Advances in Hematology
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Open Access journal
ISSN (Print) 1687-9104 - ISSN (Online) 1687-9112
Published by Hindawi [333 journals]
- The Evolution of Prognostic Factors in Multiple Myeloma
Abstract: Multiple myeloma (MM) is a heterogeneous hematologic malignancy involving the proliferation of plasma cells derived by different genetic events contributing to the development, progression, and prognosis of this disease. Despite improvement in treatment strategies of MM over the last decade, the disease remains incurable. All efforts are currently focused on understanding the prognostic markers of the disease hoping to incorporate the new therapeutic modalities to convert the disease into curable one. We present this comprehensive review to summarize the current standard prognostic markers used in MM along with novel techniques that are still in development and highlight their implications in current clinical practice.
PubDate: Tue, 21 Feb 2017 08:19:18 +000
- Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Trait among
Prospective Blood Donors: A Cross-Sectional Study in Berekum, Ghana
Abstract: Background. Blood transfusion is a therapeutic procedure usually undertaken in patients with severe anaemia. In Ghana, severe anaemia is mostly due to malaria caused by severe Plasmodium falciparum infection, road traffic accidents, and haemoglobinopathy-induced acute haemolysis. Method. This cross-sectional study evaluated coinheritance of sickle cell haemoglobin variant and G6PD enzymopathy among individuals that donated blood at the Holy Trinity Hospital, Berekum, in the Brong-Ahafo Region, Ghana. Demographic data and other pertinent information were captured using questionnaire. Sickle cell haemoglobin variants were determined using cellulose acetate electrophoresis (pH 8.6). Qualitative G6PD status and quantitative G6PD enzyme activity were determined using methaemoglobin reduction and Trinity Biotech G6PD test kit, respectively. Results. Prevalence of sickle cell trait (SCT) and G6PD enzymopathy coinheritance was 7%. In addition, 19.5% of the donors had 10%–60% of normal G6PD enzyme activity suggesting that these donor units are prone to stressor-induced acute haemolysis when given to recipients. Mild G6PD activity (, OR: 2.410 (CI: 1.049–5.534)), commercial (, OR: 5.609 (CI: 1.309–24.035)), and voluntary (, OR: 2.404 (CI: 1.071–5.397)) donors were significantly associated with SCT. Conclusion. Screening for red cell pathologies must be incorporated into existing protocols for populations with high incidence of haemoglobinopathies to protect high-risk recipients.
PubDate: Wed, 14 Sep 2016 12:07:57 +000
- Autologous Graft-versus-Tumor Effect: Reality or Fiction'
Abstract: In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients.
PubDate: Mon, 22 Aug 2016 17:04:17 +000
- Haploidentical Family Donor Transplantation: At the Crossroads of a
PubDate: Thu, 02 Jun 2016 06:15:01 +000
- Haploidentical Stem Cell Transplantation in Adult Haematological
Abstract: Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients.
PubDate: Mon, 30 May 2016 07:02:50 +000
- Clinical Scenarios for Discordant Anti-Xa
Abstract: Anti-Xa test measures the activity of heparin against the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed. Objective. To review the most common clinical settings in which anti-Xa results can be bias. Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013. Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombolysis and in patients with hyperbilirubinemia; limited published data evaluating the safety and effectiveness of anti-Xa assays for managing UH therapy is available. Conclusions and Relevance. To our knowledge this is the first paper that summarizes the most common causes in which this assay can be affected, several “day to day” clinical scenarios can modify the outcomes, and we concur that these rarely recognized scenarios can be affected by negative outcomes in the daily practice.
PubDate: Thu, 12 May 2016 14:57:29 +000
- Combined Bone Marrow and Kidney Transplantation for the Induction of
Abstract: The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable.
PubDate: Sat, 30 Apr 2016 13:21:11 +000
- HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide
Abstract: The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial.
PubDate: Thu, 07 Apr 2016 13:50:22 +000
- Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell
Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies
in Adults: Peripheral Blood or Bone Marrow—Review of Published
Abstract: Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting.
