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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3802-3811.
Prepublished online as a Blood First Edition Paper on February 1, 2005; DOI 10.1182/blood-2004-09-3411.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study
Rochelle E. Curtis,
Catherine Metayer,
J. Douglas Rizzo,
Gérard Socié,
Kathleen A. Sobocinski,
Mary E. D. Flowers,
William D. Travis,
Lois B. Travis,
Mary M. Horowitz, and
H. Joachim Deeg
From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD; School of Public Health, University of California, Berkeley; Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee; Fred Hutchinson Cancer Research Center, University of Washington, Seattle; Hôpital Saint Louis, Hématologie-Greffe de Moelle, Paris, France; and Armed Forces Institute of Pathology, Washington, DC.
Previous studies of recipients of hematopoietic stem-cell transplants suggest that graft-versus-host disease (GVHD) and its therapy may increase the risk for solid cancers, particularly squamous-cell carcinomas (SCCs) of the buccal cavity and skin. However, the importance and magnitude of these associations are not well characterized. We conducted a case–control study of 183 patients with posttransplantation solid cancers (58 SCCs, 125 non-SCCs) and 501 matched control patients within a cohort of 24 011 patients who underwent hematopoietic stem-cell transplantation (HSCT) at 215 centers worldwide. Our results showed that chronic GVHD and its therapy were strongly related to the risk for SCC, whereas no increase in risk was found for non-SCCs. Major risk factors for the development of SCC were long duration of chronic GVHD therapy (P < .001); use of azathioprine, particularly when combined with cyclosporine and steroids (P < .001); and severe chronic GVHD (P = .004). Given that most patients who received prolonged immunosuppressive therapy and those with severe chronic GVHD were also treated with azathioprine, the independent effects of these factors could not be evaluated. Additional analyses determined that prolonged immunosuppressive therapy and azathioprine use were also significant risk factors for SCC of the skin and of the oral mucosa. These data provide further encouragement for strategies to prevent chronic GVHD and for the development of more effective and less carcinogenic treatment regimens for patients with moderate or severe chronic GVHD. Our results also suggest that clinical screening for SCC is appropriate among patients exposed to persistent chronic GVHD, prolonged immunosuppressive therapy, or both.
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