Current state of non-hematologic cancer-associated thrombosis at a tertiary care hospital in India

Abstract Introduction Cancer-associated thrombosis is a leading cause of morbidity and mortality in malignancy patients. Prophylactic anticoagulation is under-utilized and the cost of low-molecular-weight heparin (LMWH) and direct oral anticoagulants is a major barrier in developing countries. Material and methods A retrospective analysis was performed of all cancer-associated thrombosis patients attending the thrombosis clinic at a tertiary-level referral hospital based in North India between 2011 and 2015. Patient demographics and disease-related parameters were collected and analyzed. Results A total of 771 patients attended the thrombosis clinic during study period, of which 64 cases were malignancy-associated. Of these, 56% of the patients were female and 20% were bedridden. The median age was 48.5 years, adenocarcinoma (48%) being the most common histological subtype. Gynecological malignancies (30%) were the most common malignancies, followed by genitourinary (11%) malignancies. Most of the cases occurred during first year of diagnosis (51%), and only 14% occurred after 3 years. Most of the patients were on combined treatment. Almost 40% of the patients developed thrombosis within 30 days of surgical treatment. Lower limb thrombosis was the most commonly seen type (56%), while abdominal and pulmonary thrombosis were both seen in 5%. Patients were managed with LMWH and vitamin K antagonists (84.3%) and only 6.25% with LMWH alone. Direct oral anticoagulants were not commonly used during the study period. Discussion At the hospital studied, most of the cases occurred early in the disease course. Postoperative prophylaxis could have contributed towards reducing thrombosis in the peri-operative period. Early suspicion and prompt treatment can improve quality of life in such patients.

COVID-19 infection in patients with haematological disease - A tertiary centre experience from north India

This retrospective study was aimed to understand the clinical, laboratory, radiological parameters and the outcome of COVID-19 patients with underlying haematological disease. All patients with known haematological disease admitted with COVID-19-positive status from April to August 2020 in the COVID-19 facility of a tertiary care centre in north India, were included. Their medical records were analyzed for outcome and mortality risk factors. Fifty four patients, 37 males, were included in the study. Of these, 36 patients had haematological malignancy and 18 had benign disorder. Fever (95.5%), cough (59.2%) and dyspnoea (31.4%) were the most common symptoms. Nine patients had severe disease at diagnosis, mostly malignant disorders. Overall mortality rate was 37.0 per cent, with high mortality seen in patients with aplastic anaemia (50.0%), acute myeloid (46.7%) and lymphoblastic leukaemia (40.0%). On univariate analysis, Eastern Cooperative Oncology Group performance status >2 [odd ratio (OR) 11.6], COVID-19 severity (OR 8.2), dyspnoea (OR 5.7) and blood product transfusion (OR 6.4) were the predictors of mortality. However, the presence of moderate or severe COVID-19 (OR 16.6, confidence interval 3.8-72.8) was found significant on multivariate analysis. The results showed that patients with haematological malignancies and aplastic anaemia might be at increased risk of getting severe COVID-19 infection and mortality as compared to the general population

C1236T polymorphism in MDR1 gene correlates with therapeutic response to imatinib mesylate in Indian patients with chronic myeloid leukaemia.

Patients with chronic myeloid leukaemia show an excellent response to treatment with imatinib. However, in some patients, the disease is resistant to imatinib. This resistance may be related to the presence of genetic variations on the drug’s pharmacokinetics and metabolism. We therefore studied three polymorphisms (C1236T, G2677T and C3435T) in the human multidrug-resistance gene (MDR1) in 86 patients with chronic myeloid leukaemia treated with imatinib. Imatinib resistance was more frequent in patients with TT genotype at locus 1236 than in those with CT/CC genotypes (p=0.003). For the other two loci (G2677T and C3435T), resistance was seen to be higher for TT genotype when compared to GG/GT and CT/CC but it was not statistically significant (p=0.13 and p=0.099). In conclusion, determination of C1236T MDR1 genotype may help to predict response to imatinib therapy in patients with chronic myeloid leukaemia. Natl Med J India 2015;28:272–5

Ocular graft versus host disease in allogenic haematopoetic stem cell transplantation in a tertiary care centre in India.

