Summary: The duodenal juice and fecal aerobic microflora was investigated in 54 patients with persistent diarrhea (age ≤2 years). The duodenal aspirates yielded increased aerobic bacteria (>105 organisms/ml) in 28 (51.9%) of the patients. Established enteric pathogens were isolated from the duodenal aspirates of 12 (22.2%) of the 54 patients, viz., enteroadherent Escherichia coli (EAEC) (5), enterotoxigenic E. coli (ETEC) (3), enteropathogenic E. coli (EPEC) (1), nontyphoidal Salmonella (1), and Giardia lamblia (2). The total aerobic bacterial count was >105 in all 12 patients positive for specific pathogens apart from one case in whom E. coli showing diffuse adherence to HEp-2 cells were identified. Among the remaining 42 specific pathogen-negative patients, 19 (45.2%) also had >105 aerobic organisms/ml in the small bowel. Eight strains of Klebsiella from four of the patients were negative for enterotoxin production in a rabbit ileal loop assay and for adherence to HEp-2 cells. In contrast, 28/54 (51.9%) of the same patients had known enteric pathogens in their stools, viz., nontyphoidal Salmonella (8 or 14.8%), Shigella (2 or 3.7%), Campylobacter (1 or 1.9%), ETEC (4 or 7.4%), EPEC (2 or 3.7%), EAEC (7 or 13.0%), and G. lamblia and Entameba histolytica (3 or 5.6%). Further search for potential virulence factors among aerobic bacteria colonizing the upper small intestine in persistent diarrhea is warranted.
Acute promyelocytic leukemia (APML) is a well-characterized malignancy with typical clinico-hematological and molecular features. However, Indian data on this malignancy are limited. This study was conducted to determine the clinico-hematological profile of APML in India. Thirty-five patients with APML presenting to Hematology Department, AIIMS, New Delhi, between July 2003 and June 2005 were evaluated for presenting clinical features, hemogram, peripheral smear, bone marrow morphology and cytochemistry. Reverse transcriptase PCR (RT-PCR) for PML-RARα was done in all cases. Male-to-female ratio was 0.9:1 (males - 17 and females - 18) with median age 25 years (range 11-57 years). Presenting features included anemia, bleeding, fever, gum hypertrophy and scrotal ulceration. All cases showed hypergranular abnormal promyelocytes. Median hemoglobin was 6.3 g/dL (range - 3.0-9.0 g/dL), total leukocyte count (TLC) was 33.88 × 10 9 /L (range - 1-170 × 10 9 /L). Platelet count was 28 × 10 9 /L (range - 4-170 × 10 9 /L). All cases were positive for myeloperoxidase and sudan black (SB), whereas 60% cases also showed non specific esterase (NSE) positivity with 40% cases being fluoride sensitive. RT-PCR showed PML-RARα in 33/35 cases with the bcr3 isoform being present in 24/33 positive cases (72.7%). The two cases negative for PML-RARα showed typical morphology and responded to ATRA. On statistical analysis, no correlation was found between bcr isoform and TLC, platelet count, age sex and early death. Unusual features included gum hypertrophy and scrotal ulceration at presentation and high median presenting TLC (33.8 × 10 9 /L). There was, however, no microgranular variant. Another interesting feature was a high incidence of NSE positivity (60%), which was fluoride sensitive in 40%. Moreover, the bcr3 isoform was significantly overexpressed (72.7%) in comparison to other studies. APML in India has certain unusual features, which may reflect a different biology.
Background: FLT3-ITD and NPM1 mutations are considered to be the major determinants of the patient response to therapy and outcome. The primary aim of this study was to establish the correlation between these molecular mutations and the clinico-hematologic parameters as well as the prognostic outcome of the Indian acute myeloid leukemia (AML) patients. Materials and Methods: This prospective study involved newly diagnosed nonpromyelocytic AML patients who had undergone complete diagnostic workup, including immunophenotyping, conventional cytogenetics and molecular analysis for NPM1 and FLT3-ITD mutation by reverse transcriptase polymerase chain reaction at presentation. Results: Overall, the prevalence of NPM1 and FLT3-ITD mutations was found to be 14.4% and 10.8%, respectively. Among patients with normal karyotype, leukocytosis was significantly associated with NPM1+ group than the NPM1− group (P = 0.0019) and more severe degree of anemia was observed in the FLT3-ITD+ patients than the other groups (P = 0.025). No significant correlation was found in terms of age at presentation (P = 0.56), sex ratio (P = 0.467), median platelet count (P = 0.27), and blast percentage between NPM1+ and FLT3-ITD+ groups. Complete remission (CR) rates were better in the NPM1+/FLT3-ITD− group than the other three groups. Unlike most other studies, improved CR rates as well as disease-free survival were observed in the NPM−/FLT3-ITD− group than the FLT3-ITD+ groups although not reaching statistically significant levels. Conclusion: Some differences in the clinical behavior of the Indian AML patients in comparison to that of the West in the presence of NPM1 and FLT3-ITD suggests that comprehensive studies are required to confirm the definitive role of these mutations among AML patients, especially with normal karyotype.