PubDate: Mon, 28 Mar 2016 11:07:23 +000
- Haploidentical Transplantation in Children with Acute Leukemia: The
Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) remains a curative option for children with high risk and advanced acute leukemia. Yet availability of matched family donor limits its use and although matched unrelated donor or mismatched umbilical cord blood (UCB) are viable options, they fail to meet the global need. Haploidentical family donor is almost universally available and is emerging as the alternate donor of choice in adult patients. However, the same is not true in the case of children. The studies of haploidentical HSCT in children are largely limited to T cell depleted grafts with not so encouraging results in advanced leukemia. At the same time, emerging data from UCBT are challenging the existing paradigm of less stringent HLA match requirements as perceived in the past. The use of posttransplantation cyclophosphamide (PTCY) has yielded encouraging results in adults, but data in children is sorely lacking. Our experience of using PTCY based haploidentical HSCT in children shows inadequacy of this approach in younger children compared to excellent outcome in older children. In this context, we discuss the current status of haploidentical HSCT in children with acute leukemia in a global perspective and dwell on its future prospects.
PubDate: Thu, 24 Mar 2016 09:23:01 +000
- Retracted: Plasmablastic Lymphoma: A Review of Current Knowledge and
PubDate: Thu, 24 Mar 2016 07:21:00 +000
- Review on Haploidentical Hematopoietic Cell Transplantation in Patients
with Hematologic Malignancies
Abstract: Allogenic hematopoietic cell transplantation (HSCT) is typically the preferred curative therapy for adult patients with acute myeloid leukemia, but its use has been reduced as a consequence of limited donor availability in the form of either matched-related donors (MRD) or matched-unrelated donors (MUD). Alternative options such as unrelated umbilical cord blood (UCB) transplantation and haploidentical HSCT have been increasingly studied in the past few decades to overcome these obstacles. A human leukocyte antigen- (HLA-) haploidentical donor is a recipient’s relative who shares an exact haplotype with the recipient but is mismatched for HLA genes on the unshared haplotype. These dissimilarities pose several challenges to the outcomes of the patient receiving such a type of HSCT, including higher rates of bidirectional alloreactivity and graft failure. In the past 5 years, however, several nonrandomized studies have shown promising results in terms of graft success and decreased rates of alloreactivity, in part due to newer grafting techniques and graft-versus-host disease (GVHD) prophylaxis. We present here a summary and review of the latest results of these studies as well as a brief discussion on the advantages and challenges of haploidentical HSCT.
PubDate: Mon, 29 Feb 2016 11:59:20 +000
- Biochemical Markers of Bone Turnover in Patients with β-Thalassemia
Major: A Single Center Study from Southern Pakistan
Abstract: Objectives. Skeletal complications in β-homozygous thalassemic patients are uncommon but often debilitating, even amongst children and adolescent patients with well maintained transfusion and chelation therapy. The aim is to evaluate the biochemical markers of bone turnover in regularly transfused thalassemic patients and its possible correlations with demographic data and hematological and biochemical markers. Methods. In this prospective cross-sectional study, 36 β-thalassemia major patients were enrolled from March 2012 to March 2014. All patients underwent complete blood counts, LFTs, serum ferritin, serum calcium, phosphorus, serum albumin, alkaline phosphatase, 25-OH vitamin D, and parathormone (PTH) levels. Results. There were 17 males and 19 females with mean age of 12.56 ± 5.9 years. Hypocalcemia and hypophosphatemia were seen in 66.6% and 19.4%, respectively, while 25-OH vitamin D deficiency was present in 72.2% of thalassemic children and adolescents. Hypoparathyroidism was seen in 13.8% while hyperparathyroidism was detected in 8.3% of patients. There was direct correlation between serum phosphorus and ferritin levels (). No correlation was found between indirect bilirubin and skeletal parameters, calcium and parathyroid hormone (). Conclusions. Biochemical profile is significantly altered in patients with β-thalassemia major and bone associated biochemical abnormalities like hypocalcaemia, 25-OH vitamin D deficiency, and hypophosphatemia are not uncommon in Pakistani patients with thalassemia major.
