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J Clin Oncol. 2018 Jun 1;36(16):1571-1578. doi: 10.1200/JCO.2017.76.1643. Epub 2018 Apr 17.

Late Infection-Related Mortality in Asplenic Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study.

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Brent R. Weil, Arin L. Madenci, and Christopher B. Weldon, Boston Children's Hospital; Brent R. Weil, Arin L. Madenci, Lisa R. Diller, and Christopher B. Weldon, Harvard Medical School; Brent R. Weil, Lisa R. Diller, and Christopher B. Weldon, Dana-Farber Cancer Institute; Arin L. Madenci, Brigham and Women's Hospital, Boston, MA; Qi Liu, University of Alberta, Edmonton, Alberta, Canada; Rebecca M. Howell and Susan A. Smith, The University of Texas MD Anderson Cancer Center, Houston, TX; Todd M. Gibson, Yutaka Yasui, Christopher L. Tinkle, and Gregory T. Armstrong, St Jude Children's Research Hospital, Memphis, TN; Joseph P. Neglia, University of Minnesota, Minneapolis, MN; Wendy M. Leisenring, Fred Hutchinson Cancer Research Center, Seattle, WA; Emily S. Tonorezos and Danielle N. Friedman, Memorial Sloan Kettering Cancer Center, New York; Louis S. Constine, University of Rochester Medical Center, Rochester, NY; and Kevin C. Oeffinger, Duke University, Durham, NC.


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.

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