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 Armstrong, Kevin C. Oeffinger, Christopher B. Weldon

Research output: Contribution to journalArticle

Abstract

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
Volume36
Issue number16
DOIs
StatePublished - Jun 1 2018

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Survivors
Splenectomy
Radiation
Mortality
Infection
Neoplasms
Spleen
Alkylating Agents
Incidence
Abdomen
Guidelines
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Late infection-related mortality in asplenic survivors of childhood cancer : A report from the childhood cancer survivor study. / Weil, Brent R.; Madenci, Arin L.; Liu, Qi; Howell, Rebecca M.; Gibson, Todd M.; Yasui, Yutaka; Neglia, Joseph P.; Leisenring, Wendy M.; Smith, Susan A.; Tonorezos, Emily S.; Friedman, Danielle N.; Constine, Louis S.; Tinkle, Christopher L.; Diller, Lisa R.; Armstrong, Gregory; Oeffinger, Kevin C.; Weldon, Christopher B.

In: Journal of Clinical Oncology, Vol. 36, No. 16, 01.06.2018, p. 1571-1578.

Research output: Contribution to journalArticle

Weil, BR, Madenci, AL, Liu, Q, Howell, RM, Gibson, TM, Yasui, Y, Neglia, JP, Leisenring, WM, Smith, SA, Tonorezos, ES, Friedman, DN, Constine, LS, Tinkle, CL, Diller, LR, Armstrong, G, Oeffinger, KC & Weldon, CB 2018, 'Late infection-related mortality in asplenic survivors of childhood cancer: A report from the childhood cancer survivor study', Journal of Clinical Oncology, vol. 36, no. 16, pp. 1571-1578. https://doi.org/10.1200/JCO.2017.76.1643
Weil, Brent R. ; Madenci, Arin L. ; Liu, Qi ; Howell, Rebecca M. ; Gibson, Todd M. ; Yasui, Yutaka ; Neglia, Joseph P. ; Leisenring, Wendy M. ; Smith, Susan A. ; Tonorezos, Emily S. ; Friedman, Danielle N. ; Constine, Louis S. ; Tinkle, Christopher L. ; Diller, Lisa R. ; Armstrong, Gregory ; Oeffinger, Kevin C. ; Weldon, Christopher B. / Late infection-related mortality in asplenic survivors of childhood cancer : A report from the childhood cancer survivor study. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 16. pp. 1571-1578.
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title = "Late infection-related mortality in asplenic survivors of childhood cancer: A report from the childhood cancer survivor study",
abstract = "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.",
author = "Weil, {Brent R.} and Madenci, {Arin L.} and Qi Liu and Howell, {Rebecca M.} and Gibson, {Todd M.} and Yutaka Yasui and Neglia, {Joseph P.} and Leisenring, {Wendy M.} and Smith, {Susan A.} and Tonorezos, {Emily S.} and Friedman, {Danielle N.} and Constine, {Louis S.} and Tinkle, {Christopher L.} and Diller, {Lisa R.} and Gregory Armstrong and Oeffinger, {Kevin C.} and Weldon, {Christopher B.}",
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TY - JOUR

T1 - Late infection-related mortality in asplenic survivors of childhood cancer

T2 - A report from the childhood cancer survivor study

AU - Weil, Brent R.

AU - Madenci, Arin L.

AU - Liu, Qi

AU - Howell, Rebecca M.

AU - Gibson, Todd M.

AU - Yasui, Yutaka

AU - Neglia, Joseph P.

AU - Leisenring, Wendy M.

AU - Smith, Susan A.

AU - Tonorezos, Emily S.

AU - Friedman, Danielle N.

AU - Constine, Louis S.

AU - Tinkle, Christopher L.

AU - Diller, Lisa R.

AU - Armstrong, Gregory

AU - Oeffinger, Kevin C.

AU - Weldon, Christopher B.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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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