Haematologica最新文献

Not available.

Not available.

Not available.

Not available.

Not available.

Not available.

Age and sex have historically been associated with differences in acute lymphoblastic leukemia (ALL) survival. In the NOPHO ALL2008 trial, patients aged 1-45 years with BCR::ABL1-negative B-precursor and Tcell ALL were included, but neither sex nor age was integrated into risk group allocation. Among 1,771 trial patients stratified into protocol-appropriate risk groups, we estimated the impact of age and sex on survival (even after relapse) and toxicities prospectively registered at three-month intervals. In multivariate Cox regression analysis adjusted by sex, age group, and risk group, age but not sex was an independent risk factor for reduced 5-year event-free survival (EFS), hazard ratio 1.57 (95%CI 1.15-2.14) for patients 10-17.9 years, and 2.70 (2.03-3.58) for patients 18-45 years, compared to patients.

Although chronic lymphocytic leukemia (CLL) is diagnosed by identifying a circulating B-cell clone that exceeds 5x106/μL, additional distinct clones (ADC) have been identified in various studies. Notably, the numbers of ADC documented in these studies has increased as the various technologies evolved. To better define the frequency and the characteristics of ADCs in CLL, we used a Next Generation Sequencing (NGS) platform that affords high sequencing depth along with steps that limit overcounting to analyze IGHV-IGHD-IGHJ gene rearrangements in circulating CD5+ B cells from 57 patients. Notably, all patients had at least one ADC, in addition to the clinically relevant clone (CRC)., in 46 patients for whom lymphocyte count data were available, 44 had at least one ADC above the threshold of 1 B cell/μL, and remarkably, the average number of ADCs was 12 per patient. Notably, in two patients, the predominant ADC (pADC) qualified clinically as a separate CLL clone and in the in the remaining cases as low/high-count monoclonal B-cell lymphocytosis (MBL) clones. Moreover, in 11 patients studied longitudinally, pADCs were persistent and often increased in number. ADCs in patients with CLL exhibited fourfold more stereotyped IGHV-IGHD-IGH rearrangements than found in CD5+ B cells from healthy individuals, and IGHV use, somatic mutations, and Ig isotype distribution was similar between pADCs and CRCs. Thus, finding multiple expanded clones within the CD5+ B cells is the rule in patients with CLL, indicating that leukemogenesis is a multiclonal process that likely involves competition among B cells with special BCR features.

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment landscape for hematologic malignancies. However, it is frequently complicated by immune effector cell-associated hematotoxicity (ICAHT), a potentially life-threatening adverse event encompassing neutropenia, anemia, and thrombocytopenia. These cytopenias elevate the risk of severe infections, transfusion dependence, and prolonged hospital stays, contributing substantially to morbidity and non-relapse mortality. This review delineates the incidence, mechanisms, and risk factors for ICAHT, highlighting the complex interplay between disease burden, patient immune status, and CAR-T product features. Standardized grading systems, based on the depth and duration of neutropenia, have improved ICAHT classification and enabled more consistent risk stratification. Current prophylactic and therapeutic strategies ranging from growth factor administration to hematopoietic stem cell boosts for refractory cases are discussed, emphasizing tailored approaches to mitigate severe and prolonged hematotoxicity. These management strategies highlight the need for targeted interventions to prevent ICAHT without compromising CAR-T efficacy. As CAR-T therapy broadens to new indications, optimized ICAHT management could enhance patient outcomes, reduce healthcare utilization, and increase therapy accessibility.

Not available.