. This was followed by a second allogeneic HSCT from the haploidentical mother. While patient 2 relapsed around Day + 180 after the second HSCT, patient 1 is still in complete remission>360 days after the second HSCT. Both cases demonstrate the challenges associated with systemic ALL relapse after first allogeneic HSCT, including chemotherapy-resistant disease and persisting organ damage inflicted by previous therapy. Immunotherapeutic approaches, such as CAR T-cells, can induce remission and enable a second allogeneic HSCT. However, optimal therapy for systemic ALL relapse after first HSCT remains to be defined.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-24T05:29:33Z
      DOI: 10.1177/20406207221099468
      Issue No: Vol. 13 (2022)
       
  • Safety and immunogenicity of the BNT162b2 mRNA Covid-19 vaccine in
           patients with chronic lymphocytic leukemia: a prospective study

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      Authors: Panagiotis T. Diamantopoulos, Christos Stafylidis, Dimitra Vlachopoulou, Christina-Nefeli Kontandreopoulou, Nefeli Giannakopoulou, Maria Vardaka, Anthi Mpouhla, Elpida Mastrogianni, Eleni Variami, Athanasios Galanopoulos, Vasiliki Pappa, Mina Psichogiou, Angelos Hatzakis, Nora-Athina Viniou
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:Immunization of patients with chronic lymphocytic leukemia (CLL) with vaccines against several infectious diseases has proven insufficient. Data on seroconversion of patients with CLL after vaccination against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are still young, but accumulating evidence shows low seroconversion rates.Methods:We conducted a prospective, noninterventional study evaluating the safety and immunogenicity of two doses of the BNT162b2 mRNA Covid-19 vaccine, administered 21 days apart in consecutive adult patients with CLL. Patients vaccinated with other vaccines against SARS-CoV-2, with a history of confirmed Coronavirus Disease 19 (COVID-19), with known human immunodeficiency virus infection, or with an inability to provide written informed consent were excluded. Sera were tested before the first and after the second dose of the vaccine for anti-SARS-CoV-2 receptor binding domain (RBD) spike protein IgG (anti-RBD), using the Abbott SARS-CoV-2 IgG II Quant assay (Abbott Laboratories, Abbott Park, IL, USA), with a cutoff value for seroconversion at 50 AU/ml.Results:Sixty-one patients (28 males/33 females) with CLL, with a median age of 61 years, were included in the study. The majority of the patients (82.0%) were lower (0–2) stage per the RAI staging system. The seroconversion rate at 14 days after the second dose was 45% and was correlated with RAI stage (0–2 versus 3–4; 51.0% versus 18.3%, p = 0.047), the treatment status (treatment naïve, previously treated, or actively treated patients; 63.0% versus 40.0% versus 26.1%, respectively, p = 0.031), the number of previous treatment lines (0–2 versus>2; 55.3% versus 8.3%, p = 0.004), and the platelet count of the patients (over or under 100 × 109/L; 52.9% versus 10.0%, p = 0.015). Moreover, there was a positive linear relationship between the antibody titers and the gamma-globulin levels (r = 0.182, p = 0.046) and platelet count (r = 0.277, p = 0.002). Finally, patients actively treated with venetoclax had higher antibody titers than those treated with ibrutinib (15.8 AU/ml versus 0.0 AU/ml, p = 0.047). No safety issues were identified while the emergence of adverse events was not correlated with immunogenicity.Discussion:This study confirms results from previous studies on the low seroconversion rates in patients with CLL vaccinated with the BNT162b2 mRNA Covid-19 vaccine and on the detrimental effect of advanced disease and multiple treatment lines on seroconversion, while it is suggested that treatment with venetoclax may offer a chance for higher antibody titers, suggesting a treatment strategy change during the pandemic provided that this result is confirmed by larger studies specifically designed to address this issue.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-23T10:56:12Z
      DOI: 10.1177/20406207221090150
      Issue No: Vol. 13 (2022)
       
  • Efficacy and safety of cyclosporine A treatment in autoimmune cytopenias:
           the experience of two Italian reference centers

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      Authors: Bruno Fattizzo, Silvia Cantoni, Juri Alessandro Giannotta, Laura Bandiera, Rachele Zavaglia, Marta Bortolotti, Wilma Barcellini
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) show good responses to frontline steroids. About two-third of cases relapse and require second-line treatment, including rituximab, mainly effective in AIHA, and thrombopoietin-receptor agonists (TPO-RAs) in ITP, while the use of splenectomy progressively decreased due to concerns for infectious/thrombotic complications. For those failing second line, immunosuppressants may be considered.Objectives:The aim of this study was to evaluate the efficacy of cyclosporine treatment in patients with ITP and AIHA.Design:In this retrospective study, we evaluated the efficacy and safety of cyclosporine A (CyA) in ITP (N = 29) and AIHA (N = 10) patients followed at two reference centers in Milan, Italy.Methods:Responses were classified as partial [Hb > 10 or at least 2 g/dl increase from baseline, platelets (PLT) > 30 × 109/l with at least doubling from baseline] and complete (Hb > 12 g/dl or PLT > 100 × 109/l) and evaluated at 3, 6, and 12 months. Treatment emergent adverse events were also registered.Results:The median time from diagnosis to CyA was 35 months (3–293), and patients had required a median of 4 (1–8) previous therapy lines. Median duration of CyA was 28 (2–140) months and responses were achieved in 86% of ITP and 50% of AIHA subjects. Responders could reduce or discontinue concomitant treatment and resolved PLT fluctuations on TPO-RA. CyA was generally well tolerated, and only two serious infectious complications in elderly patients on concomitant steroids suggesting caution in this patient population.Conclusion:CyA may be advisable in ITP, which is not well controlled under TPO-RA, and in AIHA failing rituximab, particularly if ineligible in clinical trial.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-14T08:23:11Z
      DOI: 10.1177/20406207221097780
      Issue No: Vol. 13 (2022)
       
  • The role of surveillance computed tomography in patients with follicular
           lymphoma

