Background: Serious chronic medical conditions occur in childhood cancer survivors. We aimed to investigate incidence of and risk factors for end-organ damage resulting in registration on a waiting list for or receiving a solid organ transplantation and 5-year survival following these procedures. Methods: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort of individuals who survived at least 5 years after childhood cancer diagnosed at younger than 21 years of age, between Jan 1, 1970, and Dec 31, 1986, at one of 25 institutions in the USA. We linked data from CCSS participants treated in the USA diagnosed between Jan 1, 1970, and Dec 31, 1986 (without solid organ transplantation before cohort entry) to the Organ Procurement and Transplantation Network—a database of all US organ transplants. Eligible participants had been diagnosed with leukaemia, lymphoma, malignant CNS tumours, neuroblastoma, Wilms' tumours, and bone and soft tissue sarcomas. The two primary endpoints for each type of organ transplant were date of first registration of a transplant candidate on the waiting list for an organ and the date of the first transplant received. We also calculated the cumulative incidence of being placed on a waiting list or receiving a solid organ transplantation, hazard ratios (HRs) for identified risk factors, and 5-year survival following transplantation. Findings: Of 13 318 eligible survivors, 100 had 103 solid organ transplantations (50 kidney, 37 heart, nine liver, seven lung) and 67 were registered on a waiting list without receiving a transplant (21 kidney, 25 heart, 15 liver, six lung). At 35 years after cancer diagnosis, the cumulative incidence of transplantation or being on a waiting list was 0·54% (95% CI 0·40–0·67) for kidney transplantation, 0·49% (0·36–0·62) for heart, 0·19% (0·10–0·27) for liver, and 0·10% (0·04–0·16) for lung. Risk factors for kidney transplantation were unilateral nephrectomy (HR 4·2, 95% CI 2·3–7·7), ifosfamide (24·9, 7·4–83·5), total body irradiation (6·9, 2·3–21·1), and mean kidney radiation of greater than 15 Gy (>15–20 Gy, 3·6 [1·5–8·5]; >20 Gy 4·6 [1·1–19·6]); for heart transplantation, anthracycline and mean heart radiation of greater than 20 Gy (dose-dependent, both p<0·0001); for liver transplantation, dactinomycin (3·8, 1·3–11·3) and methotrexate (3·3, 1·0–10·2); for lung transplantation, carmustine (12·3, 3·1–48·9) and mean lung radiation of greater than 10 Gy (15·6, 2·6–92·7). 5-year overall survival after solid organ transplantation was 93·5% (95% CI 81·0–97·9) for kidney transplantation, 80·6% (63·6–90·3) for heart, 27·8% (4·4–59·1) for liver, and 34·3% (4·8–68·6) for lung. Interpretation: Solid organ transplantation is uncommon in ageing childhood cancer survivors. Organ-specific exposures were associated with increased solid organ transplantation incidence. Survival outcomes showed that solid organ transplantation should be considered for 5-year childhood cancer survivors with severe end-organ failure. Funding: US National Institute of Health, American Lebanese Syrian Associated Charities, US Health Resources and Services Administration.
Bibliographical noteFunding Information:
ACD and AMT designed the study. GTA and LLR provided financial support. All authors were involved in acquisition of the data. KS and WML were involved in analysis of the data. All authors were involved in interpretation of the data. ACD drafted the manuscript. All authors were involved in revising the work for important intellectual content. All authors have approved the final version of the work for publication. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
This work was supported by a grant ( U24 CA-55727 ) to GTA from the US National Institutes of Health , Bethesda, MD, Cancer Center Support (CORE) Grant (CA-21765) to St Jude Children's Research Hospital; and the American Lebanese Syrian Associated Charities, Memphis, TN. This work was also supported in part by Health Resources and Services Administration contract 234–2005–37011C . The data reported here have been in part supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network (OPTN). The content, interpretation, and reporting of these data are the responsibility of the authors alone, in no way should be seen as an official policy of, or interpretation by, the OPTN or the US Government, and do not necessarily reflect the views or policies of the US Department of Health and Human Services. Any mention of trade names, commercial products, or organisations does not imply endorsement by the US Government. No authors are employees of the US National Institutes of Health. GTA, LLR, and KCO are Principal Investigators of National Institutes of Health grants. The Childhood Cancer Survivor Study is a publicly available data resource. Investigators can apply for specific analyses through a proposal process available on the website. The dataset specific to these analyses is not publicly available.