SALVAGE allogeneic haematopoietic stem cell transplantation (allo-HSCT) delivered meaningful long-term survival in patients with relapsed/refractory (r/r) B cell acute lymphoblastic leukaemia (B-ALL) who failed to achieve complete remission or minimal residual disease (MRD) negativity following CAR-T therapy.
CAR-T Failure Leaves Few Treatment Options
Patients with r/r B-ALL who do not achieve complete remission (CR) after CAR-T therapy face a particularly poor prognosis, with limited therapeutic options available. Investigators evaluated the role of salvage allo-HSCT in 82 consecutive patients treated between 2018 and 2026 who remained in non-remission (NR) or had persistent MRD positivity following CAR-T therapy.
The cohort included 23 patients with NR disease and 59 patients who achieved CR but remained MRD-positive. More than half of patients had received at least two lines of CAR-T therapy before transplantation, highlighting the heavily pretreated nature of the population. All patients underwent myeloablative conditioning and received standard graft-versus-host disease (GVHD) prophylaxis, while selected patients received molecularly guided maintenance therapy after transplant.
Allo-HSCT Delivers Survival After CAR-T Failure
All patients achieved durable engraftment following allo-HSCT. Outcomes were significantly better among patients who entered transplantation in CR compared with those in NR. Two-year overall survival (OS) reached 66.1% in the CR group versus 36.2% in the NR group, while 2-year leukaemia-free survival (LFS) was 63.4% and 33.2%, respectively.
Relapse rates were also lower among patients transplanted in CR (30.5% versus 56.5%). Notably, despite persistent disease before transplantation, nearly one-third of NR patients achieved 2-year LFS. Among MRD-positive patients, those who were flow cytometry-negative demonstrated superior survival outcomes compared with flow cytometry-positive patients, suggesting that deeper remission status before transplant may influence efficacy.
Allo-HSCT Safety Remains Encouraging
The safety profile of allo-HSCT was considered favourable in this high-risk population. Transplant-related events accounted for nine deaths (11.0%), while grade III-IV acute GVHD occurred in 20 patients and extensive chronic GVHD developed in eight patients. Multivariate analysis identified Philadelphia chromosome-positive (Ph+) disease and the number of prior CAR-T therapy lines as factors associated with LFS. Patients with Ph+ B-ALL achieved particularly encouraging outcomes, with a 2-year LFS of 71.9%, compared with 59.2% in non-Ph+ disease.
The findings suggest that salvage allo-HSCT remains a viable and potentially curative strategy for patients with r/r B-ALL who fail CAR-T therapy. Further studies are needed to refine patient selection and optimise post-transplant management to improve long-term outcomes.
Reference
Song Y et al. Long-term outcomes of allo-HSCT for relapsed/refractory B-cell acute lymphoblastic leukemia with non-remission or minimal residual disease positivity after chimeric antigen receptor T-cell therapy. Abstract EHA-6425. EHA 2026 Congress. 11-14 June 2026.
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