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      Authors: Shunsuke Hatta, Suguru Fukuhara, Takahiro Fujino, Yo Saito, Yuta Ito, Shinichi Makita, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Masahiko Kusumoto, Koji Izutsu
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:Surveillance computed tomography (CT) is performed during the follow-up of patients with lymphoma who have completed initial therapy. However, studies on the clinical benefit of surveillance CT for patients with incurable subtypes, such as follicular lymphoma (FL), are limited. This study aimed to evaluate the value of surveillance CT for patients with FL after achieving the first complete response (CR) or CR unconfirmed in the rituximab era.Methods:We retrospectively reviewed the medical records of patients with FL who achieved CR with first-line treatment between 2000 and 2016 at our institution. In patients who experienced first relapse, we examined the patient’s clinical characteristics at the time of relapse, subsequent therapies, and post-relapse survival, based on the method of relapse detection.Results:Of the 248 patients who achieved CR after initial therapy, 109 had a relapse, with a median follow-up of 11 years; 100 were enrolled into this study. Relapse was detected by surveillance CT in 61 patients (surveillance CT group) and by means other than surveillance CT, such as the presence of patient-reported symptoms, physical findings, and blood work-up abnormalities (non-surveillance CT group), in 39 patients. There was no significant difference in the patients’ characteristics at the time of relapse between the two groups, except for a higher incidence of extranodal involvement in the non-surveillance CT group. The method of relapse detection did not affect therapeutic selection after relapse and post-relapse survival. In this study, 86.8% of the 38 patients who relapsed with only deep lesions, such as mesenteric or retroperitoneal lymph nodes, had surveillance CT-detected relapse.Conclusion:Surveillance CT did not show any clinical benefit for patients with FL in CR; however, it might lead to early detection of relapse in cases of deep lesions that cannot be identified without imaging.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-14T07:25:55Z
      DOI: 10.1177/20406207221095963
      Issue No: Vol. 13 (2022)
       
  • Pomalidomide- and dexamethasone-based regimens in the treatment of
           refractory/relapsed multiple myeloma

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      Authors: Despina Fotiou, Maria Gavriatopoulou, Evangelos Terpos, Meletios A. Dimopoulos
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Pomalidomide is a potent immunomodulatory agent that is currently a standard of care backbone for the treatment of multiple myeloma (MM) patients in the relapsed/refractory setting after exposure to lenalidomide and a proteasome inhibitor. The present review addresses current knowledge regarding the clinical use of pomalidomide in relapsed myeloma patients. Pomalidomide has direct myeloma cell tumoricidal effects by activating proteasomal degradation of Ikaros and Aiolos transcription factors and also indirect effects by modulation of immune responses, interaction with bone marrow stromal cells, and inhibition of angiogenesis. It is approved by regulatory authorities as doublet combination with dexamethasone but four more triplets are also approved for this setting. Many ongoing trials are evaluating the pomalidomide–dexamethasone backbone with newer anti-myeloma class agents or in quadruplet combinations. Pomalidomide–dexamethasone is currently one of the powerful tools available for use in the relapsed/refractory MM setting. Insights into the synergistic immunomodulatory effects of pomalidomide and other anti-myeloma agents and the mechanisms that overcome clonal resistance will potentially allow targeted use of triplet combinations at each relapse.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-05-13T09:02:22Z
      DOI: 10.1177/20406207221090089
      Issue No: Vol. 13 (2022)
       
  • Prednisone plus IVIg compared with prednisone or IVIg for immune
           thrombocytopenia in pregnancy: a national retrospective cohort study

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      Authors: Xiao-Lu Zhu, Ru Feng, Qiu-Sha Huang, Mei-Ying Liang, Ming Jiang, Hui Liu, Yi Liu, Hong-Xia Yao, Lei Zhang, Shen-Xian Qian, Tong-Hua Yang, Jing-Yu Zhang, Xu-Liang Shen, Lin-Hua Yang, Jian-Da Hu, Ren-Wei Huang, Zhong-Xing Jiang, Jing-Wen Wang, Hong-Yu Zhang, Zhen Xiao, Si-Yan Zhan, Hui-Xin Liu, Xing-Lin Wang, Ying-Jun Chang, Yu Wang, Yuan Kong, Lan-Ping Xu, Kai-Yan Liu, Xiao-Hong Zhang, Cheng-Hong Yin, Yue-Ying Li, Qian-Fei Wang, Jian-Liu Wang, Xiao-Jun Huang, Xiao-Hui Zhang
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP).Methods:Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone.Results:Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p  
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-30T04:11:50Z
      DOI: 10.1177/20406207221095226
      Issue No: Vol. 13 (2022)
       
  • Advancing the standard: venetoclax combined with intensive induction and
           consolidation therapy for acute myeloid leukemia

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      Authors: Curtis A. Lachowiez, Himachandana Atluri, Courtney D. DiNardo
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      The B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with lower-intensity therapy is an efficacious treatment for acute myeloid leukemia (AML). VEN in combination with the hypomethylating agent azacitidine improved rates of response and measurable residual disease (MRD)-negative remissions in addition to overall survival in the pivotal phase 3 VIALE-A trial compared with azacitidine monotherapy and has since emerged as the current standard of care in older or unfit patients with AML. In younger, fit patients with AML, intensive induction and consolidation chemotherapy (IC) is commonly employed as frontline therapy; however, relapse remains the principal cause of treatment failure in approximately 30–40% of patients. Improved IC regimens that increase MRD-negative response rates, result in durable remissions, and enable transition to curative allogeneic hematopoietic stem cell transplantation in appropriate patients remain an area of active inquiry. Preliminary results from trials investigating the combination of VEN with IC have reported promising findings to date, with composite complete remission and MRD-negative remission rates of approximately 89–94% and 82–93%, respectively, correlating with improved 12-month event-free and overall survival compared to historical outcomes with IC. Herein, we discuss ongoing trials investigating VEN in combination with IC in addition to outcomes within specific molecularly defined subgroups; review the molecular mechanisms of sensitivity and resistance to VEN, and highlight future combinations of VEN with novel targeted therapies for the treatment of AML.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-29T08:54:16Z
      DOI: 10.1177/20406207221093964
      Issue No: Vol. 13 (2022)
       
  • Treatment paradigm in Waldenström macroglobulinemia: frontline
           therapy and beyond

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      Authors: Saurabh Zanwar, Jithma P. Abeykoon
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Waldenström macroglobulinemia (WM) is an indolent lymphoplasmacytic lymphoma. Recent strides made in the genomic profiling of patients with WM have led to the identification of many novel therapeutic targets. Patients with WM can present with asymptomatic disease and not all patients require treatment. When criteria for initiating systemic therapy are met, the choice of therapy depends on the tumor genotype (MYD88 and CXCR4 mutation status), patient preference (fixed versus continuous duration therapy, oral versus intravenous route, cost), associated medical comorbidities, and adverse effect profile of the treatment. In the absence of head-to-head comparison between chemoimmunotherapy and Bruton’s tyrosine kinase inhibitors in otherwise fit patients with a MYD88L265P mutation, our preference is fixed duration therapy with four to six cycles of chemoimmunotherapy with bendamustine–rituximab. In this review, we discuss the role of MYD88 and CXCR4 mutation in treatment selection, and current data for frontline and salvage treatment options in patients with WM.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-29T08:49:01Z
      DOI: 10.1177/20406207221093962
      Issue No: Vol. 13 (2022)
       
