Distribution of common BCR-ABL fusion transcripts and their impact on treatment response in Imatinib treated CML patients: A study from India

Background: Philadelphia chromosome (Ph): Hallmark of CML is caused by reciprocal translocation between chromosomes 9 and 22 resulting in BCR-ABL fusion protein. Most commonly associated breakpoint with CML is M-bcr in exon 13 or exon 14, producing splice variant b2a2 or b3a2 respectively. The distribution of these transcripts and their influence on clinico-hematological parameters is variable. Impact of the fusion transcripts on treatment outcome in Imatinib treated CML patients is still a matter of debate. Aims/settings and design: We conducted this study on 400 CML-CP patients to look for the distribution of fusion transcripts i.e. b3a2 and b2a2, their clinico-hematological profile and impact on treatment response in patients treated with Imatinib. Material and Methods: CML-CP was diagnosed by reverse transcriptase PCR (RT-PCR) for the BCR-ABL fusion transcript. Real-time quantitative PCR (RQ-PCR) was performed on peripheral blood every 3-6 monthly to look for treatment response. Results: The overall frequency of b3a2 transcript was observed in 288 (72%) followed by b2a2 in 104 (26%) and hybrid fusion transcript (b3a2 + b2a2) was seen in 8 (2%) cases. MMR was attained in 198/288 (68.7%) patients with b3a2 transcript and 90/288 (31.3%) patients failed to achieve MMR after 12 months of Imatinib therapy. Among the patients with b2a2 transcript, 44/104 (42.3%) patients achieved MMR and 60/104 (57.7%) patients failed to achieve MMR after 12 months of Imatinib therapy. Conclusions: In conclusion, the frequency of b3a2 transcript was more as compared to b2a2 transcript. MMR was significantly higher in patients with b3a2 transcript as compared to patients with b2a2.

Expect the unexpected – Loss of surface CD3 on flow cytometry in hepatosplenic T-cell lymphoma: An eye opener

Hepatosplenic T-cell lymphoma (HSTCL) is a rare extranodal T-cell lymphoma that shows preferential sinusoidal infiltration of spleen and liver. It usually shows bright expression of surface CD3 (sCD3) with restriction for γδ-T cell receptors (TCR). We present a case of a 34-year-old male who presented with hepatosplenomegaly and B symptoms. His peripheral blood and bone marrow (BM) was involved by atypical lymphoid cells that were CD2+, CD7+, CD56+, cytoplasmic CD3+, and sCD3− on immunophenotyping by flow cytometry. As sCD3 is a lineage marker for T-cell lymphomas, the loss of sCD3 posed a diagnostic dilemma. However, typical pattern of sinusoidal BM and liver involvement by CD3+ cells and TCR gene rearrangement positivity led to final diagnosis of HSTCL. The differential diagnosis, workup, and clinical course of the case are discussed. To the best of our knowledge, only one case of de novo HSTCL with negative sCD3 has been reported before in the literature.

Clinico‑hematological profile and outcome of acute promyelocytic leukemia patients at a tertiary care center in North India.

OBJECTIVES: Acute promyelocytic leukemia (APL) is the only acute leukemia amenable to targeted therapy. However, there is limited Indian data on APL. We aimed to analyze data of APL patients treated with all trans retinoic acid (ATRA) and anthracycline based chemotherapy. MATERIALS AND METHODS: A total of 34 cases of APL were treated at our center over 4 years. Induction chemotherapy consisted of a combination of ATRA and daunorubicin. RESULTS: Most of our patients were intermediate risk (50%) followed by high risk (41.17%). Induction mortality was 14.7%. We observed a high incidence of febrile neutropenia (91%) and 50% of our patients developed ATRA syndrome. Four patients (11.76%) relapsed during follow‑up (median ‑ 15 months, range: 13‑33 months). There was no correlation between risk status and death or relapse or ATRA syndrome. Median event free survival (EFS) duration was not reached however mean duration was 38.45 ± 3.84 months. Median overall survival (OS) duration was also not reached at 53 months of follow‑up. The 4 year OS and EFS were 75.45% and 64.5% respectively. On multivariate analysis, only disseminated intravascular coagulation (DIC) significantly correlated with a poor OS and EFS. DISCUSSION: Our data reflects that APL remains a highly curable malignancy with good response to ATRA plus anthracycline based chemotherapy even with a greater number of high and intermediate risk patients. Only DIC during induction chemotherapy bore an impact on survival in our patients.

Clinico-biologic profile of Langerhans cell histiocytosis: a single institutional study.

