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Context: Chromosomal abnormalities play an important role in diagnosis and prognosis of hematological diseases. Aims: The aim of the present study was to study the pattern and frequency of chromosomal aberrations in acute myeloid leukemia (AML) subgroups from western India. Settings and Design: A retrospective study was conducted through evaluating laboratory proforma which were filled during 2005 to 2014 for diagnosis and treatment of AML subjects. Methods and Material: We have studied chromosomal aberrations in 282 subjects with AML from western India. AML patients were sub‑grouped according to FAB classification. Cytogenetic study using conventional cytogenetics (GTG‑banding) and Fluorescence in situ hybridization (FISH) was carried out using FISH probes (AML1/ETO, PML/RARA, CBFB). Statistical analysis: Student’s t test for continuous variables and Pearson’s Chi‑squared test for categorical variables were used to identify the relationship between variables. Results: Cytomorphological study revealed AML‑ M3 as most frequent (32.3%) group followed by AML‑M2 (25.2%) and AML‑M4 (19.9%). Chromosomal abnormalities were identified in 145 (51.42%) of the total AML cases. A high frequency (38.6%) of chromosomal abnormalities was identified in AML‑M3 subgroup as compared to AML‑M2 (31%) and AML‑M4 (20.6%). Conclusions: Cytogenetic study is important for the diagnosis and management of the AML patients. Our study identified chromosomal abnormalities in AML subgroups with varied frequencies. It is important in diagnosis and monitoring of the disease. As younger AML patients were more affected in our study, etiological factors such as environmental factors need to be studied. Combination of conventional cytogenetics and FISH has an advantage of identifying high frequency of chromosomal aberrations in AML patients. [ABSTRACT FROM AUTHOR]

Introduction: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. Aim: To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD Methods: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. Results: The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6–12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma‐associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab. Conclusion: In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD. [ABSTRACT FROM AUTHOR]

Byline: Suchitra. Swaminathan, Swati. Garg, Manisha. Madkaikar, Maya. Gupta, Farah. Jijina, Kanjaksha. Ghosh Background: Acute promyelocytic leukemia (APL) with t (15;17) is a distinct category of acute myeloid leukemia (AML) [...]

Byline: Khushnooma. Italia, Farah. Jijina, Rashid. Merchant, Suchitra. Swaminathan, Anita. Nadkarni, Maya. Gupta, Kanjaksha. Ghosh, Roshan. Colah Background: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely [...]

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Abstract: Objectives: Hydroxyurea is known to reduce ineffective erythropoiesis and thereby hemolysis leading to a reduction in bilirubin levels in patients with hemoglobinopathies. However, the effect of hydroxyurea on hyperbilirubinemia in relation to the UGT1A1 gene promoter polymorphism is not known in Indian patients with different hemoglobinopathies. Design and methods: We studied 112 patients (77 sickle cell anemia, 22 β-thalassemia intermedia and 13 HbE-β-thalassemia) who were on hydroxyurea therapy for 2years for their response towards hyperbilirubinemia associated with UGT1A1 promoter polymorphism. Results: The patients with (TA)7/(TA)7 repeats had significantly higher serum bilirubin levels than those with (TA)6/(TA)6 repeats in all the groups and the reduction in serum bilirubin after hydroxyurea therapy was still higher among patients with (TA)7/(TA)7 repeats when compared with (TA)6/(TA)6 repeats. Conclusions: Higher bilirubin levels were associated with the (TA)7/(TA)7 sequence however they did not come down to normal levels after hydroxyurea therapy. [ABSTRACT FROM AUTHOR]

A 28 year old female patient presented with refractory anaemia since childhood and recurrent still-births at 28-30 weeks of gestation. One still-born child was hydropic at birth. Bone marrow showed characteristic morphological changes in congenital dyserythropoietic anaemia (CDA)-Type III. Electron microscopy showed disruption of the nuclear membrane, spongy appearance of nuclei, stacks of microtubules in intermediate normoblasts and myelin figures in erythroid cells. In vitro culture and karyotype data from the bone marrow of the patients is presented. Recurrent still-births in association with congenital dyserythropoietic anaemia has rarely been reported in the literature. [ABSTRACT FROM AUTHOR]

