ABSTRACT
Background@#The clinical phenotype of hemophilia A (HA) does not always correlate with severity.Similarly, the presence of inhibitors does not necessarily increase the risk of bleeding.This paradox between clinical and laboratory findings may be partially attributed to non-modifiable factors, such as blood group, which is known to influence FVIII levels in healthy individuals. Our aim was to assess the effect of ABO blood group antigens on FVIII levels across the severity spectrum of HA and risk of inhibitor development. @*Methods@#Data of consecutive patients with HA who visited the coagulation unit of a northern Indian tertiary care hospital between 2010‒2021 were reviewed. Patients with missing blood group data, transfusion histories, or baseline FVIII levels were excluded. @*Results@#Mild, moderate, and severe HA was present in 41 (6.9%), 72 (12.2%), and 479 (80.9%) patients, respectively. There were no differences in the FVIII levels among the various blood groups across the HA severity spectrum. Inhibitors were administered to 35 patients (5.9%). In the multivariate analysis, blood group A was an independent risk factor for the development of inhibitors (adjusted odds ratio 2.70, P =0.04) after adjusting for age at onset of bleeding, FVIII transfusion, age at first FVIII transfusion, and severity of HA. @*Conclusion@#Unlike what is observed in healthy individuals, blood group did not influence residual FVIII levels across the severity spectrum of HA. Patients in group A had a higher risk of developing inhibitors.
ABSTRACT
Background@#This study evaluated the outcomes of patients with refractory/relapsed Hodgkin lymphoma (RRHL) treated with a bendamustine-based regimen in combination with ifosfamide, etoposide, and vinorelbine (VIBE). @*Methods@#Consecutive RRHL patients who were treated with the VIBE regimen were identified and studied for clinicopathologic characteristics, response to VIBE regimen, event-free survival (EFS), and feasibility of an autologous stem-cell transplant (autoSCT). @*Results@#In total, 24 patients received the VIBE regimen, and a median of 3 cycles were administered. In this cohort, 80% of the patients had received ≥2 prior lines of therapy. The overall and complete response rates with VIBE were 79% and 42%, respectively. After a median follow-up (following VIBE regimen) of 14 months (range, 3‒76), the 3-year EFS and OS were 46% and 74%, respectively. Of the eligible patients, 92% underwent successful AutoSCT. The mean CD34+ cell count in the autograft was 5.5×106/kg (SD 2.07). Neutropenia was the commonest hematologic toxicity and it was observed in 42% of the patients. However, only 9% of the patients developed grade III/IV febrile neutropenia. Chemotherapy-induced nausea and vomiting were the second most common grade III/IV toxicities in our cohort of patients. @*Conclusion@#In this retrospective analysis, the combination regimen, VIBE, has shown good efficacy in heavily pre-treated patients with RRHL without compromising stem cell collection. These encouraging results provide a rationale for further development of this regimen.
ABSTRACT
Background@#Platelet aggregation studies using conventional light transmission aggregometry (LTA) have several disadvantages and require strict pre-analytical measures for reliable results.We aimed to examine the utility of flow cytometric platelet aggregation (FCA) assay in detecting platelet function defects (PFDs) in patients with a history of bleeding symptoms. @*Methods@#Sixty-four participants (24 patients and 40 healthy controls) were included in this study.LTA and FCA assay were performed simultaneously in patients and healthy controls. In the FCA assay, two portions of platelets from the same individual were labeled separately with CD31-FITC and CD31-PE. After mixing and stimulation with agonists, the double-colored platelet aggregates were visualized using a flow cytometer. The results generated using the two techniques were compared and correlated. @*Results@#The patients’ median age was 17 years (range, 3‒72 yr) with a male-to-female ratio of 1:1.7. There was substantial agreement between LTA and FCA assay in detecting a PFD (κ=0.792). Four patients showing a Glanzmann thrombasthenia-like pattern on LTA exhibited an abnormal FCA. A functional defect in collagen binding was detected on the FCA assay conducted in two immune thrombocytopenic patients with severe bleeding. @*Conclusion@#FCA assay can be used to identify functional defects in platelets, with potential applications in thrombocytopenic individuals. It also facilitates the diagnosis of inherited bleeding disorders with platelet defects.