  • The impact of bortezomib-based induction in newly diagnosed multiple
           myeloma with chromosome 1q21 gain

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      Authors: Hoi Ki Karen Tang, Chi Yeung Fung, Gareth J. Morgan, Shaji Kumar, Lisa Siu, Ho Wan Alvin Ip, Sze Fai Yip, Ka Ngai Harry Lau, Chi Kuen Lau, Harold Lee, Kwan Hung Leung, Bonnie Kho, Howard Wong, Cheong Ngai, Yu Yan Hwang, Joycelyn Sim, Yok Lam Kwong, Chor Sang Chim
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:Bortezomib has been reported to favourably impact the outcomes of t(4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown.Methods:To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t(14;16), t(4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells.Results:+1q identified in 167 (66.8%) and associated with t(4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t(4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069).Conclusion:+1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-18T07:12:17Z
      DOI: 10.1177/20406207221082043
      Issue No: Vol. 13 (2022)
       
  • Updates in hairy cell leukemia (HCL) and variant-type HCL (HCL-V):
           rationale for targeted treatments with a focus on ibrutinib

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      Authors: Jérôme Paillassa, Firas Safa, Xavier Troussard
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Hairy cell leukemia (HCL) and HCL-like disorders such as hairy cell leukemia variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL) are rare indolent B-cell malignancies. Purine analogs (PNAs), alone or in association with rituximab (R), are the standard of care for HCL in the first-line setting. However, PNAs are toxic and patients may become resistant to these drugs. Therefore, new therapeutic strategies are needed. Several recent in vitro studies highlighted the importance of the interactions between HCL cells and their microenvironment, in particular with bone marrow stromal cells, endothelial cells, and the extracellular matrix. In these interactions, chemokine receptors and adhesion molecules play a major role. Moreover, the importance of signaling pathways, like BRAF, BCR, and CXCR4 has been underlined. Bruton’s tyrosine kinase (BTK) is a fundamental signal transmitter of BCR and CXCR4 in HCL. Preclinical and recent clinical data showed an efficacy of ibrutinib, a BTK inhibitor (BTKi), in HCL and HCL-V. These promising results joined those of other emerging drugs like BRAF or MEK inhibitors and anti-CD22 immunotoxins.Plain Language SummaryBruton’s tyrosine kinase (BTK) inhibitors (BTKi) in hairy cell leukemia (HCL) and variant-type HCLThe treatment of hairy cell leukemia (HCL) has changed significantly in recent years. In the first-line settings, treatment with purine analogs (PNAs) with or without anti-CD20 monoclonal antibodies remains the gold standard in 2022. In relapsed/refractory HCL, other drugs are needed: BRAF inhibitors: vemurafenib monotherapy with or without rituximab or dabrafenib in combination with trametinib, an MEK inhibitor (MEKi), as well as the anti-CD22 antibody drug conjugate moxetumomab pasudotox.There are arguments for the use of Bruton’s tyrosine kinase inhibitors (BTKi). Ibrutinib was recently tested in a multisite phase 2 study in 37 patients with either HCL (28 patients: 76%) or HCL-V (nine patients: 24%) including two who were previously untreated. Patients received single-agent ibrutinib at 420 mg daily (24 patients) or 840 mg daily (13 patients) until disease progression or unacceptable toxicity. The overall response rate (ORR) at 32 weeks was 24%, increasing to 36% at 48 weeks and reaching 54% at any time since starting ibrutinib. Seven patients achieved a complete response (CR) as the best response at any time on study, while 13 patients had a partial response (PR) and 10 patients had stable disease (SD). Interestingly, the response rate was not statistically different between HCL and HCL-V patients, suggesting that ibrutinib could be an option in both entities. The estimated 36-month progression-free survival (PFS) was 73% and the estimated 36-month overall survival (OS) was 85%, with no differences between HCL and HCL-V. The frequency of cardiovascular grade 1–2 adverse events (AEs) was 16% for atrial fibrillation; 3% for atrial flutter; 32% for hypertension; and 0%, 3%, and 11%, respectively, for grade ⩾ 3 AEs. Unlike in chronic lymphocytic leukemia (CLL), where the mechanism of action of ibrutinib is well known, the mechanism of action of ibrutinib in HCL appears to be unclear. No mutations were identified in patients with progressive disease, suggesting that the mechanisms of resistance could be different between HCL and CLL. The BTKi that are not yet approved are challenged by the new other targeted treatments.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-13T01:30:16Z
      DOI: 10.1177/20406207221090886
      Issue No: Vol. 13 (2022)
       
  • International consensus recommendations on the management of people with
           haemophilia B

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      Authors: Daniel P. Hart, Davide Matino, Jan Astermark, Gerard Dolan, Roseline d’Oiron, Cédric Hermans, Victor Jiménez-Yuste, Adriana Linares, Tadashi Matsushita, Simon McRae, Margareth C. Ozelo, Sean Platton, Darrel Stafford, Robert F. Sidonio, Andreas Tiede
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Haemophilia B is a rare X-linked genetic deficiency of coagulation factor IX (FIX) that, if untreated, can cause recurrent and disabling bleeding, potentially leading to severe arthropathy and/or life-threatening haemorrhage. Recent decades have brought significant improvements in haemophilia B management, including the advent of recombinant FIX and extended half-life FIX. This therapeutic landscape continues to evolve with several non-factor replacement therapies and gene therapies under investigation. Given the rarity of haemophilia B, the evidence base and clinical experience on which to establish clinical guidelines are relatively sparse and are further challenged by features that are distinct from haemophilia A, precluding extrapolation of existing haemophilia A guidelines. Due to the paucity of formal haemophilia B-specific clinical guidance, an international Author Group was convened to develop a clinical practice framework. The group comprised 15 haematology specialists from Europe, Australia, Japan, Latin America and North America, covering adult and paediatric haematology, laboratory medicine and biomedical science. A hybrid approach combining a systematic review of haemophilia B literature with discussion of clinical experience utilized a modified Delphi format to develop a comprehensive set of clinical recommendations. This approach resulted in 29 recommendations for the clinical management of haemophilia B across five topics, including product treatment choice, therapeutic agent laboratory monitoring, pharmacokinetics considerations, inhibitor management and preparing for gene therapy. It is anticipated that this clinical practice framework will complement existing guidelines in the management of people with haemophilia B in routine clinical practice and could be adapted and applied across different regions and countries.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-02T12:00:01Z
      DOI: 10.1177/20406207221085202
      Issue No: Vol. 13 (2022)
       
