Abstract: Objectives. The aim of this study was to compare the creatinine equations with cystatin C (CysC) equations to define renal impairment (RI) in newly diagnosed multiple myeloma (MM) patients and to analyse the equation that allows for identifying patients with more and worse prognostic factors. Methods. Renal function was evaluated prospectively in 61 patients with newly diagnosed untreated MM employing CKD-EPI and CAPA equations. The comparison was conducted using Bland–Altman graphics and Cohen’s Kappa statistic. Mann–Whitney T and Chi-square tests were used, and univariate and multivariate analyses were carried out. Results. According to the IMWG criteria, 26% of patients showed RI (3 women/13 men) whilst the use of CysC equations allowed us to identify up to 39% of patients (7 women/17 men). The CAPA equation was less biased and dispersed and more sensitive than CKD-EPI-creatinine. Furthermore, univariate analysis unveiled an association between decreased CKD-EPI-CysC and poor prognosis based on R-ISS-3. Conclusions. The IMWG criteria may underestimate kidney disease, mostly in women, which could affect the dose received as well as its toxicity. Altogether, our data suggest that equations that include CysC are more accurate to detect hidden kidney disease, as well as patients with more and worse prognostic factors, in newly diagnosed MM. PubDate: Sat, 16 Apr 2022 06:35:00 +000
Abstract: Objective. Mutational analysis by next-generation sequencing (NGS) obtained by peripheral blood NGS has been of clinical interest to use as a minimally invasive screening tool. Our study evaluates the correlation between NGS results on peripheral blood and bone marrow in hematolymphoid disease. Method. We evaluated patients who had NGS for presumed hematologic malignancy performed on peripheral blood and bone marrow within a 1-year interval of each other. We excluded cases in which chemotherapy or bone marrow transplant occurred in the interval between the two tests. The concordance across peripheral blood and bone marrow NGS results was assessed by kappa coefficient analysis. Results. A total of 163 patients were studied. Concordance of peripheral blood and bone marrow NGS found in 150 patients (92.0%) with a kappa coefficient of 0.794 (kappa standard error 0.054) and value for testing kappa PubDate: Sat, 26 Mar 2022 04:35:00 +000
Abstract: Background. Bone marrow infiltration of lymphoma cells is a candidate risk factor for infusion-related reactions (IRRs) in patients with CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). However, despite with the lack of sufficient data, the effect of bone marrow infiltration of B-NHL cells on the incidence rate of grade 2 or higher IRRs with the administration of rituximab has been retrospectively studied in this paper. Methods. Patients with CD20-positive B-NHL who received the rituximab induction therapy for the first time were enrolled in this study. To evaluate the bone marrow infiltration of B-NHL cells, May–Giemsa stain of bone marrow films and flow cytometry examination of bone marrow aspiration samples were performed. IRR grade was determined using the IRR criteria in the Common Terminology Criteria for Adverse Events version 4.0. Results. A total of 127 patients were eligible for this study. Grade 2 or higher IRRs were observed in 43 (34%) patients. In univariate analysis, use of glucocorticoid before rituximab infusion was a strong risk-avoiding factor for grade 2 or higher IRRs. Advanced stage of disease (Ann Arbor: stages III and IV) or bone marrow infiltration of B-NHL cells revealed the risk factors, regardless of glucocorticoid premedication. Using multivariate analysis, bone marrow infiltration was found to be an independent risk factor for patients without prior glucocorticoid use. Conclusion. Bone marrow infiltration of B-NHL cells is a risk factor for grade 2 or higher IRRs at the first rituximab induction therapy without glucocorticoid premedication. PubDate: Fri, 11 Feb 2022 04:35:00 +000
