Total body irradiation as part of conditioning regimens in childhood leukemia-long-term outcome, toxicity, and secondary malignancies

Abstract

Background: Total body irradiation (TBI) is an established part of conditioning regimens prior to stem cell transplantation in childhood leukemia but is associated with long-term toxicity. We retrospectively analyzed survival, long-term toxicity, and secondary malignancies in a pooled cohort of pediatric patients (pts.) treated with the same TBI regimen.

Methods: Analyzed were 109 pts. treated between September 1996 and November 2015. Conditioning treatment according to EBMT guidelines and the ALL SCTped 2012 FORUM trial consisted of chemotherapy (CT) and TBI with 2 Gy b.i.d. on 3 consecutive days to a total dose of 12 Gy. Median follow-up was 97.9 months (2-228 months).

Results: Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Long-term toxicity developed in 47 pts. After chronically abnormal liver and kidney parameters in 31 and 7 pts., respectively, growth retardation was the most frequent finding as seen in 13 pts. Secondary malignancies were rare (n = 3).

Conclusion: TBI-containing conditioning regimens in pediatric stem cell transplantation (SCT) are highly effective. Efforts to replace TBI- with CT-containing regimens have only been successful in subgroups of pts. Although we could show long-term toxicity in 43% of pts., overall survival was 63% at 10 years. Still, long-term effects such as growth retardation can permanently impact the pts.' quality of life and functioning. Along with new substances, efforts should be undertaken to optimize TBI techniques and accompany the treatment by systematic follow-up programs beyond 5 years to improve detection of rare events.

Keywords: Cancer of the blood; Late adverse events; Pediatric; Radiation induced cancer; Survival.

Fig. 1

Long-term toxicity. Out of the whole cohort of 109 pts., long-term toxicity was found in 47 (43%), with chronically abnormal liver function tests, growth retardation, abnormal kidney function test, and hypothyroidism being the most frequent. Secondary malignancy and cataracts were found in only 3 pts. each. Since pts. could show more than one late effect, the numbers overlap. The percentages refer to the whole cohort of 109 pts. Pts. patients

Fig. 2

Overall survival (OS) in our cohort at 2, 5, and 10 years was 86.1, 75.5, and 63.0%, respectively. Median survival was not reached. Patients treated in CR2 (2nd complete remission) showed similar OS data at 2, 5, and 10 years with 97.8, 88.0, and 65.7%, respectively