PubDate: Wed, 24 Feb 2016 11:10:49 +000
- Characterization of IXINITY® (Trenonacog Alfa), a Recombinant Factor IX
with Primary Sequence Corresponding to the Threonine-148 Polymorph
Abstract: The goal of these studies was to extensively characterize the first recombinant FIX therapeutic corresponding to the threonine-148 (Thr-148) polymorph, IXINITY (trenonacog alfa [coagulation factor IX (recombinant)]). Gel electrophoresis, circular dichroism, and gel filtration were used to determine purity and confirm structure. Chromatographic and mass spectrometry techniques were used to identify and quantify posttranslational modifications. Activity was assessed as the ability to activate factor X (FX) both with and without factor VIIIa (FVIIIa) and in a standard clotting assay. All results were consistent across multiple lots. Trenonacog alfa migrated as a single band on Coomassie-stained gels; activity assays were normal and showed 97%γ-carboxylation and underwent the appropriate structural change upon binding calcium ions. Trenonacog alfa was activated normally with factor XIa (FXIa); once activated it bound to FVIIIa and FXa. When activated to FIXa, it was inhibited efficiently by antithrombin. Glycosylation patterns were similar to plasma-derived FIX with sialic acid content consistent with the literature reports of good pharmacokinetic performance. These studies have shown that trenonacog alfa is a highly pure product with a primary sequence and posttranslational modifications consistent with the common Thr-148 polymorphism of plasma-derived FIX.
PubDate: Sun, 21 Feb 2016 11:35:47 +000
- Seroprevalence of Hepatitis C, Hepatitis B, Cytomegalovirus, and Human
Immunodeficiency Viruses in Multitransfused Thalassemic Children in Upper
Abstract: Background. Frequent blood transfusions in thalassemia major children expose them to the risk of transfusion-transmitted infections (TTIs). The aim of this study was to estimate the prevalence of hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and cytomegalovirus (CMV) in thalassemic children attending the Pediatrics Departments of both Sohag and Minia Universities of Upper Egypt, during the period from May 2014 to May 2015. Methods. Serum samples were screened for hepatitis B surface antigen (HBsAg), anti-HCV, anti-CMV, and anti-HIV type 1 and type 2 using the Vitek Immunodiagnostic Assay System. Results. The frequencies of anti-HCV, HBsAg, anti-CMV, and anti-HIV type 1 and type 2 were found to be 37.11%, 4.12%, 4.12%, 0.00%, and 0.00%, respectively. Seropositivity for anti-HCV, HBsAg, and anti-CMV increased with increasing age of the patients, duration of the disease, serum ferritin level (ng/mL), and liver enzymes (U/L), while it was not significantly associated with gender, frequency of blood transfusion, or the status of splenectomy operation (). Conclusion. The frequency of TTIs, especially HCV, is considerably high among Egyptian children with thalassemia major. It is therefore important to implement measures to improve blood transfusion screening, such as polymerase chain reaction, in order to reduce TTIs from blood donor units.
PubDate: Wed, 17 Feb 2016 14:07:46 +000
- Relative Susceptibilities of ABO Blood Groups to Plasmodium falciparum
Malaria in Ghana
Abstract: The clinical outcome of falciparum malaria in endemic areas is influenced by erythrocyte polymorphisms including the ABO blood groups. Studies have reported association of ABO blood group to resistance, susceptibility, and severity of P. falciparum malaria infection. Individuals with blood group “A” have been found to be highly susceptible to falciparum malaria whereas blood group “O” is said to confer protection against complicated cases. We analyzed samples from 293 young children less than six years old with malaria in the Korle-Bu Teaching Hospital in Accra, Ghana. It was observed that group O was present in about 16.1% of complicated cases weighed against 40.9% of uncomplicated controls. Individuals with complicated malaria were about twice likely to be of blood groups A and B compared to group O (A versus O, OR = 1.90, 95% CI = 1.59–2.26, ; B versus O, OR = 1.82. 95% CI = 1.57–2.23, ). Blood group O participants with complicated diseases had low parasitaemia compared to the other blood groups (). This may give blood group O individuals a survival advantage over the other groups in complicated malaria as suggested. Participants with complicated falciparum malaria were generally anaemic and younger than those with uncomplicated disease.
