Search

Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors. We report, a 14-yearold boy who presented with clinical features of aplastic anemia (AA). Subsequent bone marrow examination and multiparametric flowcytometric immunophenotyping revealed an evolving hypoplastic acute myeloid leukemia. Chromosomal breakage studies using clastogenic agent mitomycin C showed 88% stress induced chromosomal/chromatid breaks, gaps and rearrangements revealing an underlying FA. The case emphasizes upon the role of a systematic clinico-investigative approach in diagnosing such patients who by clinical criteria appear to have idiopathic AA and appear phenotypically normal. A timely and accurate diagnosis becomes vital in these cases to implement appropriate therapy. [ABSTRACT FROM AUTHOR]

We report a case of bevacizumab- (BEV-) induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin) regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) regimen along with BEV 10mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the 13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets. [ABSTRACT FROM AUTHOR]

Background & objectives: Diagnosis of myelodysplastic syndromes (MDS) is subjective in low-grade cases with <5 per cent blasts or <15 per cent ring sideroblasts. Flow cytometry (FCM) has been used to diagnose MDS; but, it still has only an adjunctive role. This study was conducted to evaluate the role of FCM to diagnose MDS and correlate the number of aberrancies with revised international prognostic scoring system (R-IPSS). Methods: This study included 44 consecutive clinically suspected cases of MDS with refractory cytopenia(s) and 10 controls. Patients were divided into two groups: (i) proven MDS cases (n=26), and (ii) suspected MDS (n=18). Ogata quantitative approach, pattern analysis and aberrant antigen expression were studied. Results: Ogata score =2 correctly diagnosed 80.7 per cent (21/26) while aberrant antigen and pattern analysis with flow score of =3 could diagnose 92.3 per cent (24/26) patients with proven MDS. Combination of both with flow score =3 could diagnose 100 per cent patients. Eight patients in suspected MDS group with persistent cytopenia on follow up were labelled as probable MDS. Ogata score =2 was present in 5 of 8 and pattern analysis score =3 was present in six probable MDS patients. Combination of both with flow score =3 was present in seven of eight patients. Spearman's correlation between Ogata score and R-IPSS, pattern analysis and R-IPSS and combination of both scores and R-IPSS showed significant positive correlation in proven MDS as well as when proven and probable MDS patients were combined. Interpretation & conclusions: Our results showed that combined Ogata approach and pattern analysis, demonstration of =3 aberrancies in >1 cell compartment could diagnose most MDS patients. Patients with high flow scores had high R-IPSS scores. Patient with flow score =3 and borderline cytomorphology should be observed closely for the development of MDS. [ABSTRACT FROM AUTHOR]

Introduction: Antiplatelet resistance is one of the urgent issues in current stroke care. One-third to one-half of the patients who experience a recurrent stroke is already on antiplatelet medications. We studied resistance to aspirin and clopidogrel in Indian stroke patients and its association with gene polymorphisms. Methods: Platelet function testing by light transmission aggregometry was performed on 65 patients with ischemic stroke who were stable on dual antiplatelet therapy (clopidogrel 75 mg OD and aspirin 75 mg OD) along with 65 age-matched controls. Aspirin resistance was considered as mean platelet aggregation ≥70% with 10 μM adenosine diphosphate (ADP) and ≥20% with 0.75 mM arachidonic acid. Clopidogrel resistance was defined as <10% decrease from the baseline in platelet aggregation in response to ADP 10 μM and semi-response as <30% decrease from the baseline. Polymorphisms CYP2C19 * 2 and GPIIb/IIIa (PLA1/A2) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Results: We found 64.6% (42/65) patients with inadequate response to clopidogrel (15.4% [10/65] resistant and 49.2% [32/65] semi-responders) and 4.6% (3/65) patients with inadequate response to aspirin (3.1% [2/65] resistant and 1.5% [1/65] semi-responder). The frequency of CYP2C19*2 mutant genotype was significantly higher in clopidogrel nonresponders compared to responders (P = 0.014). Clopidogrel nonresponsiveness was much higher in small vessel stroke. Conclusion: Unlike aspirin, a high proportion of nonresponders to clopidogrel was identified. In an interim analysis on 65 Indian patients, a significant association was found between CYP2C19*2 and clopidogrel nonresponsiveness. [ABSTRACT FROM AUTHOR]

Introduction: Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia, characterized by anemia, jaundice, and splenomegaly. The diagnosis of HS relies on symptoms of hemolysis, a family history of HS, and a positive laboratory test which is usually the osmotic fragility test (OFT). We conducted a study to assess the utility of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean sphered cell volume (MSCV), and mean reticulocyte volume (MRV) in the diagnosis of HS and if these are helpful in distinguishing cases of HS from immune hemolytic anemia. Methods: A total of 102 patients suspected to have HS were enrolled. In addition 10 cases of immune hemolytic anemia (IHA) were included in the study and performance of the above screening tests was evaluated. The diagnosis of HS was based on incubated OFT, eosin 5′- maleimide (EMA) dye binding test, and flowcytometric OFT. Results: A total of 29 patients were diagnosed as having HS. The sensitivity and specificity for diagnosis HS by MCHC > 35 g/dL was 44.82%, and ΔMCV−MSCV > 10 fL has a sensitivity and specificity of 82.75% and 95.9% for diagnosis of HS. Using an algorithm of ΔMCV−MSCV > 10 fL and ΔMRV−MSCV < 25, for the differentiation of HS from IHA had sensitivity of 68.9% and specificity of 98.8%. [ABSTRACT FROM AUTHOR]