Background & objectives: This study was aimed to report the occurrence of ocular graft versus host disease (oGVHD) in allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients in a tertiary care hospital setting. Methods: A cross-sectional study of ocular surface of allo-HSCT patients was done. Slit lamp biomicroscopy, symptom score, tear meniscus height, fluorescein tear break-up time, Schirmer’s test I, ocular surface staining, dry eye severity, ocular surface disease index score were done. Indications for allo-HSCT, human leukocyte antigen (HLA) matching, GVHD risk factor, systemic manifestation and treatment were also noted. Results: GVHD occurred in 44.4 per cent of 54 allo-HSCT patients (mean age 26.7 ± 12 yr) included in the study. GVHD risk factors identified included female gender, relapse, older age of donor, cytomagelo virus (CMV) reactivation, and multiparous female donors. oGVHD was noted in 31.5 per cent with mean time to occurrence being 17.8 ± 21.9 months after the allo-HSCT and was observed in 89.5 per cent of chronic GVHD cases. Acute GVHD (oral and dermatological) involvement showed a significant association with GVHD in our patients (P< 0.001, 0R 23.0, CI 6.4-82.1). Chronic GVHD was observed to be associated with the occurrence of oGVHD (dry eye) (P<0.001, OR = 24.0, CI 0.02 - 0.29). Of the 34 eyes with oGHVD, dry eye of level 3 severity was seen in 16, level 2 in six, level 1 in 12 eyes. Interpretation & conclusions: GVHD occurred in 44.4 per cent of the patients studied in the present study. Acute and chronic GVHD showed a strong association with oGVHD. Dry eye disease due to chronic oGVHD was observed in 17 (31.5%) of 54 allo-HSCT patient with chronic oGVHD occurring in 17 (89.4%) of chronic GVHD cases in allo-HSCT patients. Our study on oGVHD in post allo-HSCT patients in tertiary care centre points towards the fact that ocular morbidity due to dry eye disease as a result of oGVHD is a cause for concern in these patients.

Correlation of JAK2V617F mutational status in primary myelofibrosis with clinico-hematologic characteristics and international prognostic scoring system scoring: A single center experience.

Introduction: Somatic mutation in the exon 14 of Janus Kinase 2 gene is an established diagnostic marker in bcr-abl negative myeloproliferative neoplasms, especially primary idiopathic myelofi brosis (PIMF). Aim: Our primary aim was to fi nd out the correlation between the JAK2V617F mutational status and the clinico-hematologic characteristics, as well as the international prognostic scoring system (IPSS) scoring of patients with PIMF. Materials and Methods: Clinical and hematologic features were reviewed for 68 patients with primary idiopathic myelofi brosis (PIMF). JAK2V617F mutation status was analyzed by amplifi cation refractory mutation screening-polymerase chain reaction. The patients were further stratifi ed into low, intermediate-1, intermediate-2 and high-risk groups on the basis of IPSS scoring. Results: The JAK2V617F mutation was detected in 58.8% patients. Univariate analysis of variables at presentation identifi ed that JAK2V617F negative patients were signifi cantly associated with more severe anemia (P = 0.045), younger age (P = 0.008), higher transfusion requirement (P = 0.017), and thrombocytopenia (P = 0.015). Patients who were homozygous for JAK2V617F mutation were associated with thrombocytosis (P = 0.014) and also had higher median total leucocyte count (P = 0.20) than the other groups. No signifi cant correlation was detected between JAK2V617F mutational status and the presence of constitutional symptoms, spleen size, grade of bone marrow fi brosis or prognostic risk stratifi cation of the PIMF patients. Conclusion: The variations in the prognostic implication of PIMF patients with mutation status as stated by various publications worldwide, reinstates the need for larger prospective studies using standardized JAK2V617F quantifi cation methods as well as estimation of other newer molecular markers to develop deeper insight into various molecular alterations involving PIMF patients in India as well as worldwide.

Cytogenetic profile of Indian patients with de novo myelodysplastic syndromes.

Background & objectives: Myelodysplastic syndrome (MDS) is a clonal haematopoietic stem cell disorder characterized by ineffective haematopoiesis and leukaemia progression. Cytogenetic analysis has proven to be a mandatory part of the diagnosis of MDS as well as a major indicator for predicting clinical course and outcome. Studies on cytogenetics of MDS are reported mostly from the West and only a few are available from Asian countries. We report herein cytogenetic studies on 40 Indian patients with primary MDS to find out the occurrence and type of chromosome abnormalities and recurring defects. Methods: Cytogenetic analysis was done using GTG banding and karyotyped according to the International System for Human Cytogenetic Nomenclature (ISCN). Results: Of the 40 patients, 19 patients (47.5%) showed clonal karyotypic abnormalities with distribution as follows: 3 of 15 (20%) of refractory anaemia (RA), 4 of 7 (57%) of refractory anaemia with excess blasts-1 (RAEB-1), 4 of 6 (67%) of refractory anaemia with excess blasts 2 (RAEB-2), 2 of 3 (67%) of refractory anaemia with ring sideroblasts (RARS), 2 of 4 (50%) of refractory cytopenia with multilineage dysplasia (RCMD), none (0%) RCMD-ringed sideroblasts (RCMD-RS) and 4 patients with 5q syndrome. The frequent abnormalities observed in our study were -7, 5q-and trisomy 8. Interpretation & conclusions: Two rare chromosomal abnormalities (6q-, 3q-) were found with unknown prognostic significance. Hence, cytogenetic analysis may be incorporated in the routine diagnosis of MDS since there are racial differences in clinical pictures and the molecular events.