Objective. Sickle cell disease has variable clinical manifestations. Activation of neutrophils plays an important role in the initiation and propagation of vaso occlusive crises which can be analysed by determining the expression of neutrophil antigens such as CD16, CD32, and CD62L. The common FcyR polymorphisms (FcyRIIA and FcyRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcyR polymorphisms and their association with neutrophil activity among the patients from western India. Methods. In this paper 127 sickle cell anemia patients and 58 patients with sickle-β-thalassemia (median age 12 ± 8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcyRs polymorphisms were analysed by RFLP and AS-PCR. Activation of neutrophils was measured by flow cytometry. Results. The genotypic frequency of the H/R genotype of FcyRIIA and the NA1/NA1 genotype of FcyRIIIB was significantly decreased in patients compared to normals (P-0.0074, P-0.0471, resp.). We found a significant difference in the expression of CD32 and CD62L among the patients as against normals. A significantly higher expression of CD32 was seen in the milder patients with the H/H genotype (P-0.0231), whereas the expression of CD16 was higher in severe patients with the NA2/NA2 genotype (P-0.0312). Conclusion. The two FcyR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils. [ABSTRACT FROM AUTHOR]

Background & objectives: Myelodysplastic syndrome (MDS) represents a group of clonal haematologieal disorders characterized by progressive cytopenia reflecting defects in erythroid, myeloid and megakaryocytic maturation. The incidence of MDS is more in older age groups and frequent chromosome abnormalities reported to be monosomies 5 and 7. However, the data on cytogenetic changes in Indian MDS patients are scanty. The present study was therefore undertaken to study the aetiolo~' and frequency of chromosomal changes in MDS patients, attending a tertiary care hospital in Maharashtra, India. Methods: The study was carried out in 145 MDS patients for six years (2001-2006) at National Institute of Immunohaematology (ICMR), and KEM Hospital, Mumbai, India. The patients were diagnosed according to FAB and WHO classification. Cytogenetic study was carried out using GTG-banding and fluorescence in situ hybridization (FISH) methods. Statistical analysis was done with χ² and Fisher's exact test. Results: Chromosomal abnormalities, including novel chromosome aberrations were detected in 54.48 per cent MDS patients and frequency of chromosomal aberrations increased with increase in age (≥30 yr). Among occupational exposure factors, chromosomal aberrations significantly (P<0.05) associated with pesticides exposure. Interpretation & conclusion: Our findings showed 54.48 per cent chromosome abnormalities including novel chromosome aberrations in MDS patients and these chromosome aberrations were increased with advancing age. In our series a high frequency of younger population (53%) developed M DS, a detailed molecular genetics and aetiological factors need to be studied. [ABSTRACT FROM AUTHOR]

Describes severe aplastic anemia (SAA) as a relatively rare disorder of hemopoietic stem cell deficiency. Implication of etiological agents in the pathogenesis of AAS; Correlation of ethiopathogenesis with the clinical outcome; Diagnosis of patients with SAA on the basis of pancytopenia and hypocellular bone marrow.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11 , and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11 , and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified., Competing Interests: RV was employed by the company Medgenome, Pvt. Labs, Bangalore, India. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shabrish, Kelkar, Yadav, Bargir, Gupta, Dalvi, Aluri, Kulkarni, Shinde, Sawant-Desai, Kambli, Hule, Setia, Jodhawat, Gaikwad, Dhawale, Nambiar, Gowri, Pandrowala, Taur, Raj, Uppuluri, Sharma, Kini, Sivasankaran, Munirathnam, Vedam, Vignesh, Banday, Rawat, Aggarwal, Poddar, Girish, Chaudhary, Sampagar, Jayaraman, Chaudhary, Shah, Jijina, Chandrakla, Kanakia, Arora, Sen, Lokeshwar, Desai and Madkaikar.)

