Abstract
BACKGROUND: Acute myeloid leukemia (AML)-M2b with t(8;21)(q22;q22)/RUNX1::RUNX1T1 (AML1-ETO) is associated with a high risk of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Post-transplant lymphoproliferative disorder (PTLD), particularly involving the central nervous system (CNS), confers a poor prognosis. Although CD19 chimeric antigen receptor T-cell (CAR-T) therapy is established in B-cell malignancies, its application in acute myeloid leukemia (AML) or CNS-PTLD has rarely been reported. CASE: A 24-year-old male with AML-M2b showed persistent RUNX1::RUNX1T1 (AML1-ETO) positivity after allo-HSCT. He developed an extramedullary relapse (presacral mass) at 7 months, followed by CNS-PTLD with limb palsy at 9 months post-HSCT. The disease subsequently progressed to bone marrow relapse (RUNX1::RUNX1T1 94.42%, MRD >5%). INTERVENTION: Given the co-expression of CD19 on both the AML and PTLD cells, the patient was treated with donor-derived CD19 CAR-T cells. He experienced manageable grade 1 cytokine release syndrome (CRS) and grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). OUTCOMES: The patient achieved a complete response (CR) with negative MRD, disappearance of the fusion gene, reduction of PTLD and extramedullary lesions, and recovery of limb strength. CONCLUSION: This case demonstrates the efficacy and feasibility of CD19 CAR-T therapy for concomitant post-transplant AML-M2b relapse and CNS-PTLD, leveraging their shared CD19 expression. It provides clinical evidence that targeting a shared antigen with a single CAR-T product can effectively treat heterogeneous malignancies, offering a promising new strategy for such complex cases.