ABSTRACT
Background@#This study evaluated the outcomes of patients with refractory/relapsed Hodgkin lymphoma (RRHL) treated with a bendamustine-based regimen in combination with ifosfamide, etoposide, and vinorelbine (VIBE). @*Methods@#Consecutive RRHL patients who were treated with the VIBE regimen were identified and studied for clinicopathologic characteristics, response to VIBE regimen, event-free survival (EFS), and feasibility of an autologous stem-cell transplant (autoSCT). @*Results@#In total, 24 patients received the VIBE regimen, and a median of 3 cycles were administered. In this cohort, 80% of the patients had received ≥2 prior lines of therapy. The overall and complete response rates with VIBE were 79% and 42%, respectively. After a median follow-up (following VIBE regimen) of 14 months (range, 3‒76), the 3-year EFS and OS were 46% and 74%, respectively. Of the eligible patients, 92% underwent successful AutoSCT. The mean CD34+ cell count in the autograft was 5.5×106/kg (SD 2.07). Neutropenia was the commonest hematologic toxicity and it was observed in 42% of the patients. However, only 9% of the patients developed grade III/IV febrile neutropenia. Chemotherapy-induced nausea and vomiting were the second most common grade III/IV toxicities in our cohort of patients. @*Conclusion@#In this retrospective analysis, the combination regimen, VIBE, has shown good efficacy in heavily pre-treated patients with RRHL without compromising stem cell collection. These encouraging results provide a rationale for further development of this regimen.
ABSTRACT
Background@#Platelet aggregation studies using conventional light transmission aggregometry (LTA) have several disadvantages and require strict pre-analytical measures for reliable results.We aimed to examine the utility of flow cytometric platelet aggregation (FCA) assay in detecting platelet function defects (PFDs) in patients with a history of bleeding symptoms. @*Methods@#Sixty-four participants (24 patients and 40 healthy controls) were included in this study.LTA and FCA assay were performed simultaneously in patients and healthy controls. In the FCA assay, two portions of platelets from the same individual were labeled separately with CD31-FITC and CD31-PE. After mixing and stimulation with agonists, the double-colored platelet aggregates were visualized using a flow cytometer. The results generated using the two techniques were compared and correlated. @*Results@#The patients’ median age was 17 years (range, 3‒72 yr) with a male-to-female ratio of 1:1.7. There was substantial agreement between LTA and FCA assay in detecting a PFD (κ=0.792). Four patients showing a Glanzmann thrombasthenia-like pattern on LTA exhibited an abnormal FCA. A functional defect in collagen binding was detected on the FCA assay conducted in two immune thrombocytopenic patients with severe bleeding. @*Conclusion@#FCA assay can be used to identify functional defects in platelets, with potential applications in thrombocytopenic individuals. It also facilitates the diagnosis of inherited bleeding disorders with platelet defects.
ABSTRACT
BACKGROUND: Sympathetic activation is associated with congestive heart failure (CHF) and leads to adverse clinical events.We hypothesized that meditation by reducing emotional reactivity would have beneficial effect in reducing arrhythmias compared to control patients. METHODS: Patients known to have CHF and implantable cardioverter defibrillators (ICD) were randomized to Vipassana meditation or usual care control group. Meditation group underwent meditation classes three times during the first week, thereafter every once two weeks. They were encouraged to practice meditation at least once everyday. The ICD was followed by clinic/ remote visits. Atrial (AA) and ventricular arrhythmias (VA) as well cardiac events were assessed in follow up. Chi square test was used to compare nominal variables and t test for continuous variables. RESULTS: Patients (n=25, 65% male, mean LVEF 25%, HTN 38%, Diabetes 12%, coronary artery disease 38%, NYHA class 2.2) were followed for 79 + 36 months. Comparing meditation vs control, survival was higher (88%vs 67%); there was less cumulative sustained AF episodes (mean 0.9, IQR 0-1 vs 2.5, IQR 2-4, p=0.045), sustained VT occurred (25% vs 55%, amiodarone use (none vs 44%), and VT ablation in 6.6% vs 33% in the meditation group. CONCLUSIONS: In this first pilot study of meditation in CHF patients with ICD, during long term follow up, there is a trend for improved survival and reduced arrhythmias in patients randomized to meditation.
ABSTRACT
ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.