  • An overview of treatment options for patients with relapsed/refractory
           multiple myeloma and renal impairment

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      Authors: Meletios A. Dimopoulos, Joseph Mikhael, Evangelos Terpos, Xavier Leleu, Philippe Moreau, Joan Bladé, Jin Seok Kim, Keith Stockerl-Goldstein, Paul G. Richardson
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Renal impairment (RI) is a relatively common complication of multiple myeloma, which increases in frequency as disease becomes more advanced and recovery of renal function becomes less likely as patients progress through lines of therapy. Clinical trials in the relapsed/refractory multiple myeloma (RRMM) setting have not uniformly included patients with RI or robustly reported their outcomes. Here, we review existing data among patients with RI and RRMM across drug classes (including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and exportin-1 inhibitor) to provide an improved understanding of available treatment options for this important population. We highlight data from pivotal clinical trials, including data relating to renal response (as defined by the International Myeloma Working Group) and discuss real-world experiences in patients with RI, where applicable. Despite substantial advances in RRMM treatment, the presence of RI remains associated with reduced overall survival. Consistent inclusion of patients with RI, and uniform reporting of their outcomes, should be encouraged in future prospective trials of treatments for RRMM.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-04-02T11:49:20Z
      DOI: 10.1177/20406207221088458
      Issue No: Vol. 13 (2022)
       
  • Cardiovascular-specific mortality among multiple myeloma patients: a
           population-based study

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      Authors: Xuejiao Yin, Fengjuan Fan, Bo Zhang, Yu Hu, Chunyan Sun
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:Multiple myeloma (MM) survival has greatly improved in recent decades. MM is usually diagnosed at a median age of 66–70 years. MM patients do not necessarily die from primary cancer, so cardiovascular health may be a key factor threatening long-term survival. This study was designed to explore the cardiovascular disease mortality (CVM) trends in MM patients and compare them with those in the general population.Methods:In total, 88,328 MM patients from the Surveillance, Epidemiology, and End Results (SEER) database (1975–2016) were included. Standardized mortality ratios (SMRs) were used to assess CVM risk.Results:The CVM risk was significantly higher in MM patients than in the general population (SMR, 1.84 (95% CI, 1.78–1.89)). MM patients had the highest CVM SMR, at 2.62 (95% CI, 2.49–2.75), in the first year after diagnosis, and it decreased over the follow-up period. Over the study period, the incidence of CVM continued to decrease in MM patients diagnosed at age 65–74 (APC, −1.2% (95% CI, −1.9% to −0.4%)) and ⩾75 years (APC, −1.9% (95% CI, −2.6% to −1.2%)) but not younger. CVM was the second-most common cause of death in patients ⩾75 years. In only MM case analyses, male sex, Black race, older age at diagnosis, and earlier year of diagnosis were poor prognostic factors for heart-specific mortality.Conclusion:The CVM risk in MM patients was significantly higher than that in the general population. To improve survival, cardiovascular health should receive attention upon diagnosis.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-31T07:10:50Z
      DOI: 10.1177/20406207221086755
      Issue No: Vol. 13 (2022)
       
  • A multicenter phase II study on the efficacy and safety of hetrombopag in
           patients with severe aplastic anemia refractory to immunosuppressive
           therapy

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      Authors: Guangxin Peng, Guangsheng He, Hong Chang, Sujun Gao, Xinjian Liu, Tong Chen, Pei Li, Bing Han, Miao Miao, Zheng Ge, Xiaoyan Ge, Fei Li, Yingmei Li, Shunqing Wang, Yi Wang, Yaqi Shen, Tao Zhang, Jianjun Zou, Fengkui Zhang
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:In this single-arm phase II study (NCT03557099), we evaluated the efficacy and safety of hetrombopag, a small molecule thrombopoietin (TPO) receptor agonist, in patients with severe aplastic anemia (SAA) who were refractory to standard first-line immunosuppressive therapy (IST).Methods:SAA patients who were refractory to standard first-line IST were given hetrombopag orally at an initial dose of 7.5 mg once daily to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in ⩾1 lineage at week 18.Results:A total of 55 eligible patients were enrolled and received hetrombopag treatment. This study met its primary endpoint, with 23 [41.8%, 95% confidence interval (CI) = 28.7–55.9] patients achieving hematologic response in ⩾1 lineage at week 18 after initiation of hetrombopag treatment. Twenty-four (43.6%, 95% CI = 30.3–57.7) and 27 (49.1%, 95% CI = 35.4–62.9) of the 55 patients responded in ⩾1 lineage at weeks 24 and 52, respectively. Median time to initial hematologic response was 7.9 weeks (range = 2.0–32.1). The responses were durable, with a 12-month relapse-free survival rate of 82.2% (95% CI = 62.2–92.2). Adverse events occurred in 54 (98.2%) patients, and 28 (50.9%) patients had treatment-related adverse events. Seventeen (30.9%) patients had adverse events of grade ⩾3. Serious adverse events occurred in 15 (27.3%) patients and three deaths (5.5%) were reported.Conclusion:Hetrombopag showed encouraging efficacy with durable hematologic responses in patients with SAA who were refractory to IST. Hetrombopag was well tolerant and safe for long-term use.ClinicalTrials.gov identifier:NCT03557099
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-30T10:08:38Z
      DOI: 10.1177/20406207221085197
      Issue No: Vol. 13 (2022)
       
  • Changing paradigms of hemophilia care across larger specialized treatment
           centers in the European region

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      Authors: Jerzy Windyga, Ana Boban, Irena Zupan, Niamh O’Connell, Cedric Hermans
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Introduction:In early 2021, the European Collaborative Haemophilia Network (ECHN) conducted a survey to determine whether the paradigms of care across the European region have changed with the introduction of novel therapies for people with hemophilia.Methods:We conducted a survey in 19 ECHN centers from 17 countries in the European region. The aim was to track recent changes in the hemophilia treatment landscape, determine the impact of these changes on hemophilia treatment centers and comprehensive care centers in the region, and to look into the future of care as applied to people with hemophilia. The survey was structured to include three key areas: demographics and organization; current challenges and opportunities; and future directions.Discussion:Our survey provides a snapshot of the current approach to hemophilia treatment that highlights a move toward preventive, rather than reactive care, but that also raises a number of key concerns related to costs and accessibility (particularly as related to novel therapies), time limitations for clinical research, and ongoing issues regarding human resources (particularly in terms of new doctors entering the field) and availability of laboratory resources as the use of novel therapies (some with unique modes of action and unusual adverse events, some with specialized monitoring requirements) becomes commonplace.Conclusion:While our survey suggests that specialized care will continue to play a central role in the management of hemophilia, the standards and protocols, as well as the centers themselves, will have to continue to evolve if they are to continue to provide the highest level of care. To meet this requirement, there is a clear need for engaging, ongoing education programs for healthcare professionals working in the field of hemophilia that can be adjusted to the changing landscape of hemophilia therapy and monitoring.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-28T12:43:19Z
      DOI: 10.1177/20406207221088462
      Issue No: Vol. 13 (2022)
       
