儿童低二倍体或BCR::ABL1融合B前体急性淋巴细胞白血病接受异基因造血干细胞移植的结局：FORUM研究结果

Hypodiploid and BCR::ABL1+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL) confers a high risk of disease relapse. We investigated post-hematopoietic stem cell transplantation (HSCT) outcomes within the prospective FORUM trial, comparing outcomes among these genetic subgroups with those of patients without these lesions. The use of pre- and post-HSCT add-on treatments, including tyrosine kinase inhibitors (TKI) and immunotherapies, was also assessed. Multivariate analysis evaluated associations with overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR). The FORUM trial enrolled 741 patients aged ≥4 years with BCP-ALL who underwent HSCT from HLA-matched donors (2013-2023). The 3-year OS and EFS did not differ significantly between patients with BCR::ABL1 fusion, hypodiploidy, and neither of these 2 genetic lesions. However, patients with hypodiploid BCP-ALL in second complete remission (CR2) showed inferior OS and EFS, driven by higher nonrelapse mortality (NRM), which occurred exclusively in near-diploid cases. No NRM occurred in severe hypodiploid cases conditioned with total body irradiation. Minimal residual disease (MRD) positivity at transplant predicted worse OS, EFS, and CIR in all genetic groups. Patients with hypodiploid BCP-ALL were difficult to salvage after relapse, even with chimeric antigen receptor T-cell therapy. By contrast, BCR::ABL1+ patients had favorable outcomes, even when MRD positive before HSCT. Prophylactic TKI use after HSCT improved EFS and reduced CIR. BCR::ABL1+ patients who received a transplant in CR2 had a 3-year OS of 96%. In conclusion, the standardized FORUM protocol yielded comparable outcomes across genetic subgroups. Posttransplant TKI maintenance improved outcomes in BCR::ABL1+ BCP-ALL. This trial was registered at www.clinicaltrials.gov as #NCT01949129 and at www.clinicaltrialsregister.eu as #EudraCT2012-0032-22.