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Using thromboelastometry tests incorporated a protocol results in reduction of transfusion requirements in patients undergoing elective combined CABG and valve surgery.Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the ITGA2B/ITGB3 genes is the genetic basis for GT. Establishing a molecular diagnosis is definitive and is important for predictive testing. Using multi-gene panels is an accurate, faster, and cost-effective mode as compared to Sanger sequencing in large genes. We used a targeted resequencing based approach to identify pathogenic variants in eight cases in seven families. These variants were validated using Sanger sequencing in patients as well as family members and were predicted probably pathogenic using in-silico prediction tools. The variants include three missense (3/7 = 43%) (ITGA2Bc.1028 T > C, ITGA2Bc.1186G > A, ITGB3c.1388G > C), two deletions (ITGA2Bc.559delG, ITGA2Bc.3092delT), one duplication (ITGA2Bc.1424_1427dupAGGT) and nonsense variant (ITGA2Bc.2578C > T, p.Gln860Ter). Except for one case which was compound heterozygous, the rest of the cases were homozygous. We found two novel variants that are reported for the first time in GT. The targeted resequencing based approach revealed varied genetic variants in North Indian patients, including two novels ones. The high yield of our panel indicates its suitability for usage in larger cohorts for the genetic diagnosis of GT patients. This approach is cost-effective and less cumbersome as compared to Sanger sequencing for these large size genes with multiple exons. The information so obtained is helpful in prenatal testing, carrier analysis, and genetic counseling.Immune thrombocytopenia (ITP) is a relapsing-remitting disease often requiring more than one line of therapy. Rituximab is a recommended second-line therapy, but the real-world data on its efficacy and safety from resource constraint settings is limited. We aimed to analyze the safety and efficacy of rituximab in ITP. This is a single-center, retrospective study. This study was conducted at a tertiary care hospital in Northern India from 2005 to 2019. On audit of medical records, all patients of ITP (n-513) who had received rituximab (n-81) were screened for inclusion. Patients whose response assessment was not possible were excluded. Finally, 66 patients were analyzed using statistical packages of Python v3.7. The cumulative incidence of overall response on day 20 was 30.61%, and day 30 was 51.72%. The median time to response was 28 day (range 21-51 day). Cumulative incidence of complete response was 16.67%, and partial response 37.88%. After a median follow-up of 789 day (range 181-5260 day), the cumulative incidence of relapse was 30.32%, 36.12%, and 56.57% at 1, 2, and 5 years respectively. There was no effect of age, sex, duration of disease, lines of therapy received, and platelet count on either cumulative incidence of overall response or relapse. ANA positivity was significantly related to the better cumulative incidence of overall response (p = 0.012), but not with relapse. Infusion-related reactions were the commonest adverse event noted (n-4, grade ≥ 3 CTCAEv4). Rituximab and its generic version are safe and effective second line agent in ITP with a good overall response and sustained response.Hemostasis is dependent on sufficient quantity and quality of circulating functional platelets. Platelet function in trauma patients with thrombocytopenia and its impact on the clinical outcome is not adequately explored. Whether platelet dysfunction has a role in the pathogenesis of acute traumatic coagulopathy needs to be studied. Blood samples were collected from 70 thrombocytopenic trauma patients before transfusing platelets and assessed for platelet activation and platelet aggregation using flowcytometry. Primary outcome was in-hospital mortality. Platelet dysfunction was identified in 57.1% of thrombocytopenic trauma patients. A weak inverse correlation between percentage of activated platelets and APTT was observed (Spearman coefficient - 0.25, p = 0.03). A sensitivity and specificity of 66.6% was achieved for a cut off of ≤ 6.5% of platelet activation post trauma with ROC-AUC of 0.658 for identifying coagulopathy. No correlation with mortality however was observed (p > 0.05). Platelet dysfunction had a weak association with coagulopathy suggesting limited contribution of platelet dysfunction in pathogenesis of acute traumatic coagulopathy and warrants further research.The proportion of CD34 + CD38 - CD123 + leukemia stem cells (LSCs) at diagnosis of Acute Myeloid Leukemia (AML) correlated with induction remission (IR), relapse free survival and overall survival in few studies. Prospectively bone marrows of AML patients were immunophenotyped for CD34 + CD38 - CD123 + LSCs at baseline using sequential gating, relevant clinical and laboratory data collected and clinical outcomes were studied.The patients (n = 47) were risk stratified as favorable risk, intermediate risk and adverse risk. The percent of LSCs at baseline in favorable risk group (mean = 13.06%) was significantly less than the adverse (mean = 34.8%, p = 0.027) and the intermediate risk group (mean = 53.2%, p = 0.001). On further analysis, 12 patients attaining IR in intermediate risk group had significantly less LSCs than 15 in non-IR group (mean = 21.18%; range 3-85.6% vs mean = 73.85%; range 12.1-97.9%, p = 0.0002). Of all 47 patients, the proportion of LSCs at baseline was significantly less in those achieving IR (p = 0.024) and correlated with time to response (TTR) (rs = 0.432). Thus to conclude, the proportion of CD34 + CD38 - CD123 + LSCs at diagnosis is less in the favorable than the intermediate and adverse risk groups and is an emerging novel marker for predicting remission in the prognostically diverse intermediate risk group.Waldenstorms Macroglobulinemia (WM) is a rare mature B cell neoplasm characterized by a lymphoplasmacytic lymphoma and an IgM monoclonal protein. It is managed by Rituximab based chemotherapy. A single-centre retrospective study was carried out to analyse the clinical presentation, laboratory features, and treatment outcomes of all consecutive patients of WM, diagnosed over a period of 86 months. First-line treatment regimens included RCD (Rituximab/Cyclophosphamide/Dexamethasone), BDR (Bortezomib /Dexamethasone/ Rituximab) and (Lenalidomide/Dexamethasone). A total of 26 patients of WM were diagnosed during this period, with a median age of 65 years. Majority (89%) of these patients were of intermediate (47%) to high risk (42%). An overall response rate of 76.4% was achieved. RCD was found superior to BDR in terms of treatment response. For those who required 2nd line chemotherapy, the median time to next treatment was 22 months. To conclude, a late presentation and higher risk categories were common in our cohort of patients. Treatment outcome was comparable to those reported in western literature. RCD regimen was found to be a better treatment option in terms of overall survival.

