Originally published as JCO Early Release 10.1200/JCO.2005.04.2200 on March 6 2006

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Risk of Second Malignancy After Non-Hodgkin's Lymphoma: A British Cohort Study

Nadejda Y. Mudie, Anthony J. Swerdlow, Craig D. Higgins, Paul Smith, Zongkai Qiao, Barry W. Hancock, Peter J. Hoskin, David C. Linch

From the Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey; British National Lymphoma Investigation, Cancer Trials Centre, London; Department of Haematology, University College London Medical School, London; Academic Unit of Clinical Oncology, Cancer Research Centre, Weston Park Hospital, Sheffield; Clinical Oncology, Mount Vernon Hospital, Northwood, Middlesex, United Kingdom

Address reprint requests to N.Y. Mudie, MD, PhD, Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, United Kingdom; e-mail: nadejda.mudie{at}icr.ac.uk

PURPOSE: To assess long-term site-specific risks of second malignancy following non-Hodgkin's lymphoma (NHL) in relation to treatment and demographic factors.

PATIENTS AND METHODS: A cohort of 2,456 patients with NHL who were first treated from 1973 to 2000 and were younger than 60 years from centers in the British National Lymphoma Investigation were observed, and occurrences of second malignancy was compared with expectations based on general population cancer rates in England and Wales.

RESULTS: In total, 123 second malignancies occurred. Relative risks (RRs) were significantly elevated for all malignancies combined (RR = 1.3; 95% CI, 1.1 to 1.6) and for leukemia (RR = 8.8; 95% CI, 5.1 to 14.1) and lung cancer (RR = 1.6; 95% CI, 1.1 to 2.3). RRs of malignancy overall diminished significantly with increasing age at first treatment. Leukemia risk was significantly increased after chemotherapy (RR = 10.5; 95% CI, 5.0 to 19.3) and mixed-modality treatment (RR = 13.0; 95% CI, 5.2 to 26.7). Relative risks of lung (RR = 1.9; 95% CI, 1.1 to 3.1) and colorectal (RR = 2.1; 95% CI, 1.1 to 3.6) cancers were significantly raised following chemotherapy.

CONCLUSION: NHL patients are at elevated risk of developing second malignancy, particularly leukemia and lung cancer. The relative risk is greater with patients who are younger at first treatment. Chemotherapy predisposes patients toan increased risk of leukemia, and possibly lung and colorectal cancers. The role of specific drug treatments in the etiology of solid cancers after NHL deserves further investigation.

Supported by The Lymphoma Research Trust.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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