Therapy-Related Acute Lymphoblastic Leukemia with Plasmablastic Morphology after Myeloma: a Pitfall.

BACKGROUND: Therapy-related acute lymphoblastic leukemia (t-ALL) after multiple myeloma (MM) treatment is a rare complication linked to lenalidomide and autologous stem cell transplantation (ASCT). Diagnosing t-ALL vs. MM relapse is challenging when blasts show plasmablastic morphology. METHODS: An elderly male with IgA-λ MM, previously treated with double ASCT and lenalidomide, presented with fatigue and hematochezia. Pancytopenia was noted. Bone marrow showed 35.0% plasmablastic cells, raising concern for relapse. RESULTS: Flow cytometry confirmed CD34/TdT/CD19-positive B-ALL, not myeloma. Karyotype was normal; NGS revealed a DNMT3A mutation, typical of therapy-related leukemia. This supported t-B-ALL diagnosis. CONCLUSIONS: This case highlights a diagnostic pitfall where morphology misleads. Integrated lab analysis - especially flow cytometry - is essential to classify complex malignancies and guide therapy, underscoring therapy-related leukemogenesis in MM survivors.