Background: Monoclonal light chain gammopathies are uncommon subsets of plasma cell disorders which usually present as diagnostic challenge. Materials and Methods: Twenty cases of monoclonal light-chain gammopathy were identified after screening 150 plasma cell disorders at a tertiary care referral center of North India and were analyzed for clinical profile and treatment outcomes. Results: Out of 20 cases of monoclonal light-chain gammopathy, 65% (13/20) were light-chain multiple myeloma (LCMM) type, 20% (4/20) were light-chain deposition disease (LCDD) type, and 15% (3/20) had primary amyloidosis (AL). Renal failure (65% of cases) was the most common presentation. All the patients with LCDD presented with renal failure (4/4) while as 61% of LCMM (8/13) and 33% of AL (1/3) presented with renal failure. Five patients presented with anemia and all were LCMM type. Two patients presented with lytic bone lesions (LCMM type) and one patient presented with plasmacytoma (LCMM). Overall response rate after 4 cycles of induction therapy was 92.3% in LCMM group, 100% in LCDD group, and 33.33% in AL group (excluding one patient who expired before the start of treatment). LCMM showed 23% partial remission (PR), 30.77% very good PR, 38.46% complete response (CR), and 5% no response (NR). LCDD showed PR 75% and CR 25%. AL showed PR 33.33% and NR 5%. Conclusions: Renal failure is a common presentation of monoclonal light chain gammopathies, and it should alert the treating physician for the underlying uncommon plasma cell disorder. [ABSTRACT FROM AUTHOR]

Background: The use of novel agents for induction prior to autologous stem cell transplantation (ASCT) has considerably improved the complete response (CR) rate in multiple myeloma (MM) patients. There are very few studies from the developing countries on the use of novel agents followed by ASCT. Aims and Objectives: The current study was aimed for retrospective evaluation of the efficacy and response rates of induction with bortezomib (Velcade) plus dexamethasone (VD regimen) followed by ASCT in Indian patients. Materials and Methods: Ten patients with newly diagnosed, symptomatic MM who had received four cycles of VD induction before stem cell collection were evaluated. High dose melphalan was given for conditioning followed by stem cell transfusion. Thalidomide or lenalidomide was used as post-transplantation maintenance treatment. Results: Post VD induction, the overall response rate (ORR) was 90% including 20% CR, 40% very good partial response (VGPR), and 30% partial response (PR). Post ASCT, the ORR was 100%, including 80% CR and 20% VGPR. The 5-year overall survival and progression free survival rates were 65.6% and 57.1%, respectively. Conclusions: The VD induction regimen was effective and well tolerated in this retrospective analysis of Indian patients with newly diagnosed MM. It significantly improved the post-induction and post-transplant response rates without affecting stem cell collection. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Flow Cytometry Rapidly Identifies All Acute Promyelocytic Leukemias With High Specificity Independent of Underlying Cytogenetic Abnormalities" by H. Y. Dong et al. in a 2011 issue.

Background: Interpreting hemoglobin high performance liquid chromatograms with borderline HbA 2 values is often problematic, especially in antenatal cases if the partner is a known thalassemia trait. Methods: We tested for underlying β-thalassemia mutations in 25 subjects with borderline HbA 2 values (between 3.0%-4.0%). Amplification refractory mutation system (ARMS-PCR) was used to detect the five common Indian β-thalassemia mutations: (IVS-I-5 (G>C), IVS-I-1 (G>T), codons 8/9 (+G), codons 41/42 (-TTCT) and 619 bp deletion). β-Globin gene sequencing was performed if no mutation was detected. Results: A β-globin gene defect was identified in 8 (32%) of the 25 cases with HbA 2 levels ranging from 3.5%-3.9%. ARMS-PCR revealed IVS-I-5 (G>C) in three, 619 bp deletion in two and codons 41/42 (-TTCT) in one case. Two cases had CAP +1 (A>C) mutation on gene sequencing. IVS-I-1 (G>T) and codons 8/9 (+G) were not found in this small cohort. Conclusions: Mutation analysis should be offered to all at-risk couples with borderline HbA 2, especially those with values between 3.5% and 4.0% and microcytic hypochromic indices. Significant mutations different from those in other ethnic populations were seen in this small institution-based study. [ABSTRACT FROM AUTHOR]

Discusses research on MDRI mRNA expression in young patients with acute lymphoblastic leukaemia (ALL) at presentation and in nine relapsed cases. Methodology; Results of the study; Relevance of P-glycoprotein/MDRI1 mRNA expression in vitro and in clinical drug resistance in young ALL patients.