This retrospective analysis of 254 children less than 15 years of age treated with MCP-841 protocol from June 1992 to June 2002 was undertaken to identify the pattern of relapse and determine management lacunae. Two hundred twenty-three (87.8%) children achieved a complete remission of whom 40 (17.9%) relapsed. The mean age of relapsed patients was 6.5 years. The male/female ratio was 9:1. There were 23 (57.5%) isolated bone marrow (BM), 7 (17.5%) isolated central nervous system (CNS), 2 (5%) isolated testicular, 5 (12.5%) BM+testes and 1 each of BM+CNS, CNS+testes, and isolated bone relapses. Twenty-seven children (67.5%) relapsed on-therapy whereas 13 (32.5%) relapsed posttherapy. All 9 CNS relapses occurred on-therapy whereas 5/8 (62.5%) of testicular relapses occurred posttherapy. Lymphadenopathy was the only significant predictor for relapse. High-risk features such as age less than 1 year and greater than 10 years (P=0.047) and white cell count greater than 50.0 x 10(9)/L (P=0.044) were significantly more frequent in patients with early on-therapy relapse than in patients with off-therapy relapse. The overall survival in the entire study cohort was 67+/-3.5%. Modest survival outcome, relapse while on chemotherapy and the higher incidence of CNS and testicular relapse indicate the need for reappraisal of our treatment protocol. There is a need of identifying risk factors and high-risk groups in our set of patients and risk-stratified intensification of chemotherapy in them.
Elevated JAK2V617F allele burden is associated with enhanced expression of downstream target genes in Philadelphia negative chronic myeloproliferative neoplasms (CMPNs) which include PV, ET & PMF. Previous studies have shown the impact of JAK2V617F allele burden on clinical phenotype of CMPNs. However, there is no data from India regarding the association between JAK2V617F allele burden and clinical phenotype in PV.We aimed to investigate the effect of allele burden on clinical phenotype in 90 JAK2V617F positive PV patients and to see its influence on disease related complications.Allele burden of 90 JAK2V617F positive PV patients was quantified by Real-time polymerase chain reaction (RQ-PCR).74/90 (82.22%) were males and 16/90 (17.78%) were females (median 45 years, range 35-78). Patients with age >50 years had significantly higher JAK2V617F allele burden (median 40.15%, range 0.49-91.62 %) than patients with ≤ 50 years age (median 48.59 %, range 0.56-86.74 %; P < 0.032). Patients with splenomegaly had significantly higher JAK2V617F allele burden (mean 50.24%, range 6.91-84.17%) than patients without splenomegaly (mean 33.82 %, range 0.49-71.83 %; P < 0.017). Patients with higher allele burden (median 57.20, range 43.4-72.03%) had significantly raised thrombotic events than the patients with lower allele burden (median 37.38, range 0.49-84.17%; P < 0.043). 49/90 (54%) were homozygous and 41/90 (46%) were heterozygous.Higher JAK2V617F allele burden showed association with increased age, splenomegaly and thrombotic events. Thus, it may be considered for prognostication and setting up the treatment protocol in PV patients.
'%3e%3ccircle r='20' fill='%23008'/%3e%3ccircle r='17.5' fill='%23fff'/%3e%3ccircle r='3.5' fill='%23008'/%3e%3cg id='d'%3e%3cg id='c'%3e%3cg id='b'%3e%3cg id='a' fill='%23008'%3e%3ccircle r='.875' transform='rotate(7.5 -8.75 133.5)'/%3e%3cpath d='M0 17.5.6 7 0 2l-.6 5L0 17.5z'/%3e%3c/g%3e%3cuse xlink:href='%23a' transform='rotate(15)'/%3e%3c/g%3e%3cuse xlink:href='%23b' transform='rotate(30)'/%3e%3c/g%3e%3cuse xlink:href='%23c' transform='rotate(60)'/%3e%3c/g%3e%3cuse xlink:href='%23d' transform='rotate(120)'/%3e%3cuse xlink:href='%23d' transform='rotate(-120)'/%3e%3c/g%3e%3c/svg%3e)