Abstract: Subcutaneous (SC) rituximab may be beneficial in terms of convenience and tolerability, with potentially fewer and less severe administration-related reactions (ARRs) compared to the intravenous (IV) form. This report presents the results of a phase IIIb study conducted in Italy. The study included adult patients with CD20+ DLBCL or FL having received at least one full dose of IV RTX 375 mg/m2 during induction or maintenance. Patients on induction received ≥4 cycles of RTX SC 1400 mg plus standard chemotherapy and FL patients on maintenance received ≥6 cycles of RTX SC. Overall, 159 patients (73 DLBCL, 86 FL) were enrolled: 103 (54 DLBCL, 49 FL) completed induction and 42 patients with FL completed 12 maintenance cycles. ARRs were reported in 10 patients (6.3%), 3 (4.2%) with DLBCL and 7 (8.1%) with FL, all of mild severity, and resolved without dose delay/discontinuation. Treatment-emergent adverse events (TEAEs) and serious adverse events occurred in 41 (25.9%) and 14 patients (8.9%), respectively. Two patients with DLBCL had fatal events: Klebsiella infection (related to rituximab) and septic shock (related to chemotherapy). Neutropenia (14 patients, 8.9%) was the most common treatment-related TEAE. Two patients with DLBCL (2.8%) and 6 with FL (7.0%) discontinued rituximab due to TEAEs. 65.2% and 69.7% of patients with DLBCL and 67.9% and 73.6% of patients with FL had complete response (CR) and CR unconfirmed, respectively. The median time to events (EFS, PFS, and OS) was not estimable due to the low rate of events. At a median follow-up of 29.5 and 47.8 months in patients with DLBCL and FL, respectively, EFS, PFS, and OS were 70.8%, 70.8%, and 80.6% in patients with DLBCL and 77.9%, 77.9%, and 95.3% in patients with FL, respectively. The switch from IV to SC rituximab in patients with DLBCL and FL was associated with low risk of ARRs and satisfactory response in both groups. This trial was registered with NCT01987505. PubDate: Thu, 27 Jan 2022 05:35:01 +000
Abstract: Background. The stress of academic life may predispose young adults to poor dietary habits, which could potentially precipitate nutritional deficiencies, such as iron deficiency. This study evaluated factors predictive of optimal iron stores as well as changes in haematological parameters over the course of an academic year in a cohort of tertiary students. Materials and Methods. The repeated-measure cohort study recruited 117 undergraduate students from September 2018 to May 2019. Venous blood samples were drawn for full blood count estimation, qualitative glucose-6-phosphate dehydrogenase (G6PD) status, haemoglobin variants, and blood group determination during the first 2 weeks of semester 1. However, anthropometric parameters as well as full blood counts were determined for each participant during the first week and last week of semesters 1 and 2. Additionally, semistructured questionnaires were used to capture sociodemographic data. Also, serum ferritin was estimated for each participant using enzyme-linked immunosorbent assay. Results. Overall, 23.1% and 15.5% of participants inherited G6PD defect (G6PDd) or haemoglobin variants, respectively. However, group O (68/117; 58.1%) was the predominant ABO blood group and an overwhelming 90.6% (106/117) inherited Rh D antigen. The prevalence of anaemia increased from 20% at the beginning of the first semester to 45.1% at the latter part of the second semester. G6PDd participants had significantly higher median serum ferritin than G6PD normal participants ( = 0.003). Also, a significantly higher proportion of females were iron depleted (25% vs. 2.3%) or iron deficient (14.3% vs. 9.3%) compared to males. Moreover, being male, G6PD deficient, or 21–25 years was associated with increased odds of participants having optimal serum ferritin levels. Conclusion. The progression of anaemia prevalence from mild to severe public health problem over the course of one academic year should urgently be addressed. PubDate: Sat, 22 Jan 2022 05:35:01 +000
Abstract: Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768). PubDate: Sat, 22 Jan 2022 05:35:01 +000
Abstract: Of the variety of immunoglobulin related amyloidosis (AL), immunoglobulin M (IgM) related AL represents only 6 to 10% of affected patients, and the majority of these cases are associated with underlying non-Hodgkin’s Lymphoma including Waldenström’s macroglobulinemia (WM). Ibrutinib, acalabrutinib, and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors approved for certain indolent B cell non-Hodgkin’s lymphoma (NHL). BTK is a nonreceptor kinase involved in B-cell survival, proliferation, and interaction with the microenvironment. We retrospectively evaluated the tolerability and effectiveness of BTK inhibitors ibrutinib and acalabrutinib therapy in (n = 4) patients with IgM-related AL amyloidosis with underlying WM. Treatment was well tolerated with both hematologic and organ response in patients with AL amyloidosis in the setting of WM. Atrial fibrillation led to the discontinuation of ibrutinib in one patient, and acalabrutinib caused significant thumb hematoma needing dose reduction in another patient. All patients evaluated had the MYD88 mutation. This may explain the good response to BTK inhibitors therapy in our series. BTK inhibitors should be further investigated in larger prospective studies for treatment of AL amyloidosis in patients with lymphoplasmacytic lymphoma/WM. PubDate: Wed, 19 Jan 2022 05:20:00 +000
