Late infection-related mortality in asplenic survivors of childhood cancer: A report from the childhood cancer survivor study

Brent R. Weil, Arin L. Madenci, Qi Liu, Rebecca M. Howell, Todd M. Gibson, Yutaka Yasui, Joseph P. Neglia, Wendy M. Leisenring, Susan A. Smith, Emily S. Tonorezos, Danielle N. Friedman, Louis S. Constine, Christopher L. Tinkle, Lisa R. Diller, Gregory T. Armstrong, Kevin C. Oeffinger, Christopher B. Weldon

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose Infection-related outcomes associated with asplenia or impaired splenic function in survivors of childhood cancer remains understudied. Methods Late infection-related mortality was evaluated in 20, 026 5-year survivors of childhood cancer (diagnosed < 21 years of age from 1970 to 1999; median age at diagnosis, 7.0 years [range, 0 to 20 years]; median follow-up, 26 years [range, 5 to 44 years]) using cumulative incidence and piecewise-exponential regression models to estimate adjusted relative rates (RRs). Splenic radiation was approximated using average dose (direct and/or indirect) to the left upper quadrant of the abdomen (hereafter, referred to as splenic radiation). Results Within 5 years of diagnosis, 1, 354 survivors (6.8%) had a splenectomy and 9, 442 (46%) had splenic radiation without splenectomy. With 62 deaths, the cumulative incidence of infection-related late mortality was 1.5% (95% CI, 0.7% to 2.2%) at 35 years after splenectomy and 0.6% (95% CI, 0.4% to 0.8%) after splenic radiation. Splenectomy (RR, 7.7; 95% CI, 3.1 to 19.1) was independently associated with late infection-related mortality. Splenic radiation was associated with increasing risk for late infection-related mortality in a dose-response relationship (0.1 to 9.9 Gy: RR, 2.0; 95% CI, 0.9 to 4.5; 10 to 19.9 Gy: RR, 5.5; 95% CI, 1.9 to 15.4; ≥ 20 Gy: RR, 6.0; 95% CI, 1.8 to 20.2). High-dose alkylator chemotherapy exposure was also independently associated with an increased risk of infection-related mortality (RR, 1.9; 95% CI, 1.1 to 3.4). Conclusion Splenectomy and splenic radiation significantly increase risk for late infection-related mortality. Even low-to intermediate-dose radiation exposure confers increased risk, suggesting that the spleen is highly radiosensitive. These findings should inform long-term follow-up guidelines for survivors of childhood cancer and should lead clinicians to avoid or reduce radiation exposure involving the spleen whenever possible.

Original languageEnglish (US)
Pages (from-to)1571-1578
Number of pages8
JournalJournal of Clinical Oncology
Issue number16
StatePublished - Jun 1 2018

Bibliographical note

Funding Information:
Supported by National Cancer Institute Grant No. CA55727 (G.T.A., Principal Investigator) and by Cancer Center Support (CORE) Grant No. CA21765 (C. Roberts, Principal Investigator) to St Jude Children's Research Hospital, and the American Lebanese Syrian Associated Charities.

Publisher Copyright:
© 2018 by American Society of Clinical Oncology.


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