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.