  • A retrospective real-world study of the current treatment pathways for
           myelofibrosis in the United Kingdom: the REALISM UK study

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      Authors: Adam J. Mead, Nauman M. Butt, Waseem Nagi, Alastair Whiteway, Suriya Kirkpatrick, Ciro Rinaldi, Catherine Roughley, Sam Ackroyd, Joanne Ewing, Pratap Neelakantan, Mamta Garg, David Tucker, John Murphy, Hitesh Patel, Rozinder Bains, Gavin Chiu, Joe Hickey, Claire Harrison, Tim C. P. Somervaille
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom.Methods:The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment.Discussion:Two hundred patients were included (63% [n = 126/200] with primary MF; 37% [n = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. ‘Watch and wait’ was the first management strategy for 53.5% (n = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0–350); patients with higher risk disease were prescribed active treatment sooner.Conclusion:These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients.Plain Language SummaryBackground: Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient’s daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently.Methods: We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK.Results: The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was ‘watch and wait’, which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner.Conclusion: The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-28T10:46:57Z
      DOI: 10.1177/20406207221084487
      Issue No: Vol. 13 (2022)
       
  • A retrospective comparison of salvage intensive chemotherapy versus
           venetoclax-combined regimen in patients with relapsed/refractory acute
           myeloid leukemia (AML)

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      Authors: Silvia Park, Daehun Kwag, Tong Yoon Kim, Jong Hyuk Lee, Joon yeop Lee, Gi June Min, Sung Soo Park, Seung-Ah Yahng, Young-Woo Jeon, Seung-Hwan Shin, Jae-Ho Yoon, Sung-Eun Lee, Byung Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Hee-Je Kim
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Evidence that a venetoclax (VEN)-combined regimen is effective in relapsed/refractory acute myeloid leukemia (R/R AML) is emerging. However, it is unknown how VEN-combined low intensity treatment compares to intensive chemotherapy (IC) in medically fit patients with R/R AML.Methods:We compared AML patients who received IC (n = 89) to those who received a VEN in combination with hypomethylating agents or low dose cytarabine (VEN combination) (n = 54) as their first- or second-line salvage after failing anthracycline-containing intensive chemotherapy.Results:The median age was 49 years, and significantly more patients in the VEN combination group were in their second salvage and had received prior stem cell transplantation (SCT). Overall response rates including CR, CRi, and MLFS were comparable (44.0% for IC vs. 59.3% for VEN combination, p = 0.081), but VEN combination group compared to IC group tended to show lower treatment related mortality. The rate of bridging to SCT was the same (68.5%), but the percentage of SCT at blast clearance was significantly higher in the VEN-combined group (62.3% vs. 86.5%, p = 0.010). After median follow-up periods of 22.5 (IC) and 11.3 months (VEN combination), the median overall survival was 8.9 (95% CI, 5.4-12.4) and 12.4 months (95% CI, 9.5-15.2) (p = 0.724), respectively.Conclusion:VEN combination provides a comparable anti-leukemic response and survival to salvage IC, and provide a bridge to SCT with better disease control in medically-fit patients with R/R AML.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-23T10:05:48Z
      DOI: 10.1177/20406207221081637
      Issue No: Vol. 13 (2022)
       
  • Loncastuximab tesirine in relapsed or refractory diffuse large B-cell
           lymphoma: a review of clinical data

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      Authors: Fateeha Furqan, Mehdi Hamadani
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Loncastuximab tesirine-lpyl (ADC Therapeutics) is an anti-CD19 antibody-drug conjugate which consists of anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Data from preclinical in vitro and animal studies demonstrated its selectivity and efficacy. The phase I LOTIS-1 study for relapsed, refractory B-cell non-Hodgkin lymphoma (NHL) demonstrated efficacy and a tolerable safety profile, with major adverse effects being neutropenia, thrombocytopenia, elevated liver enzymes, and fluid accumulation. Based on pharmacokinetics analysis in this study, a dose of 150 μg/kg every 3 weeks for cycles 1 and 2 followed by 75 μg/kg every 3 weeks until disease progression or intolerability was chosen for the phase II LOTIS-2 study. This study recruited relapsed, refractory diffuse large B-cell lymphoma and confirmed similar safety profile. Overall response rate was 48.6% (24.1% complete response), and overall survival was 9.9 months. Due to its safety and efficacy reported in the above trials, loncastuximab tesirine was recently approved by the US Food and Drug Administration for the treatment of relapsed, refractory diffuse large B-cell lymphoma. Several clinical trials are ongoing to assess its safety and efficacy in NHL in various clinical settings.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-22T11:30:23Z
      DOI: 10.1177/20406207221087511
      Issue No: Vol. 13 (2022)
       
  • Iron overload status in patients with non-transfusion-dependent
           thalassemia in China

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      Authors: Yumei Huang, Gaohui Yang, Man Wang, Xiaoyun Wei, Lingyuan Pan, Jiaodi Liu, Yu Lei, Peng, Liling Long, Yongrong Lai, Rongrong Liu
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Iron overload is one of the main factors that increase morbidity and mortality in patients with non-transfusion dependent thalassemia (NTDT).Aim:This study aimed at investigating the prevalence and severity of iron overload in Chinese NTDT patients.Methods:we analyzed serum ferritin (SF), liver iron concentration (LIC) and cardiac T2* in 178 Chinese NTDT in this cross-sectional study.Results:The median SF level was 996.00(27.15–19704.00) ng/ml and the median LIC value was 8.90(0.60–43.00) mg Fe/g dry weight (dw). The youngest patient with liver iron overload was 5 years old with 5.6 mg Fe/g dw in LIC. The median cardiac T2* was 33.06(7.46–75.08) ms. 6 patients had cardiac T2*⩽20ms. The patients with β thalassemia intermedia and HbE/β thalassemia showed a statistically significant lower Hb and higher values of SF and LIC than those of hemoglobin H disease patients. On multivariate logistic regression analysis, patients in ⩾ age 30-year old had a significant higher risk for iron overload (OR: 77.75, 95% CI: 8.76–690.49) in the age group. The detailed analysis of proportions of different LIC indicate in  > 30-year old group, 76.8% patients suffered from moderate and severe LIC.Conclusion:Our study provides a strong support for the novel findings that Chinese NTDT patients have a high prevalence of iron overload. The first assessment of MRI LIC should be performed as early as 5 years old. Then, NTDT patients  > 30 years old may suffer with a high burden of iron overload.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-19T04:30:11Z
      DOI: 10.1177/20406207221084639
      Issue No: Vol. 13 (2022)
       
