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Blood, 15 April 2008, Vol. 111, No. 8, pp. 4014-4021.
Prepublished online as a Blood First Edition Paper on February 7, 2008; DOI 10.1182/blood-2007-08-106021.


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Submitted August 10, 2007
Accepted January 25, 2008

Cause-specific mortality and second cancer incidence after non-Hodgkin lymphoma: a report from the Childhood Cancer Survivor Study

Elizabeth C Bluhm*, Cecile Ronckers, Robert J Hayashi, Joseph P Neglia, Ann C Mertens, Marilyn Stovall, Anna T Meadows, Pauline A Mitby, John A Whitton, Sue Hammond, Joseph D Barker, Sarah S Donaldson, Leslie L. Robison, and Peter D Inskip

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, United States
Department of Pediatric Oncology, Emma Children's Hospital, Academic Medical Center, Amsterdam, Netherlands
Divison of Pediatric Hematology and Oncology, Washington University School of Medicine, St. Louis, MO, United States
Division of Pediatrics, University of Minnesota School of Medicine, Minneapolis, MN, United States
Aflac Cancer Center and Blood Disorders Service, Emory Children's Center, Atlanta, GA, United States
The University of Texas M.D. Anderson Cancer Center, Houston, TX, United States
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA, United States
Fred Hutchinson Cancer Research Center, Seattle, WA, United States
Department of Pathology, Ohio State University School of Medicine, Columbus, OH, United States
IMS Management Systems, Silver Spring, MD, United States
Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA, United States
Department of Epidemiology and Cancer Control, Saint Jude Children's Research Hospital, Memphis, TN, United States

* Corresponding author; email: bluhme{at}mail.nih.gov.

Second primary malignancies and premature death are a concern for patients surviving treatment for childhood lymphomas. We assessed mortality and second malignant neoplasms (SMNs) among 1,082 five-year survivors of non-Hodgkin lymphoma (NHL) in the Childhood Cancer Survivor Study, a multi-institutional North American retrospective cohort study of cancer survivors diagnosed during 1970-1986. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated using United States population rates. Relative risks for death and solid tumor SMNs were calculated based on demographic, clinical, and treatment characteristics using Poisson regression models. There were 87 observed deaths (SMR=4.2, 95% CI: 1.8, 4.1) with elevated rates of death from solid tumors, leukemia, cardiac disease, and pneumonia. Risk for death remained elevated beyond 20 years after NHL. Risk factors for death from causes other than NHL included female sex (RR=3.4) and cardiac radiation therapy (RT) exposure (RR=1.9). There were 27 solid tumor SMNs (SIR=3.9, 95%.CI: 2.6, 5.7) with 3% cumulative incidence between 5 and 20 years after NHL diagnosis. Risk factors were female sex (RR=3.1), mediastinal NHL disease (RR=5.2), and breast irradiation (RR=4.3). Survivors of childhood NHL, particularly those treated with chest RT, are at continued increased risk of early mortality and solid tumor SMNs.


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