PubDate: Mon, 15 Feb 2016 08:38:49 +000
- Influence of Oxidative Stress on Stored Platelets
Abstract: Platelet storage and its availability for transfusion are limited to 5-6 days. Oxidative stress (OS) is one of the causes for reduced efficacy and shelf-life of platelets. The studies on platelet storage have focused on improving the storage conditions by altering platelet storage solutions, temperature, and materials. Nevertheless, the role of OS on platelet survival during storage is still unclear. Hence, this study was conducted to investigate the influence of storage on platelets. Platelets were stored for 12 days at 22°C. OS markers such as aggregation, superoxides, reactive oxygen species, glucose, pH, lipid peroxidation, protein oxidation, and antioxidant enzymes were assessed. OS increased during storage as indicated by increments in aggregation, superoxides, pH, conjugate dienes, and superoxide dismutase and decrements in glucose and catalase. Thus, platelets could endure OS till 6 days during storage, due to the antioxidant defense system. An evident increase in OS was observed from day 8 of storage, which can diminish the platelet efficacy. The present study provides an insight into the gradual changes occurring during platelet storage. This lays the foundation towards new possibilities of employing various antioxidants as additives in storage solutions.
PubDate: Tue, 02 Feb 2016 07:27:19 +000
- Haploidentical Hematopoietic Stem Cell Transplantation: Expanding the
Horizon for Hematologic Disorders
Abstract: Despite the advent of targeted therapies and novel agents, allogeneic hematopoietic stem cell transplantation remains the only curative modality in the management of hematologic disorders. The necessity to find an HLA-matched related donor is a major obstacle that compromises the widespread application and development of this field. Matched unrelated donors and umbilical cord blood have emerged as alternative sources of donor stem cells; however, the cost of maintaining donor registries and cord blood banks is very high and even impractical in developing countries. Almost every patient has an HLA haploidentical relative in the family, meaning that haploidentical donors are potential sources of stem cells, especially in situations where cord blood or matched unrelated donors are not easily available. Due to the high rates of graft failure and graft-versus-host disease, haploidentical transplant was not considered a feasible option up until the late 20th century, when strategies such as “megadose stem cell infusions” and posttransplantation immunosuppression with cyclophosphamide showed the ability to overcome the HLA disparity barrier and significantly improve the rates of engraftment and reduce the incidence and severity of graft-versus-host disease. Newer technologies of graft manipulation have also yielded the same effects in addition to preserving the antileukemic cells in the donor graft.
PubDate: Tue, 02 Feb 2016 07:22:40 +000
- Donor Specific Anti-HLA Antibody and Risk of Graft Failure in
Haploidentical Stem Cell Transplantation
Abstract: Outcomes of allogeneic hematopoietic stem cell transplantation (AHSCT) using HLA-half matched related donors (haploidentical) have recently improved due to better control of alloreactive reactions in both graft-versus-host and host-versus-graft directions. The recognition of the role of humoral rejection in the development of primary graft failure in this setting has broadened our understanding about causes of engraftment failure in these patients, helped us better select donors for patients in need of AHSCT, and developed rational therapeutic measures for HLA sensitized patients to prevent this unfortunate event, which is usually associated with a very high mortality rate. With these recent advances the rate of graft failure in haploidentical transplantation has decreased to less than 5%.
PubDate: Sun, 24 Jan 2016 14:12:51 +000
- Myeloablative Conditioning with PBSC Grafts for T Cell-Replete
Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide
Abstract: Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based () and a TBI-based MA preparative regimen (), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation.
PubDate: Thu, 21 Jan 2016 06:51:10 +000
- Comparison of Bone Mineral Density in Thalassemia Major Patients with
Abstract: Chronic hemoglobinopathies like thalassemia are associated with many osteopathies like osteoporosis. Methods. This observational study was carried out to compare the bone mineral density (BMD) in transfusion dependent thalassemics with that of healthy controls. Thirty-two thalassemia patients, aged 2–18 years, and 32 age and sex matched controls were studied. The bone mineral concentration (BMC) and BMD were assessed at lumbar spine, distal radius, and neck of femur. Biochemical parameters like serum calcium and vitamin D levels were also assessed. Results. The BMC of neck of femur was significantly low in cases in comparison to controls. We also observed significantly lower BMD at the lumbar spine in cases in comparison to controls. A significantly positive correlation was observed between serum calcium levels and BMD at neck of femur. Conclusion. Hence, low serum calcium may be used as a predictor of low BMD especially in populations where incidence of hypovitaminosis D is very high.