  • Idiopathic multicentric Castleman disease treated with siltuximab for
           15 years: a case report

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      Authors: Evan Lang, Brenda Sande, Samantha Brodkin, Frits van Rhee
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Human herpes virus-8 (HHV8)-negative, idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder sustained by pro-inflammatory cytokines, including interleukin-6 (IL-6). According to the international evidence-based criteria developed by the Castleman Disease Collaborative Network (CDCN), siltuximab, which works by inhibiting IL-6, is the recommended choice for iMCD treatment. We report a case of a 63-year-old white male with iMCD who has been on maintenance therapy with siltuximab for 15 years – representing one of the longest treatment periods of any patient with iMCD treated with siltuximab. The patient initially presented with fatigue and night sweats, with progressive worsening of the symptoms. Whole-body positron emission tomography/computed tomography revealed hypermetabolic lymphadenopathy. The patient had histopathologically confirmed Castleman disease, plasma cell type, and was negative for HHV8 and human immunodeficiency virus. The patient had abnormally high C-reactive protein (CRP) levels, a surrogate measure for IL-6. The patient was treated with high-dose steroids but had recurring lymphadenopathy early on. He was enrolled in the phase I dose-finding clinical trial of siltuximab, during which he achieved marked clinical improvement and sustained inhibition of CRP. The patient was enrolled in the long-term safety study and continues to receive siltuximab at 11 mg/kg every 3 weeks. He is presently receiving commercial siltuximab and has remained asymptomatic, with no evidence of lymphadenopathy. The case study presented is consistent with the evidence that siltuximab is a safe and effective therapy for the long-term management of iMCD. In addition, this case highlights the importance of prompt diagnosis for patients with iMCD, as effective therapy is available for patients as described in the CDCN and National Comprehensive Cancer Network iMCD treatment guidelines.Plain Language SummaryThe case of a 63-year-old white male with idiopathic multicentric Castleman disease who was successfully treated with siltuximab for 15 yearsIdiopathic multicentric Castleman disease (iMCD) is a group of rare lymphoproliferative disorders with shared histopathological features that affect lymph nodes in multiple regions of the body. The signs and symptoms of iMCD can be varied, with the disease being mild in some patients while life-threatening in others. A timely diagnosis of iMCD can be challenging but is required for effective management. We report a case of a patient who was diagnosed with iMCD. The patient was given high-dose steroids but continued to show progressive disease. He was then started on siltuximab, a targeted antibody therapy against a specific cytokine (interleukin-6) involved in inflammation. The patient responded well to the treatment, has shown evidence of long-term disease control, and has not reported any serious adverse events related to long-term siltuximab use. He has received 11 mg/kg of siltuximab every 3 weeks for the past 15 years. This case emphasizes the value of using siltuximab therapy for long-term management of this rare disorder. In addition, it highlights the importance of prompt diagnosis for patients with iMCD, as effective therapy is available, as described in iMCD treatment guidelines.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-03-02T12:40:41Z
      DOI: 10.1177/20406207221082552
      Issue No: Vol. 13 (2022)
       
  • Mantle cell lymphoma management trends and novel agents: where are we
           going'

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      Authors: Jeffrey J. Pu, Malvi Savani, Nick Huang, Elliot M. Epner
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      The heterogeneity in disease pathology, the unpredictability in disease prognosis, and the variability in response to therapy make mantle cell lymphoma (MCL) a focus of novel therapeutic development. MCL is characterized by dysregulated expression of cyclin D1 through a chromosome t(11;14) translocation. MCL international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation status are currently utilized for prognostication. With advances in pharmacokinetic analysis and drug discovery, treatment strategy has evolved from chemotherapy to combination of targeted, epigenetic, and immune therapies. In this review, we discuss investigational and newly approved treatment approaches. In a short time, the US Food and Drug Administration (FDA) has approved five agents for the treatment of MCL: lenalidomide, an immunomodulatory agent; bortezomib, a proteasome inhibitor; and ibrutinib, acalabrutinib, and zanubrutinib, all Bruton kinase inhibitors. Epigenetic agents (e.g. cladribine and vorinostat), mammalian target of rapamycin (mTOR) inhibitors (e.g. temsirolimus and everolimus), and monoclonal antibodies and/or antibody-drug conjugates (e.g. obinutuzumab, polatuzumab, and ublituximab) are promising therapeutic agents currently under clinical trial investigation. Most recently, chimeric antigen receptor (CAR)-T cell therapy and bispecific T-cell engager (BiTE) therapy even open a new venue for MCL treatment. However, due to its intricate pathology nature and high relapse incidence, there are still unmet needs in developing optimal therapeutic strategies for both frontline and relapsed/refractory settings. The ultimate goal is to develop innovative personalized combination therapy approaches for the purpose of delivering precision medicine to cure this disease.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-02-26T09:34:59Z
      DOI: 10.1177/20406207221080743
      Issue No: Vol. 13 (2022)
       
  • Outpatient allogeneic hematopoietic stem-cell transplantation: a review

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      Authors: David Gómez-Almaguer, Andrés Gómez-De León, Perla R. Colunga-Pedraza, Olga G. Cantú-Rodríguez, César Homero Gutierrez-Aguirre, Guillermo Ruíz-Arguelles
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Hematopoietic stem-cell transplantation (HSCT) is usually performed in well-equipped units inside a hospital. The cost of this in-hospital transplant is usually very high; therefore, this procedure is more difficult to perform in low- and middle-income countries. Autologous outpatient HSCT is now a common procedure; however, outpatient allogeneic transplants are more complicated. Only a few centers in the world have incorporated outpatient HSCT. This transplant requires special adaptation, like a day hospital, careful selection of patients, oral medications, and the patient must live relatively close to the hospital. The results until now suggest that this outpatient transplant is factible and similar to inpatient HSCT. The objective was to review and describe the different methods and results following an outpatient allogeneic-HSCT strategy.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-02-26T09:33:09Z
      DOI: 10.1177/20406207221080739
      Issue No: Vol. 13 (2022)
       
