Therapy-related myelodysplastic syndrome rapidly evolving to acute myeloid leukemia following CAR-T cell therapy in a patient with refractory diffuse large B-cell lymphoma: a case report
Background Persistent cytopenia following chimeric antigen receptor T-cell (CAR-T) therapy is an increasingly recognized complication in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). While most cases stem from transient, immune-mediated mechanisms or depleted bone marrow reserves, secondary therapy-related myeloid neoplasms (t-MN) must be strongly suspected in patients presenting with prolonged, transfusion-refractory cytopenias. Case presentation We report the case of a 76-year-old woman diagnosed with refractory DLBCL (non-germinal center B-cell subtype, stage IIIA, International Prognostic Index score of 4). Following multiple lines of chemo-immunotherapy (R-CDOP, R-CDOPE, R-ICE, local radiotherapy, and one cycle of Pola-R-ICE) and subsequent autologous CAR-T cell infusion, the patient developed persistent pancytopenia, characterized by severe, transfusion-refractory thrombocytopenia. A comprehensive bone marrow evaluation performed in February 2026 revealed multilineage dysplasia, 13% blasts, TP53 deletion/mutation, and a complex karyotype, establishing a diagnosis of therapy-related myelodysplastic syndrome with low blasts (t-MDS-LB). Within two months, the disease rapidly progressed to acute myeloid leukemia (t-AML) with 35% abnormal myeloid blasts. Combination therapy with azacitidine and venetoclax was initiated but discontinued due to profound myelosuppression and severe infection. Conclusion This case underscores that persistent post-CAR-T cytopenia can serve as an early manifestation of an underlying t-MN rather than transient hematotoxicity. Prompt and comprehensive bone marrow assessments—incorporating morphology, flow cytometry, cytogenetics, and molecular profiling—are paramount for patients with extensive prior exposure to cytotoxic regimens to avoid catastrophic diagnostic delays.