Abstract: Introduction. Warfarin is a widely used oral anticoagulant in clinical practice. It has variable intraindividual and interindividual dose response and a narrow therapeutic index. Therefore, it requires frequent and regular international normalized ratio (INR) determination to maintain the INR within the therapeutic range. The study evaluated parameters of anticoagulation control among patients on warfarin. Methods. A cross-sectional study was conducted at University of Gondar hospital. A consecutive sampling method was used to recruit study subjects. The anticoagulation control was evaluated by determining the proportion of desired INRs and the proportion of time spent in the therapeutic range (TTR). Logistic regression analysis was used to identify associated factors with adequate TTR. A value PubDate: Tue, 21 Dec 2021 10:20:01 +000
Abstract: Background. Venous thromboembolism (VTE) is referred to as formation of clots in a deep vein or lodging of thrombus towards the lungs which could be fatal yet preventable. The risk of developing VTE can be increased by various factors. Where there are innumerable acquired causes, the possibility of inherited thrombophilia cannot be ignored. In view of this, we have evaluated all patients with venous thromboembolism for inherited thrombophilia. Objective. To evaluate the frequencies of antithrombin (AT) deficiency, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations in patients harboring venous thromboembolism. Materials and Methods. A study comprising of 880 patients who were presented with manifestations of venous thromboembolism was conducted from July 2016 to June 2017. A blood sample collected from patients was screened for thrombophilia defects encompassing AT, protein C and S deficiencies, Factor V Leiden, and prothrombin gene mutations. All acquired causes of thrombosis were excluded. Results. Of 880 patients who underwent screening for thrombophilia, 182 patients demonstrated VTE history. Their age ranged from 1 to 58 years. Males constituted a predominant group. About 45 (24.7%) patients had evidence of heritable thrombophilia. Of these, 20 (10.9%) had AT deficiency, 9 (4.9%) had Factor V Leiden mutation, 6 (3.2%) had protein C deficiency, whereas protein S deficiency and prothrombin gene mutation both were found in 5 (2.7%) patients. Conclusion. Our study illustrated the highest frequency of antithrombin deficiency among other investigated thrombophilia defects. PubDate: Mon, 25 Oct 2021 11:05:00 +000
Abstract: Haptoglobin is a protein involved in protecting the body from the harmful effects of free hemoglobin. The haptoglobin gene exhibits a polymorphism, and the different genotypes do not have the same capacity to combat the free hemoglobin effects. The present study aimed at determining the polymorphic distribution of haptoglobin in sickle cell patients (SCPs) from West Cameroon and their impact on the hematological parameters, as well as clinical manifestations of the disease severity. Haptoglobin genotype of 102 SCPs (SS) and 115 healthy individuals (60 AA and 55 AS) was determined by allele-specific polymerase chain reaction, and the complete blood count was determined using the AutoAnalyser. Results showed that the genotype Hp2-2 was significantly ( PubDate: Wed, 20 Oct 2021 09:05:00 +000
Abstract: The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation. PubDate: Wed, 21 Jul 2021 06:50:00 +000
Abstract: T-replete haploidentical donor transplants using posttransplant cyclophosphamide (haplo) have greatly expanded donor availability and are increasingly utilized. Haplo were originally performed using truly nonmyeloablative conditioning and a bone marrow graft. We have also developed myeloablative conditioning and peripheral blood stem cell (PBSC) grafts for use with haplo. However, some patients may not tolerate myeloablative conditioning but may still benefit from a more dose-intensified preparative regimen to control malignancy and diminish graft rejection. To this end, we enrolled 25 patients on a prospective phase II trial utilizing a regimen of fludarabine 30 mg/m2/day × 5 days and Melphalan 140 mg/m2 on day -1 (flu/Mel) followed by infusion of unmanipulated PBSC graft from a haploidentical donor. GVHD prophylaxis included cyclophosphamide 50 mg/kg/day on days 3 and 4, mycophenolate mofetil on day 35, and tacrolimus on day 180. Median age was 57 years (range from 35 to 68). Transplantation diagnosis included AML (n = 11), ALL (n = 4), MDS/MPD (n = 6), NHL/CLL (n = 3), and MM (n = 1). Using the refined Disease Risk Index (DRI), patients were low (n = 1), intermediate (n = 13), and high/very high (n = 11). 