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The outcomes of patients with acute lymphoblastic leukaemia (ALL) presenting relapse after allogeneic stem cell transplant (allo‐SCT) are poor, with few data available in this setting. Objective and Methods To evaluate the outcomes of patients with ALL presenting relapsed after allo‐SCT, we performed a retrospective study including 132 from 11 centres in Spain. Results Therapeutic strategies consisted of palliative treatment (n = 22), chemotherapy (n = 82), tyrosine kinase inhibitors (n = 26), immunotherapy with inotuzumab and/or blinatumumab (n = 19), donor lymphocyte infusions (n = 29 pts), second allo‐SCT (n = 37) and CAR T therapy (n = 14). The probability of overall survival (OS) at 1 and 5 years after relapse was 44% (95% confidence interval [CI]: 36%; 52%) and 19% (95% CI: 11%; 27%). In the 37 patients undergoing a second allo‐SCT, the 5‐year estimated OS probability was 40% [22%; 58%]. Younger age, recent allo‐SCT, late relapse, 1st complete remission at 1st allo‐SCT and chronic graft‐versus‐host disease confirmed their positive impact on survival in the multivariable analysis. Conclusion Despite the poor prognosis of patients with ALL presenting relapse after a first allo‐SCT, some can be satisfactorily rescued and a second allo‐SCT still remains a valid option for selected patients. Moreover, emerging therapies really might improve ALL patients outcome when relapsing after an allo‐SCT.

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