Prevalence of JAK2 V617F mutation in Indian patients with chronic myeloproliferative disorders.

Background & objectives: The Janus-associated Kinase-2 mutation JAK2 V617F in chronic myeloproliferative disorders (CMPDs) has been described as a frequent genetic event in majority of patients with polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Its frequency varies in different populations but there are no data from India. We therefore, looked for JAK2 V617F mutation in Indian patients with chronic myeloproliferative disorders. Methods: Mutation screening for JAK2 V617F in patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis was performed in 75 patients attending Haematology clinic in a tertiary care hospital in north India, by polymerase chain reaction and restriction enzyme-based assay. Results: JAK2 V617F mutation was found in 51 of 75 cases (68%) of CMPD, 82 per cent in PV, 70 per cent in ET and 52 per cent of IMF. The presence of JAK2 V617F mutation was associated with a higher haemoglobin level (P<0.05), a higher white blood cell count (P<0.01) and higher age (P<0.05). Interpretation & conclusion: The JAK2 V617F mutation was detected in 86 per cent of patients with CMPD disorders. Peripheral blood mutation screening for JAK2 V617F can be incorporated into the initial evaluation of patients suspected to have CMPD.

Effect of wheat grass therapy on transfusion requirement in beta-thalassemia major.

OBJECTIVE: To assess the efficacy of wheat grass juice on transfusion requirement in patients with beta thalassemia major. METHODS: Fifty-three patients of thalassemia major with a median age of 16 years were given wheat grass juice tablets. RESULTS: The Mean pre and post wheat grass therapy, the pack cell requirement was 288.06 +/- 53.25 gm/Kg/year and 301.25 +/- 54.86 gm/Kg/year (p =0.054) respectively. No adverse effects were noted. CONCLUSION: We conclude that wheat grass therapy for one year is not effective in reducing the transfusion requirement in transfusion dependent thalassemia.

Paroxysmal nocturnal hemoglobinuria in childhood and adolescence--a retrospective analysis of 18 cases.

OBJECTIVE: To assess the clinical and hematological profile of PNH in children. METHODS: Clinical and laboratory features of children with PNH diagnosed in the past six years at our centre were reviewed. Various investigations done included a complete blood count and peripheral smear examination, plasma hemoglobin, urine hemosiderin, acid ham test, sucrose lysis test, immunophenotyping of erythrocytes by sephadex column gel card and of granulocytes by flow cytometry. There were 18 children with a marked male predominance (M 14: F 4). RESULTS: Pallor, jaundice, dark urine and bleeding manifestations were the major presenting complaints. One girl suffered an arterial stroke. All children had cytopenia in at least one cell line. Children were treated with danazol, stanazolol, prednisolone and cyclosporin A variously. Overall response rate was 61%. Children with classical PNH performed slightly better with response rates of 66% (6/9) as compared to aplastic anemia-PNH group which has a response rate of 55% (5/9). Amongst various variables only danazol correlated with better response (p=0.029). CONCLUSION: PNH is an uncommon disease in children and should be included in the differential diagnosis of children presenting with cytopenia.

A case of rhabdomyosarcoma masquerading as acute leukemia at presentation: a case report.

Non-hematopoietic malignancies infiltrating bone marrow have always been a source of erroneous diagnosis. Among these, the small round cell tumors like neuroblastomas and rhabdomyosarcomas mimick the hematopoietic blasts. Several case reports of rhabdomyosarcoma mimicking acute leukemia, clinically and morphologically at presentation have been reported in the literature. To the best of our knowledge such an entity has not been reported in Indian literature. We report here one such case of alveolar rhabdomyosarcoma masquerading as acute leukemia. A thorough clinical examination with high degree of suspicion on bone marrow morphology and judicious use of appropriate immunohistochemistry markers will solve many of these cases.

Therapy-related acute promyelocytic leukemia after treatment of carcinoma breast--a case report.

We report a 43-year-old female, with acute promyelocytic leukemia occurring after 9 months of treatment for carcinoma breast. The diagnosis of APL was made on morphology, cytogenetics and molecular studies. In contrast to other published report of therapy related APL (tAPL) the present case presented early after the primary malignancy and underwent a rapid, downhill course.