22 out of 25 patients engrafted with a median time to neutrophil and platelet engraftment of 18 days and 36 days, respectively. All engrafting patients achieved full peripheral blood T-lymphocyte and myeloid donor chimerism at day 30. The 180-day cumulative incidence for acute GVHD grades II–IV and III-IV was seen in 20% (95% CI 8%–37%) and 8% (95% CI 2%–22%), respectively. The 2-year cumulative incidence of chronic GVHD was 16% (95% CI 5%–33%) (moderate-severe 12% (95% CI 3%–27%)). After a median follow-up of 28.3 months, the estimated 2-year OS, DFS, NRM, and relapse were 56% (95%CI 33–74%), 44% (95%CI 23%–64%), 20% (95% CI 8%–37%), and 36% (95% CI 17%–55%), respectively. Among patients with high/very high risk DRI, 2-year OS was 53% compared to 69% for low/intermediate DRI. When compared with a contemporaneous cohort of patients at our center receiving haploidentical transplant with nonablative fludarabine, Cytoxan, and total body irradiation flu/Cy/TBI regimen, the outcomes were statistically similar to the 2-year OS at 56% vs. 63% and DFS at 44% vs. 46% . PubDate: Tue, 23 Mar 2021 11:20:00 +000
Abstract: Sickle cell disease is a hereditary disease that predominantly affects black people. It is very widespread in sub-Saharan Africa, particularly at the Lehmann “sickle belt” level, where the prevalence of the hemoglobin S involves at least 10% of the population in West Africa and can reach 40% in Central Africa. In Côte d’Ivoire, the prevalence of the hemoglobin S is about 12–14% in the general population and about 11.71% in the child population in Abidjan. On the other hand, its coexistence with other hemoglobin phenotypes such as AC (6.2%) and β-thalassemia (2.7%) traits may also cause composite heterogeneous sickle cell disease, e.g., SC or S/β-thalassemia in this study. Since 2009, sickle cell disease has been recognized as a public health problem; however, much still remains to be performed despite the progress achieved. The objective of this study is thus to promote a rapid screening for the struggling against sickle cell disease in Côte d’Ivoire. This study was carried out over 6 months (April–September 2019) and has included 336 children, of which 236 all-comers, recruited in the municipality of Treichville in Abidjan and 100 other children with already known hemoglobin phenotype followed up in the Hematology Department of the University Hospital of Treichville. Two tests were used: the HemoTypeSC™ for rapid screening and the hemoglobin electrophoresis which is the reference method used for confirming the diagnosis in the laboratory. The findings confirmed the reliability of the HemoTypeSC™ with a sensitivity and specificity at 100% for the detection of hemoglobin A, S, and C. On the other hand, this sensitivity and specificity drop to 98.2% and 99.7%, respectively, when we analyze all the 336 children together, including the cases with HbF detected by hemoglobin electrophoresis. Hence, the importance of performing certainty tests following the HemoTypeSC™ screening test in order to determine the accurate phenotypes and proportions of the types of hemoglobin. The prevalence of hemoglobin S in subgroup 1 of 236 children of all-comers was 15%. The HemoTypeSC™ is therefore reliable, inexpensive, and disposable for rapid screening and early detection of sickle cell disease in Côte d’Ivoire. The HemoTypeSC™ provides rapid detection of hemoglobin phenotypes HbAA, HbSS, HbSC, HbCC, HbAS, and HbAC. PubDate: Fri, 19 Mar 2021 11:05:00 +000
Abstract: Errors in transfusion of blood and blood products can lead to preventable morbidity and mortality. Nurses constitute a significant aspect of the transfusion process as they are the last in the chain of getting blood directly to the patient. They must, therefore, be conversant with the current standard of national and international guidelines on blood transfusion and appropriate management of adverse transfusion events. This study assesses the knowledge and practices of blood transfusion safety among nurses at Komfo Anokye Teaching Hospital. A descriptive cross-sectional design was employed, and structured questionnaire (Routine Blood Transfusion Knowledge Questionnaire) was used to collect data from 279 nurses from seven clinical directorates of the hospital. The data were