Manupdesh Singh Sachdeva

Clozapine associated thrombocytopenia

Although agranulocytosis as a side effect of clozapine is well known, there is scarcity of data with regard to thrombocytopenia associated with clozapine. In this report we describe a case of clozapine induced thrombocytopenia and review the existing literature. A 22 year old female patient developed thrombocytopenia while on clozapine 187.5 mg/day for 17 weeks. Thrombocytopenia persisted for 24 weeks even after reduction in the dose of clozapine and ultimately clozapine had to be stopped, which led to resolution of thrombocytopenia. Clozapine-induced thrombocytopenia is a less well-known, but potentially serious, adverse effect that should be screened for in practice. The case highlights the fact that besides monitoring the leucocyte count, platelet count of patients receiving clozapine should also be monitored.

Epstein–Barr Virus Infection Masquerading as Acute Leukemia: A Report of Two Cases and Review of Literature

Epstein–Barr virus (EBV) is the first herpes virus to be completely sequenced. It is implicated in diseases from the benign infectious mononucleosis to malignant nasopharyngeal carcinoma, Burkitt’s lymphoma and primary CNS lymphoma in AIDS patients. It has also been found to be associated with some miscellaneous diseases like chronic fatigue syndrome, multiple sclerosis etc. however causality still remains an issue of debate. As the virus mainly targets the lymphomonuclear cells and the reticuloendothelial system of the body, it’s various manifestations are often mistaken as leukemic malignancies. We report two such cases of young adults who had been diagnosed as having acute leukemia on the basis of atypical cells in the peripheral blood. One patient later turned out to be a classical infectious mononucleosis and second patient had EBV associated hemophagocytic lymphohistiocytosis syndrome.

Hepatosplenic T‐cell lymphoma is a distinct rare entity: Diagnosis by fine‐needle aspiration cytology

In this brief report, we have described the fine‐needle aspiration cytology (FNAC) of a hepatosplenic T‐cell lymphoma (HSTCL) in a 60‐year‐old female patient. The patient complained of fever and heaviness of left upper abdomen. Ultrasound‐guided FNAC of the spleen showed immature lymphoid cells, and a diagnosis of primary non‐Hodgkin lymphoma of spleen was offered. Subsequently, the patient underwent splenectomy and wedge biopsy of liver that confirmed the cytological diagnosis. The lymphoma cells were positive for CD3 immunostain. Primary hepatosplenic T‐cell lymphoma is a rare entity and may often pose diagnostic problems on FNAC. Diagn. Cytopathol. 2010.

High frequency of intermediate and poor risk copy number abnormalities in pediatric cohort of B-ALL correlate with high MRD post induction

Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz., CSF2RA, IL3RA,P2RY8, SHOX region and CRLF2 were analyzed by multiplex ligation dependent probe amplification assay and were detected in 70% (47/67) of cases, with predominantly deletions in CDKN2A/B (36%), PAX5 (18%) and IKZF1 (16%). A statistically significant association of intermediate/poor risk CNAs was noted with high WBC count (p = 0.001), NCI group (p = 0.02) and minimal residual disease at Day35 (p < 0.0001). IKZF1 and CDKN2A/B deletion revealed poor EFS of 56% at 24 months as compared to EFS of 80% in rest of the cases (p = 0.05) suggesting their potential role in early risk stratification.

Deletion of CDKN2A/B is associated with inferior relapse free survival in pediatric B cell acute lymphoblastic leukemia

Abstract Considering conflicting data on CDKN2A/B deletion in ALL, this study to assess its prognostic significance as an independent marker in a total of 96 pediatric B and T-ALL cases was planned. The overall frequency of CDKN2A/B deletion was 44% (n = 43) with 36% (30/83) in B-ALL and 100% (13/13) in T-ALL. CDKN2A/B deletion was significantly associated with high WBC count (p = .002) and National Cancer Institute risk (p = .01) in B-ALL. Importantly, CDKN2A/B deletion cases had poor EFS of 42% at 28 months compared to EFS of 90% in rest (p = .0004). Further, relapse free survival was only 56% for cases with CDKN2A/B deletions (n = 25), compared to 100% in control group (p = .001). Moreover, CDKN2A/B deletion was the only risk factor associated with early relapse (p = .01) compared to IKZF1 deletion (p = .73) or occurrence of BCR-ABL1 fusion transcript (p = .26). Thus our study data highlights potential prognostic role of CDKN2A/B deletions in early disease stratification in pediatric B-ALL.

Chronic Lymphocytic Leukemia With Hodgkin and Reed-Sternberg (HRS) Cells: A Potential Diagnostic Pitfall in Lymph Node Biopsies.

Chronic lymphocytic leukemia (CLL) is known to undergo Richter transformation in a proportion of cases. Transformation into Hodgkin lymphoma has been described in a minority of the cases. However, CLL rarely also shows Hodgkin and Reed-Sternberg cells with a classic morphology and the immunophenotype of Hodgkin lymphoma, even when not in transformation. The presence of these Hodgkin and Reed-Sternberg cells in CLL can cause a diagnostic dilemma.

CLL: Common Leukemia; Uncommon Presentations

We report here a series of ten patients with uncommon presentations and associations of chronic lymphocytic leukemia (CLL) not reported hitherto or occasionally reported in literature. The first two cases describe unusual causes of abdominal distension in CLL and unusual sites infiltration by CLL. The next two cases illustrate occurrence of CLL in association with other hematological malignancies. Cases five and six describe unusual infections and their impact on CLL. Cases seven and eight depict associations of rare non-hematological autoimmune conditions with CLL. The last two cases describe transformation at unusual sites. This series of ten cases illustrates how a common leukemia like CLL can present in different forms and how despite so much progress in understanding of this leukemia so little is known of such presentations.