Bone Marrow Transplantation最新文献

Allogeneic haematopoietic cell transplantation (allo-HCT) remains the only potentially curative option for patients with myelofibrosis (MF), yet the integration of JAK inhibitors (JAKi) and novel agents into transplant pathways has created increasing complexity. To capture current real-world practice, the EBMT Chronic Malignancies Working Party conducted a survey of 19 high-volume European centres performing MF allo-HCT. Most centres (68%) routinely initiated JAKi, primarily ruxolitinib, in transplant-eligible patients prior to conditioning, with goals of splenomegaly reduction and symptom control. Management of ruxolitinib intolerance or resistance was heterogeneous, with strategies including switching to alternative JAKi, proceeding directly to allo-HCT, or enroling in clinical trials. Peri-transplant approaches also varied: over half of centres continued ruxolitinib throughout conditioning, while others employed tapering or abrupt discontinuation. Experience with newer JAKi and investigational therapies was limited. Post-transplant, most centres did not routinely reintroduce JAKi, although some used them for relapse or GVHD mitigation. Notably, many centres reported transplant delays due to prolonged medical therapy, with adverse consequences including disease progression. These findings highlight significant heterogeneity in practice, which is likely to increase as more novel agents are integrated in treatment algorithms. Harmonised, multidisciplinary guidelines to optimise timing and outcomes for MF patients eligible for allo-HCT are needed.

Mutations in the DNMT3A gene are not yet classified as a distinct prognostic group in the latest European Leukemia Net (ELN) 2022 genetic risk classification of AML. We analyzed 1888 adult AML patients with ELN 2022 intermediate- or poor-risk cytogenetics who received their first allo-transplant in first complete remission between 2015 and 2022. Among patients with cytogenetically normal AML, the triple-positive mutation group (DNMT3A, NPM1, and FLT3-ITD) was the most frequent (n = 340, 29%), while DNMT3A co-occurrence with either FLT3 or NPM1 mutations alone was less common (4% and 9%, respectively). Patients with DNMT3A mutations were less likely to have a secondary AML (14% versus 24%, p < 0.001). DNMT3A mutations negatively affected post-transplant leukemia-free survival (LFS) in patients with normal karyotype and NPM1 mutation without FLT3-ITD (2-year LFS: 70% versus 90%, hazard ratio [HR]: 3.3, p = 0.006), and increased relapse incidence (RI) in FLT3-ITD and wild-type NPM1 subgroup (2-year RI: 30% versus 18%, HR: 2.32, p = 0.03). Notably, patients with normal karyotype and triple-positive mutation exhibited excellent 2-year LFS and OS (61% and 70%), indicating that allo-transplant overcomes the dismal outcome of this group. The impact of DNMT3A mutations on post-transplant outcomes in AML patients in first remission varies based on karyotype and co-mutations.

Patients with relapsed/refractory multiple myeloma (R/R MM) receiving chimeric antigen receptor (CAR) T-cell therapy are at high risk of toxicities, including cytokine release syndrome (CRS). The roles of positron emission-tomography computed tomography (PET/CT) in predicting these toxicities remain unclear. We retrospectively studied 62 patients with R/R MM who received B-cell maturation antigen (BCMA) CAR T-cell therapy at our center. Baseline metabolic tumor volume (MTV) of more than 107.2 cm³ and total lesion glycolysis (TLG) exceeding 406.5 were classified as high MTV and high TLG, respectively. Both high MTV (P = 0.008) and high TLG (P = 0.011) were identified as independent risk factors for the development of severe CRS classified as grade 3 to 4. Moreover, the administration of tocilizumab for the treatment of CRS was associated with high MTV (P = 0.005) or high TLG (P = 0.010). Notably, our multivariate Cox models that incorporated either MTV (P = 0.029) or TLG (P = 0.009) along with plasmacytoma types, high-risk cytogenetics, and high bone marrow plasma cell frequencies demonstrated strong predictive capabilities for the 5.3-year long-term OS. Therefore, baseline high MTV or TLG measured by PET/CT are recognized as adverse prognostic indicators for the incidence of severe CRS and poor outcomes in patients with R/R MM undergoing BCMA CAR T-cell therapy.

Academic autologous cell manufacturing offers key advantages, including cost-effectiveness, accessibility, and flexibility. However, the management of Raw Materials, Reagents, and Consumables (RMRCs) is essential for ensuring product purity, safety, and effectiveness. Variations in RMRC quality can increase production costs and result in batch failures. This work from the GMP-Bioproduction group of the French Consortium in Advancing Cancer Cell and Gene Therapy (UNITC) outlines a multicenter study conducted from 2022 to 2024 across all 11 French academic cell and gene therapy facilities producing Advanced Therapy Medicinal Products, evaluating current RMRC management practices. The study highlights significant challenges, including supply shortages, reference changes, and inconsistent quality controls. While RMRC-related non-conformities accounted for only 6.8% of total issues, they frequently required complex procedural adjustments, resulting in added financial and operational burdens. Despite differences in production scale and ATMP types, all centers consistently evaluated the criticality of RMRC, reflecting strong alignment in risk assessment practices. To address these issues, the study proposes recommendations, including a unified RMRC risk classification system, harmonized quality assurance processes. These actions aim to strengthen regulatory compliance, enhance collaboration across academic centers, and improve the overall resilience of academic decentralized CAR-T cells manufacturing in France.

Total body irradiation (TBI) plus chemotherapy is commonly applied prior to allogeneic hematopoietic stem cell transplantation (SCT) for patients with acute lymphoblastic leukemia (ALL). Here, we retrospectively analyzed registry data from the German Multicenter Study Group for Adult ALL (GMALL) and report the outcomes for 111 adult ALL patients who received 8 Gy TBI-based SCT conditioning in first complete remission between 2002 and 2018 after initial treatment with pediatric-based approaches. Patients had a median age of 52 years (range 18-65) at initial diagnosis, and the majority of patients (93%) had a good performance status (ECOG 0/1). 97 patients (87%) showed high-risk features according to GMALL criteria, of whom 58 (60%) were Philadelphia chromosome/BCR::ABL1-positive. With a median follow-up of 3.1 years after SCT, the survival rates at one, three, and five years were 72%, 64%, and 57% for disease-free survival, and 76%, 67%, and 61% for overall survival, respectively. The rates of non-relapse mortality at one, three, and five years were 22%, 26%, and 30%, while the cumulative incidences of relapse were 7%, 10%, and 14%, respectively. In summary, 8 Gy TBI conditioning in ALL patients was feasible and resulted in outcomes similar to those previously reported for 12 Gy conditioning regimens.