processed with Stata version 14.0. Variables were analyzed using descriptive statistics, and relationships were drawn using inferential statistics. Over 90% of the respondents had a minimum of a diploma in nursing or midwifery, 63% had performed blood transfusion at least 5 times, and 46% had never received any training on blood transfusion. The mean score obtained in all four categories of blood transfusion knowledge assessed was 29, with 54% of the respondents scoring below the mean. The highest overall score on knowledge was 53%. This indicates that nurses had poor knowledge regarding safe blood transfusion practices as stipulated in the clinical guidelines for blood transfusion by Ghana’s National Blood Service. There was no statistically significant relationship between training/experience and knowledge of safe blood transfusion practices. Regular and continuous update training and audit are needed to safeguard patient safety during blood transfusion. PubDate: Tue, 02 Mar 2021 14:05:00 +000
Abstract: Background. Vaso-occlusive crisis (VOC) is the primary cause of hospitalization in patients with sickle cell disease. Treatment mainly consists of intravenous morphine or nonsteroidal anti-inflammatory drugs (NSAIDs), which have many dose-related side effects. The question arises as to whether vascular electrical stimulation therapy (VEST) could be effective or not on VOCs. Objective. To measure the effectiveness and safety of VEST in reducing the median time spent in severe VOC. Methods. We conducted a phase II, single blinded, randomized, controlled, triple-arm, comparative trial. We included thirty (30) adult patients with severe vaso-occlusive crisis. The study arms were divided as follows: our control group (group 0) constituted of 10 patients followed with conventional therapy (Analgesics + Hydration + NSAIDs), while 20 patients were divided equally into two interventional arms—10 patients followed with VEST + Analgesics + Hydration (group 1) and the other 10 patients followed with VEST + Analgesics + Hydration + NSAIDs (group 2). The primary efficacy endpoint was median time to severe crisis elimination. The secondary end points were median time to end-of-crisis, median tramadol consumption, progress of the haemoglobin level over 3 days, side effects, and treatment failure. Results. The age ranged from 14 to 37 years, including 23 women. We noted a beneficial influence of the VEST on the median time to severe crisis (VAS greater than 2) elimination; 17 hours (group 1) against 3.5 hours (group 2) and 4 hours (group 3) with value = 0.0448. Similar significant results were obtained on the diminution of total duration of the crisis (VAS over 0) and median tramadol consumption in patients in the interventional arms. Conclusion. These statistically significant results in the interventional arms suggest that VEST could be an alternative treatment of VOC in sickle cell patients. PubDate: Thu, 04 Feb 2021 15:20:01 +000
Abstract: Introduction. Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods. A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results. There were 56 patients evaluated, of which 39 (70%) received warfarin and 17 (30%) received an OFXai (apixaban or rivaroxaban). Tolerability at 3 months was assessed in 48/56 patients (86%). A total of 34/48 (71%) patients tolerated anticoagulation at 3 months, 12 (80%) in the OFXai arm, and 22 (67%) in the warfarin arm (). There were 10/48 (21%) patients that experienced any bleeding events within 3 months, 7 on warfarin, and 3 on apixaban. Recurrence of thromboembolism within 3 months occurred in 3 patients on warfarin, with no recurrence in the OFXai arm. Discussion. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings. PubDate: Fri, 29 Jan 2021 04:50:01 +000
Abstract: Obesity is increasingly associated with the transformation of monoclonal gammopathy of undetermined significance (MGUS) into multiple myeloma (MM). Obesity, MGUS, and MM share common etiopathogenesis mechanisms including altered insulin axis and the action of inflammatory cytokines. Consistent with this interconnection, metformin could predominantly exert inhibition of these pathophysiological factors and thus be an attractive therapeutic option for MGUS. Despite the possible clinical significance, only a limited number of epidemiological studies have focused on obesity as a risk factor for MGUS and MM. This review describes multiple biological pathways modulated by metformin at the cellular level and their possible impacts on the biology of MGUS and its progression into MM. PubDate: Mon, 18 Jan 2021 14:35:01 +000