Organ transplantation in childhood cancer survivors

From the Leisenring Group, Division of Public Health Sciences

With the substantial increase in survival of childhood cancer over recent decades, understanding long-term health risks for this patient population is a top priority. Previous work in the field demonstrated high prevalence of poor health outcomes later in life due to decline in function of specific organs. For example, it is estimated that pulmonary function and cardiac conditions occur in approximately 65% and 56%, respectively, of childhood cancer survivors. The anti-cancer treatments received during childhood have been implicated in such morbidity. Despite the high rates of organ-specific adverse health outcomes, the incidence of and associated risk factors for solid organ transplantation and subsequent health outcomes have not been assessed in a large cohort of childhood cancer survivors. A new study published in the journal Lancet Oncology provides answers to these questions. Dr. Wendy Leisenring and Kristy Seidel from the Public Health Sciences Division at Fred Hutch were co-authors of the study, working with a team of collaborators.

The authors first needed to link databases on childhood cancer survivors and solid organ transplantation patients. The Childhood Cancer Survivor Study (CCSS) is a large retrospective cohort of individuals who were younger than 21 years of age at diagnosis and survived cancer for at least 5 years. Dr. Leisenring directs the Statistical Center for the CCSS here at the Fred Hutch, in collaboration with the coordinating center which is located at St Jude Children’s Hospital, led by Dr. Greg Armstrong. Over 13,300 CCSS participants were included in the analyses; the median age at time of diagnosis was 6 years and the median age at follow-up was 39 years. Information on organ recipients was acquired from the Organ Procurement and Transplantation Network (OPTN) which tracks all organ transplantations and individuals on waiting lists within the United States. In linking OPTN and CCSS, the authors focused on kidney, heart, lung, and liver transplants.

Among the CCSS cohort, 103 organ transplants were identified for 100 study participants. Kidney transplants accounted for nearly half (49%), followed by heart (36%), liver (9%), and lung (7%). An additional 67 survivors were on a waiting list but did not receive an organ. Overall, the cumulative incidence for being placed on a waiting list for or receiving an organ was low, ranging from 0.54% for kidney to 0.10% for lung. Multivariable regression analyses revealed that receiving the chemotherapeutic agent ifosfamide was associated with the greatest risk for registration on a kidney transplant waiting list. Additional significant risk factors included total body irradiation, high kidney radiation doses, and unilateral nephrectomy. For heart transplants, the highest magnitude risk factors included treatment with anthracyclines or high doses of heart-focused radiation. Treatment with dactinomycin and methotrexate increased the risk for liver transplantation while treatment with carmustine or high doses of focused radiation increased the risks for lung transplantation. 

Graphical representation of overall survival of Childhood Cancer Survivor Study participants following kidney, heart, liver, or lung transplantation.
Overall survival of Childhood Cancer Survivor Study participants following kidney, heart, liver, or lung transplantation. Image provided by Dr. Wendy Leisenring

Long-term overall survival rates following transplantation differed among the four organs (see Figure). Patients who underwent kidney transplantation had the highest 5-year survival rate at 93.5% while the survival rate for heart transplant patients was 80.6%. The survival rates for liver and lung recipients were substantially lower, at 27.8% and 34.3%, respectively. When compared to 5-year survival rates of organ transplantation patients who did not have childhood cancer, the authors found that the survival rates for both kidney and heart recipients were quite similar. In contrast, the survival following liver or lung transplantation was substantially higher for patients who were not childhood cancer survivors compared to those who were.

The results from this study provide important new insight on organ transplantation incidence and associated risk factors in childhood cancer survivors. This information is essential for understanding the potential long-term health consequences associated with anti-cancer treatments commonly used for children. In addition, the high rates of overall survival following organ transplantation support the major conclusion that childhood cancer survivors with organ failure should be candidates for organ transplantation. Although the study could not determine whether organ recipients were more likely to develop secondary cancers or relapse of the primary cancer, it is possible that future studies may be able to address this question in a more recently expanded CCSS cohort.

This work was supported by the National Institutes of Health, American Lebanese Syrian Associated Charities, and US Health Resources and Services Administration.

Dietz AC, Seidel K, Leisenring WM, Mulrooney DA, Tersak JM, Glick RD, Burnweit CA, Green DM, Diller LR, Smith SA, Howell RM, Stovall M, Armstrong GT, Oeffinger KC, Robison LL, Termuhlen AM. 2019. Solid organ transplantation after treatment for childhood cancer: a retrospective cohort analysis from the Childhood Cancer Survivor Study. Lancet Oncology. doi: 10.1016/S1470-2045(19)30418-8.