Low-dose emicizumab prophylaxis in patients with severe hemophilia A: a retrospective study bringing new hope for our patients.

BACKGROUND: Low-dose emicizumab can potentially offer a cost-effective treatment option in persons with hemophilia A, especially in developing countries. OBJECTIVES: To compare the efficacy and safety of low-dose emicizumab with those on low-dose factor (F)VIII prophylaxis via chart review. METHODS: After ethics approval, chart data of 2 groups of patients were reviewed: group 1 (low-dose emicizumab, n = 10; 3 mg/kg monthly without a loading dose) and group 2 (low-dose FVIII prophylaxis, n = 10; 10-20 IU/kg of FVIII concentrates twice a week). Outcomes were target joints, annual bleeding rate, annual joint bleeding rate, Hemophilia Joint Health Score, nonactivated thromboelastometry-rotational thromboelastometry clotting time, plasma emicizumab levels, and direct costs of treatment. RESULTS: All outcome measures were significantly better in the low-dose emicizumab group than in the low-dose FVIII prophylaxis group. For nonactivated thromboelastometry-rotational thromboelastometry, median values after 6 months in the low-dose emicizumab group were comparable with values seen in patients with mild hemophilia, while the values in the low-dose FVIII prophylaxis group were similar to those of patients with moderate hemophilia. The direct cost of low-dose emicizumab was found to be approximately US $6000 and that for low-dose recombinant FVIII prophylaxis used in our study was US $6282 (the cost may range from US $3432 to $7920 depending on the type of factor) when compared to approximately US $15 000 for standard-dose emicizumab. CONCLUSION: Low-dose emicizumab offers a cost-effective treatment option and can improve access in developing countries. These findings need to be confirmed in a larger and better-controlled study.

Frequency and pattern of chromosomal abnormalities in acute myeloid leukemia from Western India: A retrospective study.

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.

Comprehensive analysis of genetic factors predicting overall survival in Myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of clonal hematological disease with high risk of progression to AML. Accurate risk stratification is of importance for the proper management of MDS. Genetic lesions (Cytogenetic and Molecular mutations) are known to help in prognosticating the MDS patients. We have studied 152 MDS patients using cytogenetics and next generation sequencing (NGS). These patients were evaluated and as per cytogenetic prognostic group, majority (92.1%) of the patients classified as good (81.6%) and intermediate (10.5%) group. The NGS identified 38 different gene mutations in our cohort. Among 111 MDS patients with mutations, the most frequent mutated genes were SF3B1 (25.2%), SRSF2 (19%) U2AF1 (14.4%) ASXL1 (9.9%) RUNX1 (9.9%) TET2 (9%), TP53 (9%), ATM (6.3%), NRAS (5.4%) and JAK2/3 (5.4%). The survival analysis revealed that the mutations in TP53, JAK2/3, KRAS, NRAS and ASXL1 were significantly (P < 0.05) associated with poor survival of the patients. The univariate cox and multivariate cox analysis of our study suggested that the age, marrow morphology, cytogenetic and gene mutations with IPSS-R should be considered for prognosticating the MDS patients. We have proposed M-IPSS-R which changed the risk stratification i.e. 66.3% patients had decreased risk whereas 33.75% showed increased risk compared to IPSS-R. The survival analysis also showed that the M-IPSS-R were more significant in separating the patients as per their risk than the IPSS-R alone. The change in risk stratification could help in proper strategy for the treatment planning.

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature.

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.

The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India.

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.

Mutation profile in Indian primary myelofibrosis patients and its clinical implications.

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.

Wiskott-Aldrich Syndrome Presenting with JMML-Like Blood Picture and Normal Sized Platelets.

Objective. The aim of this paper is to report the case of Wiskott-Aldrich syndrome (WAS) that presented with unusual laboratory features. Clinical Presentation and Intervention. Male neonate admitted with symptoms related to thrombocytopenia, whose initial diagnosis was considered as neonatal alloimmune thrombocytopenia and JMML (juvenile myelomonocytic leukemia) but subsequently diagnosis was confirmed as WAS. Conclusion. This case shows that a suspicion of WAS is warranted in the setting of neonatal thrombocytopenia with JMML-like blood picture and normal sized platelets.

