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Dear Editor,
I read with interest the Brief Article by Ladbury et al., “Risk of Subsequent Malignant Neoplasms Following Hematopoietic Stem Cell Transplantation with Total Body Irradiation or Total Marrow Irradiation: Insights from Early Follow-Up” (Transplantation and Cellular Therapy, 2022) [1]. The authors address a clinically important survivorship question, as total marrow irradiation (TMI) is increasingly used as an alternative to conventional total body irradiation (TBI) with the goals of organ sparing and, in selected settings, dose escalation [2]. The matched-pair analysis provides useful early reassurance that TMI-based conditioning was not associated with a statistically significant difference in subsequent malignant neoplasm (SMN) risk compared with TBI-based conditioning during the reported followup period, despite higher median radiation doses in the TMI cohort. The effort to enhance SMN ascertainment through an institutional long-term followup protocol and linkage with cancer registry data is also a notable strength.
At the same time, the findings should be interpreted within the context of followup duration and competing risks. The median follow-up of approximately two years is necessarily limited for evaluating radiation-associated solid SMNs, which often have latency periods extending beyond 5–10 years [3]. In addition, the TMI cohort included a substantially higher proportion of patients transplanted with induction failure or relapsed disease and experienced lower overall survival, thereby reducing the number of longterm survivors at risk for late events.
This imbalance may attenuate observable between-group differences in late SMN incidence, particularly for solid tumors expected to accumulate over time.
25 Finally, the predominance of nonmelanoma skin cancers and noninvasive lesions among reported SMNs underscores the multifactorial nature of post-transplant malignancy risk. Chronic graft-versus-host disease, prolonged immunosuppression, and prior systemic therapies are wellestablished contributors to secondary cancer risk following allogeneic transplantation and may complicate attribution of SMN risk specifically to radiation modality or dose distribution [4].
Overall, this study represents a valuable contribution to an area where evidence remains limited. Longer follow-up in larger cohorts—ideally including more standard-risk populations and
incorporating competing-risk methodology—will be essential to more definitively characterize the comparative long-term SMN risk of TMI versus TBI and to guide patient counseling. Sincerely,