PubDate: Thu, 31 Dec 2015 06:51:56 +000
- Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive
Abstract: BCR-ABL-mediated leukemias, either Chronic Myeloid Leukemia (CML) or Philadelphia positive Acute Lymphoblastic Leukemia (ALL), are the paradigm of targeted molecular therapy of cancer due to the impressive clinical responses obtained with BCR-ABL specific tyrosine kinase inhibitors (TKIs). However, BCR-ABL TKIs do not allow completely eradicating both CML and ALL. Furthermore, ALL therapy is associated with much worse responses to TKIs than those observed in CML. The identification of additional pathways that mediate BCR-ABL leukemogenesis is indeed mandatory to achieve synthetic lethality together with TKI. Here, we review the role of BCR-ABL/protein kinase CK2 interaction in BCR-ABL leukemias, with potentially relevant implications for therapy.
PubDate: Wed, 30 Dec 2015 13:52:42 +000
- Comparable Outcomes for Hematologic Malignancies after HLA-Haploidentical
Transplantation with Posttransplantation Cyclophosphamide and HLA-Matched
Abstract: The implementation of high-dose posttransplantation cyclophosphamide (PTCy) has made HLA-haploidentical (haplo) blood or marrow transplantation (BMT) a cost effective and safe alternative donor transplantation technique, resulting in its increasing utilization over the last decade. We review the available retrospective comparisons of haplo BMT with PTCy and HLA-matched BMT in adults with hematologic malignancies. The examined studies demonstrate no difference between haplo BMT with PTCy and HLA-matched BMT with regard to acute graft-versus-host disease (aGVHD), nonrelapse mortality, and overall survival. Chronic GVHD occurred less frequently after haplo BMT with PTCy compared with HLA-matched BMT utilizing standard GVHD prophylaxis. In addition, patients with a high risk of relapse by the disease risk index had a suggestion of improved progression-free and overall survival after haplo BMT with PTCy when compared with a historical cohort of HLA-matched BMT in one analysis. Furthermore, in Hodgkin lymphoma relapse and progression-free survival were improved in the haplo BMT with PTCy compared with the HLA-matched BMT cohort. These findings support the use of this transplantation platform when HLA-matched related donors (MRDs) are unavailable and suggest that clinical scenarios exist in which haplo BMT may be preferred to HLA-matched BMT, which warrant further investigation.
PubDate: Wed, 02 Dec 2015 12:42:31 +000
- Real-World Assessment of Clinical Outcomes in Patients with Lower-Risk
Myelofibrosis Receiving Treatment with Ruxolitinib
Abstract: Few trial-based assessments of ruxolitinib in patients with lower-risk myelofibrosis (MF) have been conducted, and no studies have made such assessments in a real-world population. We assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment using a retrospective, observational review of anonymized US medical record data of patients diagnosed with IPSS low-risk () or intermediate-1-risk () MF. The majority of patients were male (low risk, 60%; intermediate-1 risk, 69%). Most patients (92% and 77%) were still receiving ruxolitinib at the medical record abstraction date (median observation/exposure time, 8 months). The proportion of patients with moderate or severe palpable splenomegaly (≥10 cm) decreased from diagnosis (56%) to best response (12%). Fatigue was reported in 47% of patients and was the most common constitutional symptom. For most symptoms in both risk groups, shifts in the distribution of severity from more to less severe from diagnosis to best response were observed. Both patients with low-risk and intermediate-1-risk MF experienced a substantial decrease in spleen size with ruxolitinib treatment in real-world settings. For most symptoms examined, there were distinct improvements in the distribution of severity during ruxolitinib treatment. These findings suggest that patients with lower-risk MF may benefit clinically from ruxolitinib treatment.