Safety and efficacy of indigenous equine antithymocyte globulin along with cyclosporine in subjects with acquired aplastic anemia.

To confirm the safety and efficacy of an indigenous equine antithymocyte globulin (eATG) along with cyclosporine in Indian subjects with acquired aplastic anaemia. Subjects >2 years old with acquired aplastic anaemia were enrolled at six hospitals between April 2011 and February 2013, after approval from respective Ethics Committees. Equine ATG at a dose of 40 mg/kg/day was infused for 4 days. Efficacy analysis defined a priori, was in subjects, who had completed eATG treatment and followed-up on day 90 and/or 180. Complete response (CR) was defined as-transfusion independent, haemoglobin ≥11 g/dL, absolute neutrophil count (ANC) >1.5 10(9)/L and platelet ≥150 10(9)/L; partial response (PR) was transfusion independent, haemoglobin ≥8 g/dL, ANC >0.5 10(9)/L and platelet ≥20 10(9)/L; non responders were transfusion dependent. Lymphocyte subsets (CD 2, 3, 4 and 8) in the blood were tested on days 0 (pre eATG infusion), 3, 5, 7, 14 and 21 after eATG. Of the 30 subjects (two children <12 years old) enrolled, 19 completed day 90 and 18 completed day 180 visit. Of the remaining 11 subjects, two died on days 12 and 45 due to septicaemia and pneumonia, one was withdrawn after the first dose of eATG due to jaundice and eight were lost to follow-up. The median age was 30 (9-58) years and weight was 57 (26-84) kg. On day 90, 12 of 30 subjects responded (CR 1, PR 11) and 15 of 30 (CR 2, PR 13) on day 180. The most common adverse event was fever related to eATG infusion. There were two serious adverse events (acute renal failure, febrile neutropenia) and both recovered with treatment. There were no unusual adverse events noted during the study period. Blood T lymphocytes showed a mean decrease of 91 % from baseline that recovered by day 21. We conclude that eATG is safe and in combination with cyclosporine showed overall response in 50 % of enrolled subjects. The trial was registered with the clinical trial registry-india (Registration no. CTRI/2012/03/002498).

The Prevalence of Factor V Leiden (G1691A) and Methylenetetrahydrofolate Reductase C677T Mutations in Sickle Cell Disease in Western India.

The prevalence of the Factor V Leiden (FVL; G1691A) mutation and the methylenetetrahydrofolate reductase (MTHFR; C677T) mutation was determined in 180 patients with sickle cell (SS) disease (126 sickle homozygous and 54 sickle ß-thalassaemia--age 1-47 years) and in 130 healthy controls. The FVL mutation in the heterozygous state was present in only 3 patients with SS disease and was absent in the controls. Genotyping of MTHFR 677C > T revealed increased frequency of the C allele than the T allele in patients as well as in controls. This suggests that these genetic markers may not be major risk factors for a hypercoagulable state in Indian patients with SS disease.

FLT3 and NPM-1 mutations in a cohort of acute promyelocytic leukemia patients from India.

BACKGROUND: Acute promyelocytic leukemia (APL) with t (15;17) is a distinct category of acute myeloid leukemia (AML) and is reported to show better response to anthracyclin based chemotherapy. A favorable overall prognosis over other subtypes of AML has been reported for APL patients but still about 15% patients relapse. METHODS: This study evaluated the presence of Famus like tyrosine kinase-3 (FLT3) and nucleophosmin-1 (NPM1) gene mutations in a cohort of 40 APL patients. Bone marrow/peripheral blood samples from patients at the time of diagnosis and follow-up were processed for immunophenotyping, cytogenetic markers and isolation of DNA and RNA. Samples were screened for the presence of mutations in FLT3 and NPM1 genes using polymerase chain reaction followed by sequencing. RESULTS: Frequency of FLT3/internal tandem duplication and FLT3/tyrosine kinase domain was found to be 25% and 7% respectively. We observed a high frequency of NPM1 mutation (45%) in the present population of APL patients.

