Impact of consolidative HSCT after CAR T-cell–induced remission in pediatric relapsed/refractory B-ALL: a single-center retrospective cohort

Background Whether allogeneic hematopoietic stem cell transplantation (HSCT) is required after chimeric antigen receptor T-cell (CAR-T)–induced remission in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) remains unresolved. We report single-center outcomes of CAR-T therapy with or without subsequent HSCT, evaluated using current consensus response criteria. Methods This single-center retrospective cohort study included 34 pediatric patients with R/R B-ALL who received investigational autologous CAR-T products (CD28- or 4-1BB–based; single- or dual-target) between June 2018 and December 2023. Response was assessed per National Comprehensive Cancer Network guidelines and international consensus definitions; survival by Kaplan–Meier estimation. The HSCT comparison was descriptive, complemented by a 6-month landmark analysis, a time-dependent Cox analysis restricted to patients transplanted at our center, and event-free survival (EFS) with in-remission HSCT censored at transplant. Results Median age was 7.3 years; 26 patients were relapsed and 8 refractory. CR or CRi (CR/CRi) was achieved in 26/34 (76.5%), all MRD-negative. Grade ≥3 CRS occurred in 11.8% and grade 3 ICANS in 2.9%. At a median follow-up of 21.4 months, 2-year OS and EFS were 57.4% (95% CI, 38.8–72.3) and 43.2% (26.2–59.1). Among 24 patients with marrow-involved disease achieving MRD-negative CR, 20 underwent HSCT and 4 did not; 2-year OS was 79.3% versus 25.0% (descriptive log-rank P = 0.006), and all 4 non-HSCT patients relapsed and died. In the 6-month landmark analysis (n=21), HSCT by landmark remained associated with superior OS (P = 0.047); the time-dependent Cox analysis showed a consistent association (OS: HR, 0.19 (0.04–0.90); P = 0.036). With in-remission HSCT censored, no patient remained event-free beyond 12.1 months, versus a conventional 2-year EFS of 61.8%. Two of 4 patients with isolated testicular relapse achieved durable remission without HSCT. Conclusions CAR-T therapy induced high rates of MRD-negative remission with manageable toxicity in pediatric R/R B-ALL, but rarely produced durable survival without HSCT in marrow-involved disease. Post-remission HSCT was associated with improved survival; salvage HSCT after relapse also appeared effective in a few patients. These associations are limited by the retrospective design and small sample size and require prospective confirmation.