ABSTRACT
Background@#Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, which is attributed to differences in the genetic characteristics of the leukemic clone. We studied the genomic profile of 52 treatment-naïve CLL patients. @*Methods@#Genetic analysis was performed by multiplex ligation-dependent probe amplification (MLPA) using the SALSA P038 Probemix (MRC Holland, Amsterdam), which contains probes for 2p (MYCN,ALK,REL), 6q, 8p (TNFRSF10A/B), 8q (EIF3H,MYC), 9p21 (CDKN2A/B), 10q (PTEN), 11q (ATM, RDX, PPP2R1B, CADM1), chromosome 12, 13q14 (RB1, DLEU1/2/7, KCNRG, MIR15A), 14q, 17p (TP53) and chromosome 19, and for NOTCH1 7541-7542delCT, SF3B1 K700E, and MYD88 L265P mutations. @*Results@#The median age was 65 years (male:female=2:1). The median hemoglobin, total leukocyte, and platelet counts were 12.4 g/dL, 57.7×10 9 /L, and 176.5×10 9 /L, respectively. At least one genetic abnormality was observed in 34 (65%) patients. The most common abnormality was del(13q14) (deleted DLEU2 and DLEU1/RB1 genes), which was observed in 22 (42%) cases, followed by trisomy 12 [7 (13%) cases]. Del(11q) (deleted ATM, RDX11/PPP2R1B-4) and del(17p) (deleted TP53) were present in 5 (10%) and 2 (4%) cases, respectively. 19p13.2 (CDKN2D-2) amplification and NOTCH1 mutation were found in one case each. @*Conclusion@#Genetic abnormalities are commonly (65%) observed in CLL patients. Del(13q), which is associated with DLEU2 andDLEU1/RB1 gene deletion, was the most common.Compared with other abnormalities, del(11q) and del(17p) patients presented with cytopenia and higher Binet stage, while those with del(13q14) had a longer time to first treatment.
ABSTRACT
Serum and urine protein electrophoresis and immunofixation are essential for identification and categorization of M protein/monoclonal protein. Based on the number of discrete bands identified the condition can be a monoclonal, biclonal or triclonal gammopathy. A subset of cases show an interesting pattern on immunofixation electrophoresis, with a complete immunoglobulin molecule, along with excess free light chains where in one light chain band shows similar mobility as the heavy chain, while the other light chain band of same isotype has a different mobility. Over a 3 year study period, 420 immunofixation electrophoresis gels were studied to select the cases with the typical pattern as described. The clinical records where searched for data of baseline evaluations done prior to starting therapy, including clinical presentation, biochemical parameters, hemogram and bone marrow examination. Twenty cases (4.7%) were identified from the records, of these 77.8% cases had renal impairment and 33.3% presented with rapidly progressive renal failure. The possible explanation is the toxic effects of excess free light chains, in our cohort. The bound LCs show mobility similar to the HC bands on serum immunofixation gels, however the free light chains, exist in polymeric forms and show a different mobility. The identification and reporting of this pattern provides additional information regarding the high load of light chains, and indicates that patient may have a poor renal outcome/performance.
ABSTRACT
No abstract available.
Subject(s)
Leukemia, Hairy Cell , Leukemia, Lymphocytic, Chronic, B-CellABSTRACT
No abstract available.
Subject(s)
Humans , Clonal Evolution , Leukemia, Myelogenous, Chronic, BCR-ABL PositiveABSTRACT
Agranulocytosis as a side effect of clozapine has been reported to be associated with initial phases of treatment, i.e., first six months. Agranulocytosis with clozapine during the initial phases of treatment has been linked to genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes. However, there is limited literature on late onset agranulocytosis with clozapine and this has very rarely been linked to human leukocyte-antigen haplotypes vulnerability. In this report we review the existing data on late onset agranulocytosis with clozapine and describe the case of a young man, who developed agranulocytosis with clozapine after 35 months of treatment and was found to have genetic vulnerability in form of being positive for HLA DR4. This case highlights underlying autoimmune immune mechanism in clozapine-induced agranulocytosis and the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with genetic vulnerability to develop this condition.
Subject(s)
Humans , Agranulocytosis , Clozapine , Granulocyte Colony-Stimulating Factor , Granulocytes , Haplotypes , NeutropeniaABSTRACT
BACKGROUND: Plasma cell leukemia (PCL) is a rare and aggressive plasma cell neoplasm. In PCL, clonal plasma cells comprise ≥20% of the peripheral blood (PB) leukocytes and/or the absolute clonal PB plasma cell count is ≥2×10(9)/L. Primary PCL (PPCL) originates de novo, whereas, secondary PCL (SPCL) evolves from pre-existing multiple myeloma. METHODS: Clinicohematological features, immunophenotypic profile, and survival of PCL patients were analyzed retrospectively. RESULTS: Between January 2007 and December 2014, ten PPCL and four SPCL patients were investigated (8 PPCLs and 3 SPCLs had complete clinical data). All were North Indians, sharing common geography and ethnicity. Our cohort showed less frequent renal failure, more frequent hepatomegaly, and non-secretory type disease. In contrast to western literature, flow cytometric immunophenotyping of our cohort revealed altered expression of CD138 (67%), CD56 (33%), and CD20 (0%). With novel therapeutic agents, these PPCL patients had a median overall survival of 15 months. CONCLUSION: We highlight that our PPCL patients from North India had distinct clinicohematological and immunophenotypic profiles. The significance of our findings must be tested in a larger patient cohort and must be supported by molecular and cytogenetic investigations to unmask possible significant effects on pathogenesis.