Background: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by abnormal proliferation of megakaryocytes, bone marrow fibrosis, and extramedullary hematopoiesis. We did mutation profile of 50 patients of PMF and tried to correlate it with initial clinical presentation of these patients., Materials and Methods: All new and follow up patients who were diagnosed as PMF based on WHO 2016 definition of PMF were included. Mutation profile of these patients including JAK2 V617F, JAK2 exon 12, CALR and MPL mutations was done and all clinical, demographic and laboratory details were recorded., Results: Total 50 patients were enrolled out of which 29 were males and 21 were females. Out of these patients, 32 (64%) were JAK2 positive, 13 (26%) were CALR positive, 1 (2%) were MPL positive and 4 (8%) were triple negative. As compared to JAK2+ve patients and triple negative group, CALR positive patients were younger, had lower total leucocyte count, larger spleen size, lower dynamic international prognostic scoring system (DIPSS) score and higher grade of fibrosis of marrow., Conclusion: This study depicts that incidence of JAK2 and CALR mutations in Indian PMF patients is fairly similar to that in rest of the world. CALR positive patients have better clinical parameters at presentation and have better prognosis as compared to JAK2 positive patients., Competing Interests: There are no conflicts of interest.

Background: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the only drug widely used in different hemoglobinopathies; however, the response is very variable. We compared the efficacy of hydroxyurea in-vitro in erythroid cultures and in-vivo in the same patients with different hemoglobinopathies to induce HbF production and enhance γ-messenger RNA expression., Materials and Methods: A total of 24-patients with different Hemoglobinopathies were given hydroxyurea and their response was studied in-vivo and in-vitro on mononuclear cells collected from them simultaneously., Results: A total of 57.7% of patients (responders) showed no further crisis or transfusion requirements after hydroxyurea therapy with a mean increase in fetal cells (F-cells) of 63.8 ± 59.1% and γ-mRNA expression of 205.5 ± 120.8%. In-vitro results also showed a mean increase in F-cells of 27.2 ± 24.7% and γ-mRNA expression of 119.6% ± 65.4% among the treated cells. Nearly 19.0% of the partial-responders reduced their transfusion requirements by 50% with a mean increase in F-cells of 61.2 ± 25.0% and 28.4 ± 25.3% and γ-mRNA-expression of 21.0% ± 1.4% and 80.0% ± 14.1% in-vivo and in-vitro respectively. The non-responders (15.3%) showed no change in their clinical status and there was no significant increase in F-cells levels and γ-mRNA expression in-vivo or in-vitro., Conclusion: Thus, this method may help to predict the in-vivo response to hydroxyurea therapy; however, a much larger study is required.

Chromosomal abnormalities are important in the diagnosis and prognosis of patients with acute myeloid leukemia (AML). The purpose of this study was to identify DNA copy number variations in karyotypically normal AML patients and their correlation with immunophenotypes. Conventional comparative genomic hybridization (CGH) and immunophenotyping were performed in 46 untreated AML patients aged 7-68 years. Among the 86 Indian patients who had AML, 40 (46.5%) showed an abnormal karyotype and 46 (53.4%) showed no chromosome aberrations. The karyotypically abnormal AML patients were excluded from the study. Out of the 46 patients without chromosomal aberrations, 24 (52.2%) showed DNA copy number variations including losses and gains. The DNA copy number variations involved chromosomes 1, 3, 6, 12, 15, 16, 17 (gains) and 1, 4, 2, 3, 5, 7, 8, 9, 10, 11, 13, 15, 18, 20, 21 (losses). The aberrant immunophenotype was noticed in 13 of these 24 (54%) cases. The hidden chromosome rearrangements in karyotypically normal AML, which could not be detected by conventional cytogenetics and fluorescence in situ hybridization, were detected by CGH. These genetic changes have an important role in the prognosis of the disease. The DNA copy number changes might also be involved in the aberrant immunophenotypes in our study.