PubDate: Mon, 09 Nov 2015 09:23:34 +000
- Decitabine Compared with Low-Dose Cytarabine for the Treatment of Older
Patients with Newly Diagnosed Acute Myeloid Leukemia: A Pilot Study of
Safety, Efficacy, and Cost-Effectiveness
Abstract: Introduction. The incidence of Acute Myeloid Leukemia (AML) increases progressively with age and its treatment is challenging. This prospective case control study was undertaken to compare the safety, efficacy, and cost-effectiveness of decitabine with those of cytarabine in older patients with newly diagnosed AML who are not fit for intensive chemotherapy. Materials and Methods. 30 eligible patients above 60 years old with newly diagnosed AML were assigned to receive decitabine or cytarabine. The primary end point was overall survival (OS). The secondary objective was to compare adverse events and cost-effectiveness of therapy in the two study groups. Results. In this study, 15 patients received decitabine and 15 patients received cytarabine. The median OS was 5.5 months for each of the treatment groups. The hazard ratio between the treatment groups was 0.811 with 95% CI of 0.390 to 1.687. Toxicity profile was similar in both groups. Cost per cycle of chemotherapy in INR was 24,200 for decitabine and 1,600 for low-dose cytarabine group. Median of simplified cost-effectiveness ratio was 0.00022 for decitabine group and 0.0034 for low-dose cytarabine group. Conclusions. For elderly patients with AML, decitabine and low-dose cytarabine should be chosen based on the patient’s choice and affordability. Our study has shown that both of these agents have similar OS and toxicity. Low-dose cytarabine scores over decitabine in developing countries as it is more cost-effective.
PubDate: Wed, 04 Nov 2015 06:00:25 +000
- Profiling β Thalassemia Mutations in Consanguinity and Nonconsanguinity
for Prenatal Screening and Awareness Programme
Abstract: Mutation spectrum varies significantly in different parts and different ethnic groups of India. Social factors such as preference to marry within the community and among 1st degree relatives (consanguinity) play an important role in impeding the gene pool of the disease within the community and so in society by and large. The present paper discusses the role of consanguinity in profiling of beta thalassemia mutation, and thus the approach for prenatal screening and prevention based awareness programme. Clinically diagnosed 516 cases of beta thalassemia were screened at molecular level. A detailed clinical Proforma was recorded with the information of origin of the family, ethnicity, and consanguinity. The present study reports that subjects originating from Uttar Pradesh, Uttarakhand, Bihar, and Jharkhand have c.92+5G>C and c.124_127delTTCT mutation as the commonest mutation compared to the subjects hailing from Madhya Pradesh and Chhattisgarh and Nepal where sickle mutation was found more common. In 40 consanguineous unions more common and specific beta mutations with higher rate of homozygosity have been reported. This consanguinity-based data helps not only in deciding target oriented prenatal diagnostic strategies but also in objective based awareness programmes in prevention of thalassemia major birth.
PubDate: Wed, 21 Oct 2015 07:15:33 +000
- The Iron Status of Sickle Cell Anaemia Patients in Ilorin, North Central
Abstract: Objectives. Sickle cell anaemia (SCA) is one of the commonest genetic disorders in the world. It is characterized by anaemia, periodic attacks of thrombotic pain, and chronic systemic organ damage. Recent studies have suggested that individuals with SCA especially from developing countries are more likely to be iron deficient rather than have iron overload. The study aims to determine the iron status of SCA patients in Ilorin, Nigeria. Methods. A cross-sectional study of 45 SCA patients in steady state and 45 non-SCA controls was undertaken. FBC, blood film, sFC, sTfR, and sTfR/log sFC index were done on all subjects. Results. The mean patients’ serum ferritin (589.33 ± 427.61 ng/mL) was significantly higher than the mean serum ferritin of the controls (184.53 ± 119.74 ng/mL). The mean serum transferrin receptor of the patients (4.24 ± 0.17 μg/mL) was higher than that of the controls (3.96 ± 0.17 μg/mL) (). The mean serum transferrin receptor (sTfR)/log serum ferritin index of the patients (1.65 ± 0.27 μg/mL) was significantly lower than that of the control (1.82 ± 0.18 μg/mL) (). Conclusion. Iron deficiency is uncommon in SCA patients and periodic monitoring of the haematological, biochemical, and clinical features for iron status in SCA patients is advised.