Hepatosplenic T cell lymphoma.

A 26 year old lady came with intermittent fever since eight months. She also complained of abdominal pain and decreased appetite for six months. She had swelling of feet and distension of abdomen due to ascites since one month. There was history of jaundice one month back. On radiological examination, hepatomegaly with dilated portal vein, massive splenomegaly and ascites without any lymphadenopathy was noted. Chest X-ray was normal. Blood examination and bone marrow studies were inconclusive. We received her liver biopsy, which showed normal architecture and sinusoidal infiltration by a monomorphic population of small to intermediate sized lymphoid cells. Portal tracts were free of such infiltrate. These lymphoid cells were LCA, CD3, CD43 positive and negative for CD20, CD34, CD4, CD8 and c-kit. Based on all these features, a diagnosis of Hepatosplenic T cell lymphoma was made. She was treated symptomatically, however she died within two months of diagnosis.

Myeloproliferative hypereosinophilic syndrome presenting as cardiac failure and response to imatinib.

Idiopathic hypereosinophilic syndrome was first defined by Chursid et al in 1975; however, following the advances in molecular biology, the World Health Organization has proposed a classification in 2008. Hypereosinophilic syndrome is a heterogeneous group of uncommon disorders characterized by marked peripheral eosinophilia and end-organ manifestation. The authors describe a case of sudden-onset cardiac failure in a young individual who had marked peripheral eosinophilia and detection of FIP1L1/PDGFRA fusion gene. A diagnosis of myeloproliferative neoplasm with eosinophilia and eosinophilic endocarditis was made. His clinical and laboratory parameters showed a dramatic response to imatinib and prednisone.

Unusual clinical presentations of familial hemophagocytic lymphohistiocytosis type-2.

BACKGROUND: Mutations of PRF1 gene have been identified in familial hemophagocytic lymphohistiocytosis type-2 (FHL-2) patients, and it has been reported as the commonest gene defect causing FHL. Patients with severe perforin deficiency usually present within first 1 year of life and with severe clinical manifestations. OBSERVATION: We report 4 cases of severe perforin deficiency presenting with delayed onset and unusual clinical presentations viz., B-cell acute lymphoblastic leukemia, the Hodgkin lymphoma, tuberculosis, and the Still disease. Three of these 4 cases showed a common heterozygous missense mutation (p.Trp129Ser). Two of these patients expired because of uncontrolled hemophagocytic lymphohistiocytosis, one patient had 3 relapses while on therapy and one patient was in remission on maintenance therapy. CONCLUSION: This study shows variety of clinical manifestations of perforin deficiency and although the onset of hemophagocytic lymphohistiocytosis is delayed in these patients, the outcome remains poor as in classical severe perforin deficiency patients.

The Fc receptor polymorphisms and expression of neutrophil activation markers in patients with sickle cell disease from Western India.

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 FcγR polymorphisms (FcγRIIA and FcγRIIIB) are considered to influence clinical presentation. This study focuses on distribution of FcγR 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-ß-thalassemia (median age 12 ± 8.58 years) with variable clinical phenotypes along with 175 normals were investigated. FcγRs 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 FcγRIIA and the NA1/NA1 genotype of FcγRIIIB 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 FcγR polymorphisms had significant association with variable phenotypes of sickle cell disease. The expression of CD62L decreased in our patients indicating activation of neutrophils.

Comparison of in-vitro and in-vivo response to fetal hemoglobin production and γ-mRNA expression by hydroxyurea in Hemoglobinopathies.

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.

Effect of CYP2C9 and VKORC1 genetic variations on warfarin dose requirements in Indian patients.