Primary Mediastinal B cell lymphoma (PMBCL) is a biologically and clinically distinct subset of diffuse large B cell lymphoma. We analysed the outcomes of our cohort of PMBCL patients treated with Dose adjusted (DA)-R-EPOCH regimen.

This is a retrospective analysis of consecutive PMBCL patients who received chemotherapy consisting of DA-R-EPOCH with filgrastim support. Survival analysis was done using Kaplan-Meier method. All calculations were performed using SPSS version 20 for windows.

A total of 43 consecutive suspected PMBCL patients were reviewed for this study, 6 patients were excluded as diagnosis of PMBCL could not be established. All patients except one (97.3%) received 6 cycles of R-DA-EPOCH regimen. Median age of the patients was 27years (range 15-58). Bulky disease (> 7cm) was present in 97% patients and 54% patients had extranodal disease. With a median follow up of 40months, 3-year overall survival was 80.6% (95% CI 74.0-87.2). CD532 solubility dmso The 3-year event free survival was 78.4% (95% CI 71.6-85.2). There were 6 (16.2%) relapses, 1 (2.7%) primary progression and 7 (23%) deaths. Mediastinal radiotherapy was administered to 17 (45.9%) patients. All the deaths were due to disease progression. Grade III/IV toxicities were seen in 28 (75.7%) patients, febrile neutropenia being the most common one.

DA-R-EPOCH regimen is an effective and tolerable regimen in PMBCL patients even with adverse features.

DA-R-EPOCH regimen is an effective and tolerable regimen in PMBCL patients even with adverse features.Epstein Barr virus (EBV) associated Hodgkin lymphoma (HL) has been defined as cases with clonal EBV infection, EBV genome and gene products in the Reed Sternberg cells. We evaluated the prevalence and clinico-pathological association of EBV in North Indian HL patients. Eighty-eight cases of histologically confirmed classic HL were evaluated for EBV by both IHC expression of LMP1 and real time PCR on formalin fixed lymph node tissue. The expression pattern was analyzed for any association with clinical and histomorphological parameters. Nodular sclerosis subtype was seen in 79.5% patients and mixed cellularity was seen in the remaining patients. Ninety percent of the cases were positive for EBV. The detection rate of EBV by IHC was higher. The EBV positive cases presented with higher disease stage (p  0.05). In our study population a high proportion of HL cases showed positivity for EBV indicating a pathogenic role. The positivity was independent of age, gender and histological subtype. Further evaluation of EBV positivity in modulation of tumor immunity may provide insights into variable treatment outcome in EBV positive cases.Risk-stratification has contributed to a dramatic improvement in survival in pediatric acute lymphoblastic leukemia (ALL). This study evaluated the utility of prephase response and day 15 bone marrow when a minimal residual disease (MRD) assessment was available. A file review of children aged ≤ 15 years diagnosed with precursor-B ALL from 2014 to 2019 was performed. The protocol used for risk stratification and treatment was based on a UKALL-2003 backbone. All patients received one week of prephase therapy comprised of intravenous dexamethasone in the first 48 h followed by oral prednisolone. The median age of the 255 patients in the study was 5 years. Following the prephase, the peripheral blood absolute blast count was 0 and ≥ 1000/µL blasts in 141 (56%) and 29 (11%), respectively. Ten of 199 (5%) patients with an evaluable day 15 bone marrow had M3 status. At the end of induction, 30 (12%), 127 (50%) and 98 (38%) patients belonged to the standard-risk, intermediate-risk and high-risk (HR) groups, respectively. An M3 day15 bone marrow was the sole reason for escalation in three (3%) of the patients in the HR group. A lack of complete clearance of peripheral blood blasts post-prephase [HR 2.45 (1.04-5.75), p = 0.040] and a positive MRD [HR 3.00 (1.28-7.02), p = 0.011] independently predicted risk of relapse. Complete blast clearance is superior to the traditional cut-off of 1000/µL in predicting relapse. The role of a day 15 bone marrow morphology is diminished when an end of induction MRD is available.