PubDate: Thu, 15 Oct 2015 08:15:12 +000
- Erythrocyte Catalase Activity in More Frequent Microcytic Hypochromic
Anemia: Beta-Thalassemia Trait and Iron Deficiency Anemia
Abstract: Most common microcytic hypochromic anemias are iron deficiency anemia (IDA) and β-thalassemia trait (BTT), in which oxidative stress (OxS) has an essential role. Catalase causes detoxification of H2O2 in cells, and it is an indispensable antioxidant enzyme. The study was designed to measure erythrocyte catalase activity (ECAT) in patients with IDA (10) or BTT (21), to relate it with thalassemia mutation type (β0 or β+) and to compare it with normal subjects (67). Ninety-eight individuals were analyzed since September 2013 to June 2014 in Tucumán, Argentina. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA2, catalase, and iron status were performed. β-thalassemic mutations were determined by real-time PCR. Normal range for ECAT was 70,0–130,0 MU/L. ECAT was increased in 14% (3/21) of BTT subjects and decreased in 40% (4/10) of those with IDA. No significant difference () was shown between normal and BTT groups, while between IDA and normal groups the difference was proved to be significant (). In β0 and β+ groups, no significant difference () was observed. An altered ECAT was detected in IDA and BTT. These results will help to clarify how the catalase activity works in these anemia types.
PubDate: Wed, 07 Oct 2015 14:22:23 +000
- Determinants of Overall and Progression-Free Survival of Nigerian Patients
with Philadelphia-Positive Chronic Myeloid Leukemia
Abstract: Objective. The tyrosine kinase inhibitors have markedly changed the disease course for patients with Ph+ and/or BCR-ABL1+ chronic myeloid leukemia (CML). This study was embarked upon to assess the long-term effects of imatinib therapy on survival in adult Nigerian patients with CML. Methods. All adult patients on imatinib (400–600 mg) seen from July 2003 to December 2010 were assessed. Male/female distribution was 171/101, with a median age of 38 (range, 20–75) years. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan-Meier techniques. Results. Of all the 272 patients, 205 were in chronic phase, 54 in accelerated phase, and five in blastic phase, at commencement of imatinib. As at December 2010, 222 were alive. OS at 1 and 5 years was 94% and 63%, while PFS was 89% and 54%, respectively. Similarly, amongst the 205 patients in chronic phase, OS at 1 and 5 years was 97% and 68%, while PFS was 92% and 57%. Conclusion. Imatinib’s place as first-line therapy in the treatment of CML has further been reinforced in our patients, with improved survival and reduced morbidity, comparable with outcomes in other populations.
PubDate: Mon, 07 Sep 2015 09:51:58 +000
- Frequency of Red Cell Alloimmunization and Autoimmunization in Thalassemia
Patients: A Report from Eastern India
Abstract: Introduction. Red blood cell (RBC) alloimmunization and autoimmunization remain a major problem in transfusion dependent thalassemic patients. There is a paucity of data on the incidence of RBC alloimmunization and autoimmunization in thalassemic patients from eastern part of India, as pretransfusion antibody screening is not routinely performed. Aims. To assess the incidence of RBC alloimmunization and autoimmunization in transfusion dependent thalassemic patients in eastern India. Materials and Methods. Total 500 thalassemia cases were evaluated. The antibody screening and identification were performed with commercially available panel cells (Diapanel, Bio-rad, Switzerland) by column agglutination method. To detect autoantibodies, autocontrol and direct antiglobulin tests were carried out using polyspecific coombs (IgG + C3d) gel cards in all patients. Results. A total of 28 patients developed RBC alloimmunization (5.6%) and 5 patients had autoantibodies (1%). Alloantibody against c had the highest incidence (28.57%) followed by E (21.42%). Five out of 28 (17.85%) patients had developed antibodies against both c and E. Conclusion. Data from this study demonstrate that the RBC alloantibody and autoantibody development rates are significant in our region. Thus, pretransfusion antibody screening needs to be initiated in eastern India in order to ensure safe transfusion practice.
PubDate: Sun, 06 Sep 2015 11:11:56 +000