  • Chimeric antigen receptor (CAR) T-cell treatment for mantle cell lymphoma
           (MCL)

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      Authors: Bushra Tbakhi, Patrick M. Reagan
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Mantle cell lymphoma (MCL) is a rare B-cell malignancy that remains challenging to treat with high rates of relapse. Frontline strategies range from intensive chemotherapy followed by consolidation with autologous stem cell transplant (ASCT), to less-intensive therapies including combination regimens. The treatment landscape for relapsed patients includes Bruton tyrosine kinase (BTK) inhibitors among other targeted treatments. Novel agents such as the selective BCL2 inhibitor venetoclax showed high response rates when used as monotherapy for refractory relapsed MCL. The rituximab, bendamustine, and cytarabine (R-BAC) regimen, while response rates were high, were not durable. Chimeric antigen receptor (CAR) T-cell products targeting CD19 have been efficacious in relapsed and refractory MCL patients. Brexucabtagene autoleucel (brexu-cel, formerly KTE-X19) was approved by US Food and Drug Administration (FDA) in July, 2020, for treatment of refractory and relapsed MCL. This article provides an overview for the available management strategies for relapsed MCL and examines the role of CAR T-cell in the current and future treatment of MCL.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-02-26T09:31:36Z
      DOI: 10.1177/20406207221080738
      Issue No: Vol. 13 (2022)
       
  • Improvement in pain-related quality of life in patients with hemophilia A
           treated with rFVIIIFc individualized prophylaxis: post hoc analysis from
           the A-LONG study

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      Authors: John Pasi, Cédric Hermans, Zalmai Hakimi, Jameel Nazir, Samuel Aballéa, Monia Ezzalfani, Francis Fatoye
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Pain, a common symptom of hemophilia, begins early in life primarily due to joint bleeding. Recurrent bleeding adversely affects patients’ pain-related physical functioning, which can negatively impact their quality of life (QoL).Objective:Post hoc analysis of data from the A-LONG study (NCT01181128), to assess change over time in pain-related QoL in patients with severe hemophilia A treated prophylactically with recombinant factor VIII Fc fusion protein (rFVIIIFc).Methods:Patients who completed Haem-A-QoL (17–65 years) and EQ-5D-3L (⩾12–65 years) questionnaires at baseline (BL) and end of study (EoS). Individual-level changes were assessed using three pain-related items of the Haem-A-QoL ‘Physical Health’ domain and the pain/discomfort item of EQ-5D-3L. Distributions of responses (EoS versus BL) were compared using McNemar’s test.Results:A significantly greater proportion of patients reported they did not experience painful swellings (n = 87; 66% versus 46%, p 
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-02-26T09:30:16Z
      DOI: 10.1177/20406207221079482
      Issue No: Vol. 13 (2022)
       
  • A thrombopoietin receptor agonist to rescue an unusual platelet
           transfusion-induced reaction in a p.V1316M-associated von Willebrand
           disease type 2B patient

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      Authors: Caterina Casari, Remi Favier, Paulette Legendre, Alexandre Kauskot, Frederic Adam, Veronique Picard, Peter T. Lenting, Cecile V. Denis, Valerie Proulle
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      This report describes the first case of splenic injury in a patient with p.V1316M-associated von Willebrand disease type 2B (VWD2B) with chronic thrombocytopenia, successfully treated with nonoperative management including von Willebrand factor (VWF) replacement therapy, and platelet transfusions relayed by a thrombopoietin receptor agonist (TPO-RA, Eltrombopag). Eltrombopag was initially introduced to rescue an unusual post-platelet-transfusion reaction exacerbating the thrombocytopenia. In-depth analysis of the dramatic platelet count drop and VWF measurements timeline ruled out an allo-immune reaction and supported an alternative hypothesis of a sudden platelet clearance as a consequence of stress-induced release of abnormal VWF. One year later, a second life-threatening bleeding episode required urgent surgery successfully managed with VWF replacement therapy and platelet transfusions. Eltrombopag was further introduced in the post-surgery period to allow bleeding-free and platelet-transfusion-free successful recovery. Treatment decisions are particularly challenging in patients with VWD2B, and this case highlights how such decisions can benefit from understanding the molecular origin of platelet count fluctuations observed in these patients. Here, we successfully used a new therapeutic approach combining VWF-replacement therapy and initial platelet-transfusion relayed by TPO-RA to optimize patient management.Plain language summaryA combination of von Willebrand factor replacement and thrombopoietin receptor agonist in thrombocytopenic patients with von Willebrand disease type 2B: a new therapy approach to optimize patient management'Therapeutic management of patients with von Willebrand disease type 2B are particularly challenging in case of severe thrombocytopenia.Treatment includes von Willebrands factor replacement therapy and iterative platelet transfusions.We describe the first case of splenic injury in a patient with p.V1316M-associated von Willebrand disease type 2B successfully treated with nonoperative management including von Willebrand factor replacement therapy and platelet transfusions relayed by a thrombopoietin receptor agonist.We showed that the unusual post-platelet-transfusion reaction associated with a dramatic platelet count drop was a consequence of stress-induced release of abnormal von Willebrand factor.The combination of von Willebrand factor replacement therapy and thrombopoietin receptor agonist may offer a new therapeutic approach to optimize patient management.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-02-16T09:55:33Z
      DOI: 10.1177/20406207221076812
      Issue No: Vol. 13 (2022)
       
  • Durable outcomes of double cord blood transplantation in adults with acute
           lymphoblastic leukemia: high-risk features for early and long-term
           mortality

