Severe, life-threatening, and fatal chronic health conditions after allogeneic blood or marrow transplantation in childhood

Background: A comprehensive assessment of morbidity after allogeneic bone marrow transplantation (BMT) performed in childhood remains understudied. Methods: Seven hundred eighty-nine allogeneic BMT recipients who had survived ≥2 years after BMT performed between 1974 and 2014 at age <22 years and 690 siblings completed a 255-item survey self-reporting sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life-threatening], or 5 [fatal]) was assigned to the conditions using Common Terminology Criteria for Adverse Events, version 5.0. For the BMT cohort, the cumulative incidence of chronic health conditions was calculated as a function of time from BMT. Proportional subdistribution hazards models were used to determine predictors of grade 3–5 conditions. Logistic regression was used to estimate the risk of grade 3–4 conditions in BMT recipients who were alive at the time of this study compared with siblings. Results: The median age at transplantation was 11.3 years (range, 0.4–22.0 years), and the median length of follow-up was 11.7 years (range, 2.0–45.3 years). The most prevalent primary diagnoses were acute lymphoblastic leukemia (30.7%), and acute myeloid leukemia/myelodysplastic syndrome (26.9%). At age 35 years, the cumulative incidence of a grade 3–4 condition was 53.8% (95% CI, 46.7%–60.3%). The adjusted odds ratio of a grade 3–4 condition was 15.1 in survivors (95% CI, 9.5–24.0) compared with siblings. The risk of a grade 3–5 condition increased with age at BMT (hazard ratio [HR], 1.03; 95% CI, 1.01–1.05) and was higher among females (HR, 1.27; 95% CI, 1.02–1.59), patients who received total body irradiation (HR, 1.71; 95% CI, 1.27–2.31), and those reporting chronic graft-versus-host disease (HR, 1.38; 95% CI, 1.09–1.74). Conclusions: Two-year survivors of allogeneic BMT in childhood have an increased risk of grade 3–4 chronic health conditions compared with siblings, suggesting the need for long-term follow-up.