KEY TAKEAWAYS
- The study aimed to investigate how TBI affects the risk of secondary malignancies in long-term AML survivors post-allo-HSCT.
- Researchers found an inverse relationship between TBI doses and secondary malignancies, but age and competing risks complicate the results.
Total body irradiation (TBI)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for certain patients with acute myeloid leukemia (AML). However, secondary malignancies can contribute to long-term morbidity and mortality, with TBI potentially affecting these risks.
Isabella Gruber and the team aimed to assess the impact of TBI on the development of secondary malignancies in long-term AML survivors post-allo-HSCT.
They performed an inclusive analysis of 89 consecutive patients with AML who underwent TBI-based conditioning before their first allo-HSCT between 2000 and 2016. The study examined cumulative incidences of secondary solid malignancies and precancerous lesions. TBI was administered with an average dose rate of 4 cGy/min and twice-daily fractionation. Cause-specific hazard models were employed to evaluate risk factors for secondary malignancies and precancerous lesions, while accounting for competing risks of death before the development of these conditions.
The results showed that the median patient age at TBI was 42.5 years with an interquartile range, 32.5-51.2, and a median follow-up of 15.2 years (interquartile range, 13.0-18.2). Most patients received myeloablative conditioning (MAC) with 8 Gy (n = 47) or 12 Gy TBI (n = 11), while 31 patients were treated with reduced-intensity regimens (RIC, 4 Gy TBI). Notably, patients receiving RIC were older than those receiving MAC.
The most common cancer types were non-squamous cell carcinomas (n = 14), excluding 1 patient diagnosed with sarcoma within less than a year after TBI. The cumulative incidences of secondary malignancies and precancerous lesions were 8% (95% CI, 4-16), 14% (95% CI, 7-23), and 17% (95% CI, 9-27) at 10, 15, and 20 years, respectively. In contrast, the cumulative incidences of premature deaths were 59% (95% CI, 48-69), 59% (95% CI, 48-69), and 64% (95% CI, 49-76).
Multivariate analyses revealed that higher patient age at TBI was associated with lower rates of secondary malignancies and precancerous lesions, while older age also showed a trend towards increased premature deaths before the development of malignancies. Higher TBI doses, primarily given to younger patients, were linked to lower rates of secondary malignancies and precancerous lesions without affecting mortality. Chronic GVHD requiring systemic immunosuppression was associated with premature deaths.
The study concluded that competing risks significantly influence these findings, although there is an inverse relationship between TBI doses and treatment-related malignancies. The observed age dependency reflects the lower life expectancy of older patients, independent of malignancies, highlighting the complexities introduced by competing risks.
No funding information was given.
Source: https://pubmed.ncbi.nlm.nih.gov/39289692/
Gruber I, Wolff D, Koelbl O, (2024). “Secondary solid malignancies in long-term survivors after total body irradiation.” Radiat Oncol. 2024;19(1):122. Published 2024 Sep 17. doi:10.1186/s13014-024-02520-8
