Therapy-related myeloid neoplasms after CAR-T therapy and autologous stem cell transplantation: a systematic review of reported incidence, latency, and clonal haematopoiesis

Abstract Therapy-related myeloid neoplasms (t-MNs), including therapy-related acute myeloid leukemia and myelodysplastic syndrome, are recognized late complications of cytotoxic therapies. With the expanding use of autologous stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CAR-T) therapy, the risk, timing, and biological drivers of t-MNs in these settings remain incompletely defined. We conducted a systematic review in accordance with PRISMA 2020 guidelines. MEDLINE, Embase, CENTRAL, and grey literature sources were searched from inception to December 2025. Studies reporting t-MNs diagnosed after CAR-T therapy or ASCT with extractable data on incidence, latency, or molecular characteristics were included. Data were synthesized descriptively due to heterogeneity in study design and reporting. Reported incidence was summarized at the individual-study level, and pooled incidence estimates could not be calculated. Nine studies comprising 2,933 patients were included. A total of 195 t-MN cases were reported. Median latency varied widely, with shorter latency observed following CAR-T therapy (3-78 months). ASCT cohorts reported longer intervals (2.4-262.8 months). Clonal haematopoiesis (CH) was assessed in half of the studies, with prevalence ranging from 20% to over 80%, and higher rates among patients who developed t-MNs. Recurrent mutations in DNMT3A, TET2, and TP53 were consistently identified across both CAR-T and ASCT cohorts. Survival outcomes following t-MN diagnosis were poor, with shorter median overall survival observed in CAR-T cohorts (4.5 months) while ASCT cohorts had longer median overall survival (18.4 months). Risk of bias was moderate to high, primarily due to retrospective designs, confounding, and heterogeneity in reporting. t-MNs represent a clinically significant complication following both CAR-T therapy and ASCT, with distinct latency patterns but shared biological underpinnings driven by clonal haematopoiesis. Earlier onset and poorer survival were observed in t-MNs diagnosed after CAR-T. However, these observations should be interpreted in the context of heterogeneous study designs and prior treatment exposure. Overall, these findings highlight the need for long-term surveillance and incorporation of molecular risk stratification strategies in heavily pretreated patients.