Jayadev Manikkam Umakanthan

Molecular Insights Into Pathogenesis of Peripheral T Cell Lymphoma: a Review

Purpose of ReviewPeripheral T cell lymphoma (PTCL) is a heterogeneous group of lymphoproliferative neoplasms, with at least 29 distinct entities described in current WHO classification. Using present diagnostic approaches, more than a third of PTCL cases cannot be classified, hence designated as PTCL-not otherwise specified (PTCL-NOS). Herein, we summarize the current genomic findings and their role in the molecular pathogenesis in different PTCL entities.Recent FindingsGene expression profiling (GEP) studies have identified distinct molecular signatures for accurate diagnosis and elucidated oncogenic pathways enriched in major PTCL entities. Furthermore, genomic characterization has identified recurrent somatic mutations and potential therapeutic targets. Further efforts are underway to develop genetically faithful murine models.SummaryGEP studies have identified molecular subgroups of PTCL, characterized by distinct genetic and epigenetic alterations. Understanding the molecular mechanisms of T cell lymphomagenesis using in vivo model will help to reveal novel therapeutic targets.

Lymphomas with pseudo-double hit BCL6-MYC translocations due to t(3;8)(q27;q24) are associated with a germinal center immunophenotype, extranodal involvement, and frequent BCL2 translocations

High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, double-hit or triple-hit lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) rarely occurs in B-cell lymphomas that results in a unique pseudo-double-hit BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92%), including frequent concomitant BCL2 rearrangements (17/24, 71%). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P < .01), had a greater likelihood of extranodal involvement (P < .01), and more frequently appeared triple-hit by FISH analysis (P < .01). Despite presenting with aggressive clinicopathologic features, 100% (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63% (10/16) and 57% (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.

Factors associated with receipt of hematopoietic cell transplantation for acute lymphoblastic leukemia

AIMnTo evaluate practice patterns of hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia.nnnMATERIALS & METHODSnWe utilized the National Cancer Database to extract patient-level data of adults (aged 18-80xa0years) diagnosed with acute lymbhoblastic leukemia between 2003 andxa02012. We performed multivariable logistic regression to determine variables associated with the use of HCT.nnnRESULTSnOut of a total of 11,871 patients, 12.7% received HCT. In a multivariate analysis, older age, male sex, higher Charlson co-morbidity score, nonacademic treatment center, poor education and Medicare/Medicaid or no insurance were associated with lower likelihood of receiving HCT.nnnCONCLUSIONnOur study demonstrates variations in the utilization of HCT based on socioeconomic and health system factors.

A Case of Levamisole-Induced Agranulocytosis

A sixty-eight-year-old male with a past medical history of recurrent cocaine use presented to the emergency department with recurrent diarrhea and was found to have a white blood cell (WBC) count of 1.9u2009×u2009109/L with agranulocytosis (absolute neutrophil count (ANC) of 95u2009cell/mm3). At admission, the patient disclosed that he used cocaine earlier during the day, and a urine drug screen tested positive for this. On hospital day one, the patient was found to have a fever with a maximum temperature of 313.6u2009K. After ruling out other causes and noting the quick turnaround of his neutropenia after four days of cocaine abstinence, the patients neutropenia was attributed to levamisole-adulterated cocaine.

Management of untreated advanced stage follicular lymphoma: Role of patient discernment

Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount.