Immune‐Mediated Multilineage Cytopenias in Thymoma: A Retrospective Case Series

ABSTRACT Background Thymoma is associated with diverse immune abnormalities, yet immune‐mediated multilineage cytopenias are exceedingly rare and poorly defined. Their clinical features, immunologic patterns, and treatment outcomes remain unclear. Methods We retrospectively reviewed four adult patients with histologically confirmed thymoma and immune‐mediated cytopenias affecting ≥ 2 hematopoietic lineages at a tertiary hematology center. Clinical data, bone marrow morphology, immunologic studies, T‐cell receptor (TCR) clonality, cytogenetics, next‐generation sequencing (NGS), treatments, and outcomes were collected. Responses were assessed using standardized criteria for immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). Results The four patients (aged 44–75 years) showed heterogeneous temporal patterns, with cytopenias occurring either before thymoma diagnosis or years after thymectomy. Three had trilineage cytopenia and one had bicytopenia, with combinations of AIHA, ITP, AIN, and pure red cell aplasia. Bone marrow findings ranged from normal cellularity to erythroid aplasia. Two patients demonstrated clonal TCR rearrangement consistent with T‐LGL leukemia, and NGS identified mutations including TET1, EP300, and BCORL1. All received immunosuppressive therapy. Neutrophil and platelet counts responded earlier (1–2 months), whereas erythroid recovery was slower. Despite initial responses (2 CR, 2 PR), three patients relapsed and required additional therapy. After 10–84 months of follow‐up, one patient remained in CR and three in PR. Conclusions Thymoma‐associated multilineage cytopenias are heterogeneous, frequently relapsing, and driven by complex T‐cell–mediated immune dysregulation. Comprehensive evaluation and individualized immunosuppressive therapy are essential for management.