CONTEXT: Langerhans cell histiocytosis (LCH) is a rare atypical cellular disorder characterized by clonal proliferation of Langerhans cells leading to myriad clinical presentations and highly variable outcomes. There is a paucity of Indian studies on this subject. AIM: To present the experience of management of LCH at a single institution. SETTINGS AND DESIGN: This is a retrospective observational study of patients with LCH who presented at the Tata Memorial Hospital between January 1987 and December 2002. MATERIALS AND METHODS: Fifty-two patients with LCH were treated in the study period. Due to the long observation period and variability in diagnostic and therapeutic protocols, the patients were risk-stratified based on present criteria. The disease pattern, management approaches and treatment outcomes of patients were recorded. STATISTICAL ANALYSIS USED: Statistical analyses were done using Student's 't' test, test for proportion and survival estimates based on the Kaplan-Meier method. RESULTS: The median age at presentation was 3 years and more than 48% of the patients had Group I disease. Skeleton, skin and lymphoreticular system were the commonly involved organs. Majority (80%) required some form of therapy. The projected overall survival is 63% at 10 years and mean survival is 118 months. Seventeen percent of surviving patients developed long-term sequelae. CONCLUSIONS: The clinico-biologic profile of LCH patients in India is largely similar to international patterns except a higher incidence of lymphoreticular involvement. Majority of the patients respond favorably to therapy and have a good outcome, except a subset of Group I patients who warrant enrollment in clinical trials with innovative therapeutic strategies to improve outcome.

Correlates of tobacco-use pattern amongst adolescents in two schools of New Delhi, India.

BACKGROUND: As adolescent tobacco use has been found to be a major predictor of future use, preventive efforts need to be focused on this section of population. OBJECTIVES: To assess the role of knowledge regarding tobacco, risk-taking attitude, peers, and other influencers on tobacco and areca nut use, amongst adolescents. SETTINGS AND DESIGN: A school-based cross-sectional study covering two schools. Students of classes IX and XI, of selected schools, participated in the study (n = 596). METHODS: A pretested and validated, close ended, self-administered questionnaire was used. Sociodemographic factors, awareness regarding tobacco, risk-taking attitudes, role of peers and other influencers, and tobacco, areca nut and alcohol use, were studied. STATISTICAL ANALYSIS: Point estimates, 98% Confidence Intervals, tests of significance, bivariate and multivariate analysis (multiple logistic regression). RESULTS: Almost 42% of tobacco users started before the age of 12 years. Peer pressure, general stress, and media were important influencers. Logistic regression analysis showed that students in public school were using more tobacco [Odds ratio (OR) = 1.85, P = 0.174] and tobacco/areca nut (OR = 1.14, P = 0.02). The difference in use between the genders and class in which studying was statistically not significant. Lesser proportion of those possessing adequate knowledge regarding tobacco used it as compared to those without adequate knowledge (OR = 0.13, P < 0.001) however, possession of adequate knowledge was not a good predictor of areca nut consumption (OR = 0.86, P = 0.585). The most important correlate for tobacco use (OR = 6.41, P < 0.001) and areca nut use (OR = 11.17, P < 0.001) was risk-taking attitude. CONCLUSION: Multi-pronged and concerted efforts targeting children at an early age are required to prevent tobacco and areca nut use among adolescents.

Intra-abdominal extralobar pulmonary sequestration presenting antenatally as a suprarenal mass.

Extralobar pulmonary sequestration is a rare pulmonary parenchymal anomaly which rarely may be present in an intra-abdominal location. The authors report a case of intra-abdominal extralobar pulmonary sequestration which presented to us as an antenatally diagnosed suprarenal mass and was worked up as such. The diagnosis was revealed only at laparotomy. Intra-abdominal extralobar pulmonary sequestration should also be kept in differential diagnosis in cases of masses in the suprarenal location, especially on the left side.

Injection practices in a metropolis of North India: perceptions, determinants and issues of safety.

BACKGROUND: At least 50 percent of the injections administered each year are unsafe, more particularly in developing countries, posing serious health risks. An initial assessment to describe injection practices; their determinants and adverse effects can prevent injection-associated transmission of blood borne pathogens by reducing injection frequency and adoption of safe injection practices. AIMS: To assess the injection practices in a large metropolitan city encompassing varied socio-cultural scenarios. STUDY SETTING AND DESIGN: Field based cross sectional survey covering urban non-slum, slum and peri-urban areas of a large metropolitan city. METHODS AND MATERIAL: Injection prescribers, providers and community members selected by random sampling from the study areas. Pre tested questionnaires assessed knowledge and perceptions of study subjects towards injections and their possible complications. Observation of the process of injection and prescription audit also carried out. STATISTICAL ANALYSIS: MS Access for database and SPSS ver 11 for analysis. Point estimates, 95% confidence intervals, Chi Square, t test, one-way ANOVA. RESULTS: The per capita injection rate was 5.1 per year and ratio of therapeutic to immunization injections was 4.4:1. Only 22.5%of injections were administered with a sterile syringe and needle. The level of knowledge about HIV and HBV transmission by unsafe injections was satisfactory amongst prescribers and community, but inadequate amongst providers. HCV was known to a very few in all the groups. The annual incidence of needle stick injuries among providers was quite high. CONCLUSION: A locally relevant safe injection policy based on multi disciplinary approach is required to reduce number of injections, unsafe injections and their attendant complications.