BACKGROUND: Warfarin, an oral anticoagulant is used in patients who are at increased risk of developing blood clots. The management of warfarin therapy is challenging because it shows large inter and intra individual variability in patient response due to factors like age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes. Studies implicate that polymorphisms in VKORC1 and CYP2C9 genes are associated with reduced doses of warfarin. The aim of our current study was to characterize the effects of VKORC1 and CYP2C9 gene variations that contribute to variability in warfarin dosing in Indian patients. METHODS: Genomic DNA was extracted from 103 patients undergoing warfarin therapy. Their mean daily warfarin dose, INR and demographics were recorded and genotyping of VKORC1 and CYP2C9 gene was performed by PCR-RFLP method. RESULTS: Individuals with wild type genotypes required highest mean warfarin dosage of 4.72 mg/day while VKORC1 variants required 3.6 mg/day to maintain their therapeutic INR. CYP2C9*2 genotype was not found to affect the warfarin maintenance dosages. The odds ratio for developing supra therapeutic INR in patients carrying VKORC1 variant allele when compared to wild types was 13.96 (95% CI; 4.85 - 44.65. Other factors affecting warfarin dosages were age and weight. CONCLUSION: Inclusion of pharmacogenetic data along with clinical parameters would help better predict warfarin doses in Indian patients.

Evaluation of danazol, cyclosporine, and prednisolone as single agent or in combination for paroxysmal nocturnal hemoglobinuria.

OBJECTIVE: The responses of 32 patients with paroxysmal nocturnal hemoglobinuria (PNH) were assessed after the patients were put on various combinations of danazol, prednisolone, and cyclosporine. MATERIALS AND METHODS: Nineteen males and 13 females aged between 14 and 60 years with confirmed diagnosis of PNH were treated with danazol (4), danazol + cyclosporine (7), cyclosporine (1), and prednisolone + danazol (20). Response to these interventions was assessed regularly. Danazol was added to cyclosporine in patients with aplastic bone marrow after 3 months of cyclocporine use only unless the former therapy was successful. Four patients with aplastic marrow received only danazol because they had renal insufficiency at presentation. Patients were evaluated with regular complete blood count and routine liver and renal function tests. RESULTS: One patient responded to cyclosporine only. Thirteen of 32 patients (40%) had complete response, 12/32 patients (37%) had partial response leading to freedom from red cell transfusion, and 2/32 (7%) had no response. Five patients (16%) died due to thrombosis or hemorrhage within 3 months of therapy before their response to therapy could be assessed. The median period of review of the cases was 4 years and 6 months. CONCLUSION: Danazol is a useful addition to PNH therapy both in combination with cyclosporine for hypoplastic PNH and with prednisolone for other forms of PNH, and this therapy could be a good alternative where eculizumab and anti-lymphocyte globulin cannot be used for various reasons. CONFLICT OF INTEREST: None declared.

DNA copy number changes and immunophenotype pattern in karyotypically normal acute myeloid leukemia patients from an Indian population.

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.

Cytogenetic and comparative genomic hybridization study of Indian myelodysplastic syndromes.

INTRODUCTION: Myelodysplastic syndromes (MDSs) are clonal stem cell disorders characterized by cytopenias, dysplasia in one or more cell lineages and ineffective hematopoiesis and are associated with significant morbidity and mortality due to bone marrow failure or evolution to acute myeloid leukemia. Clonal chromosomal abnormalities are detected in 40-60% of patients. Multiple recurrent chromosomal aberrations have been identified by cytogenetics including fluorescence in situ hybridization (FISH) which is now widely recognized as one of the most important diagnostic and prognostic markers in MDS. METHODS: Conventional cytogenetics by GTG-banding, FISH, comparative genomic hybridization (CGH) was done on 40 primary MDS subjects. RESULTS: Among 40 subjects, 10 (25%) were abnormal and 30 (75%) showed apparently normal karyotypes with GTG banding and FISH. The various aberrations observed were del 5q-, del 7q-, 20q-, +8. DNA copy number changes including losses (30%) and gains (20%) were detected by CGH in 11 (36.6%) out of 30 karyotypically normal MDS. However chromosome 7 (37%) and 1 (25%) is frequently involved in current study population. CONCLUSIONS: This study confirms that the apart from non-random chromosome aberrations, other chromosome regions also involved in the MDS development. The occupational, environmental and geographical variations might be influencing the disease. Furthermore cytogenetic studies are warranted in larger groups of MDS cases to identify newly acquired chromosome aberrations that may aid in cloning new genes involved in the neoplastic process, ultimately helping in the development of targeted therapeutic drugs.