Few Childhood-Cancer Survivors Will Eventually Require Solid Organ Transplants

By Will Boggs MD

September 11, 2019

NEW YORK (Reuters Health) - Few childhood-cancer survivors will eventually require solid organ transplants because of severe end-organ failure, according to findings from the Childhood Cancer Survivor Study (CCSS).

"Less than 1% of survivors of childhood cancer in the Childhood Cancer Survivor Study cohort diagnosed 1970 through 1986 developed organ failure requiring waitlisting for or receiving a solid organ transplant," Dr. Amanda M. Termuhlen of the University of Minnesota Medical School, in Minneapolis, told Reuters Health by email.

More than four out of five children treated for malignancy will become long-term survivors and will face an increased risk of long-term morbidity and premature mortality from renal, cardiac, hepatic, pulmonary and other chronic medical conditions.

Dr. Termuhlen and colleagues used linked data from more than 13,000 CCSS participants to identify and describe outcomes among those survivors who subsequently underwent kidney, heart, liver, or lung transplantation.

Overall, 100 of these survivors underwent 103 solid organ transplants during follow-up. Another 67 survivors were waitlisted but never received an organ during follow-up, the team reports in The Lancet Oncology, online August 27.

At 35 years after cancer diagnosis, the cumulative incidences were 0.39% for kidney transplantation, 0.30% for heart transplantation, 0.07% for liver transplantation and 0.05% for lung transplantation.

The estimated survivals were 93.5% at five years and 73.6% at 10 years after kidney transplantation; 80.6% at five years after heart transplantation; 27.8% at five years after liver transplantation; and 34.3% at five years after lung transplantation.

Exposure to ifosfamide and receiving total body irradiation were strong risk factors for end-stage kidney disease warranting transplant. Anthracycline exposure and heart radiation dose increased the risk of end-stage heart failure warranting transplant.

Dactinomycin and methotrexate exposure were associated with end-stage liver disease warranting transplant, and exposure to carmustine and lung radiation over 10 Gy were associated with pulmonary damage severe enough to warrant lung transplant.

"Solid organ transplantation should be strongly considered in 5-year pediatric cancer survivors with severe organ damage or failure," Dr. Termuhlen said.

"The study population included children and adolescents with pediatric cancer diagnosed from 1970 through 1986," she said. "With continued long-term follow-up of pediatric cancer survivors, through studies such as the Childhood Cancer Survivor Study, a goal of pediatric cancer investigators is to modify frontline therapy for many childhood cancers to maintain or improve cure while decreasing the exposure to known risks of late complications such as those seen in this study (i.e., radiation or anthracycline exposure)."

"The future looks brighter for children and adolescents diagnosed with pediatric cancer after 1986, with hopefully less long-term organ damage needing solid organ transplantation," Dr. Termuhlen said.

Dr. Jeanette F. Winther, who heads the Childhood Cancer research group at the Danish Cancer Society in Copenhagen and co-authored an editorial accompanying the study, told Reuters Health by email, "The findings by CCSS provide new insights about organ transplantations in childhood cancer survivors - an important first step in addressing knowledge gaps within this understudied research field."

"Until we know more about the risk of subsequent cancer in childhood cancer survivors treated with immunosuppressive agents, it is important to monitor for relapse of the primary cancer or development of secondary malignancies to prevent or detect and treat cancers at an earlier stage," she said. "Organ transplants should be considered for childhood cancer survivors with life-threatening treatment-induced end-organ failure."

Dr. Smita Bhatia of the University of Alabama at Birmingham, who studies outcomes in childhood-cancer survivors and was not involved in the new work, told Reuters Health by email, "Long-term treatment-related complications can result in irreparable organ damage. The very encouraging 5-year survival after kidney and heart transplantation makes me think that these patients should be considered for organ transplants as an earlier option than is currently practiced."

SOURCE: https://bit.ly/2kug15C and https://bit.ly/2kug3KM

Lancet Oncol 2019.