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      Authors: Jae-Ho Yoon, Gi June Min, Sung-Soo Park, Silvia Park, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Chang-Ki Min, Seok-Goo Cho, Jong Wook Lee, Seok Lee
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Cord blood transplantation (CBT) has been reported as an acceptable option with comparable outcomes to conventional donors in adults with acute lymphoblastic leukemia (ALL). We aimed to analyze the long-term CBT outcomes and risk factors for early and long-term mortalities.Methods:Between 2006 and 2020, 112 patients (median age: 35 years; 62 Ph-negative ALL and 50 Ph-positive ALL) were treated with double CBT. Conditioning regimen consisted of total body irradiation (12 Gy) plus cytarabine (9.0 g/m2) plus fludarabine (150 mg/ m2), and graft-versus-host disease (GVHD) prophylaxis was attempted by administering tacrolimus plus mycophenolate mofetil.Results:The median time for neutrophil and platelet recovery was 25 days (range: 5–59 days) and 34 days (range: 7–185 days), respectively. The cumulative incidence of acute GVHD at 1 year was 43.8%, and the incidence of acute GVHD with grades III–IV was 8.9%. The overall cumulative incidence of chronic GVHD was 22.0%, and the incidence of moderate to severe chronic GVHD was 8.5%. After a median follow-up of 60.1 months (range: 5.7–181.3 months), the 5-year cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) were 15.9% and 28.5% (9.7% and 27.2% for CR1), respectively, and the 5-year overall survival (OS) was 57.9% (66.5% for CR1). In multivariate analysis of 88 patients receiving double CBT in CR1, delayed CR1 was related to high CIR, and age older than 40 years was associated with high NRM and early mortality. Unexpectedly, Ph-positive ALL with MRD had a higher NRM and early mortality than Ph-negative ALL and Ph-positive ALL without MRD subgroups, possibly due to delayed neutrophil and platelet recovery.Conclusion:Our data suggest that double CBT for adult ALL in CR1 has a greater benefit in younger patients and in patients with Ph-positive ALL without MRD or Ph-negative ALL.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-02-16T09:53:14Z
      DOI: 10.1177/20406207221076762
      Issue No: Vol. 13 (2022)
       
  • MYD88L265P and CD79B double mutations type (MCD type) of diffuse large
           B-cell lymphoma: mechanism, clinical characteristics, and targeted therapy
           

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      Authors: Rongrong Chen, De Zhou, Lulu Wang, Lixia Zhu, Xiujin Ye
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      MYD88/CD79B-mutated (MCD) genotype is a genetic subgroup of diffuse large B-cell lymphoma (DLBCL) with the co-occurrence of MYD88L265P and CD79B mutations. MCD genotype is characterized by poor prognosis and extranodal involvement especially in immune-privileged sites. MCD model is dominated by activated B-cell (ABC)-like subtype of DLBCLs. It is generally accepted that the pathogenesis of MCD DLBCL mainly includes chronic active B-cell receptor (BCR) signaling and oncogenic MYD88 mutations, which drives pathological nuclear factor kappa B (NF-κB) activation in MCD lymphoid malignancies. CD79B and MYD88L265P mutations are frequently and contemporaneously founded in B-cell malignancies. The collaboration of the two mutations may explain the unique biology of MCD. Meanwhile, standard immunochemotherapy combine with different targeted therapies worth further study to improve the prognosis of MCD, according to genetic, phenotypic, and clinical features of MCD type. In this review, we systematically described mechanism, clinical characteristics, and targeted therapy of MCD DLBCL.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-01-31T11:40:51Z
      DOI: 10.1177/20406207211072839
      Issue No: Vol. 13 (2022)
       
  • Primary central nervous system lymphoma in the United States,
           1975–2017

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      Authors: Chenglan Lv, Jing Wang, Min Zhou, Jing-Yan Xu, Bing Chen, Yuan Wan
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Background:Primary central nervous system lymphoma (PCNSL) has received more attention because of an inferior prognosis. Less is known about the incidence rate, histological type, and survival rate of PCNSL, especially in the 2010s.Methods:Data of PCNSL from the Surveillance, Epidemiology, and End Results (SEER) registry database (SEER 9 registries and SEER 18 registries) were used. Incidence was estimated by age, gender, race, site, and histological type. Trends were analyzed using joinpoint regression and described as annual percent change (APC) and average annual percent change (AAPC). Five-year overall survival estimates were compared using log-rank tests.Results:Most PCNSL occurred in the brain, followed by the spinal cord. The most frequent histological type of PCNSL was diffuse large B-cell lymphoma, followed by marginal zone lymphoma. Incidence rate increased from 0.1/100,000 to 0.5/100,000 with an AAPC of 5.3% from 1975 to 2017. Incidence rates varied greatly between the younger and older age population. The 5-year overall survival rates in SEER 9 registries and SEER 18 registries were 30.5% and 37.4%, respectively. Even though the 5-year overall survival rate significantly increased from 27.9% for the 1975–1979 time period to 44.8% for the 2010–2017 time period, survival benefit could not be expected for patients ⩾60 years. The 5-year survival rate for elderly patients was about 30% in the 2010s.Conclusion:With aging, the incidence of PCNSL in the elderly is increased. Over the past decade, no advances have been made in the treatment of elderly PCNSL. Prospective trials with PCNSL are warranted to improve the survival of elderly patients.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-01-24T07:05:36Z
      DOI: 10.1177/20406207211066166
      Issue No: Vol. 13 (2022)
       
  • Diagnosis and management of multiple myeloma during pregnancy: case
           report, review of the literature, and an update on current treatments

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      Authors: Hila Magen, Michal J. Simchen, Shira Erman, Abraham Avigdor
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      The simultaneous occurrence of pregnancy and multiple myeloma (MM) is rare. The challenge of diagnosing MM during pregnancy is demonstrated in the case presented here. Despite the rarity of concurrent MM and pregnancy, this possibility should be considered in patients with signs and symptoms that may be attributed to MM so as not to delay the diagnosis and decision about pregnancy continuation and initiation of an appropriate and safe therapy to the mother and fetus. Treating physicians should be aware of the potential effects of MM therapies on the fetus and pregnancy outcomes.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-01-21T12:09:03Z
      DOI: 10.1177/20406207211066173
      Issue No: Vol. 13 (2022)
       
  • Efficacy and safety of mesenchymal stem cells treatment for
           multidrug-resistant graft-versus-host disease after haploidentical
           allogeneic hematopoietic stem cell transplantation

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      Authors: Meng-Zhu Shen, Xin-Xin Liu, Zhi-Yuan Qiu, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Chen-Hua Yan, Huan Chen, Yu-Hong Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Si-Ning Liu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Dong Mo
      Abstract: Therapeutic Advances in Hematology, Volume 13, Issue , January-December 2022.
      Purpose:Graft-versus-host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT.Methods:MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0–2.0) × 106/kg once a week.Results:A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 106 cells/kg (range, 0.8–1.8 × 106) cells/kg, and the median numbers of infusion were 2 (range, 1–7) and 3 (range, 2–12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16–118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression (n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function (n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22–84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression (n = 2), severe fungal pneumonia (n = 1), and relapse (n = 1).Conclusion:MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.
      Citation: Therapeutic Advances in Hematology
      PubDate: 2022-01-20T10:15:35Z
      DOI: 10.1177/20406207211072838
      Issue No: Vol. 13 (2022)
       
 
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