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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.
 Previous Article | Next Article 
Submitted September 2, 2004
Accepted December 30, 2004
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 D Rizzo, Gerard Socie, Kathleen A Sobocinski, Mary E Flowers, William D Travis, Lois B Travis, Mary M Horowitz, and H J Deeg
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
School of Public Health, University of California, Berkeley, CA, USA
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA
Hopital Saint Louis, Hematologie-Greffe de Moelle, Paris, France
Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA
Armed Forces Institute of Pathology, Washington, DC, USA
* Corresponding author; email: rcurtis{at}mail.nih.gov.
Previous studies of hematopoietic stem cell transplant (HCT) recipients suggest that graft-versus-host disease (GvHD) and its therapy may increase the risk of solid cancers, particularly squamous cell carcinomas (SCC) 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 post-transplant solid cancers (58 SCC, 125 non-SCC) and 501 matched controls within a cohort of 24,011 patients who received HCT at 215 centers worldwide. Our results showed that chronic GvHD and its therapy were strongly related to the risk of SCC, whereas no increase in risk was found for non-SCC cancers. Long duration of chronic GvHD therapy (p=0.0001), the use of azathioprine, particularly when combined with cyclosporine and steroids (p= 0.0002), and severe chronic GvHD (p=0.004) were identified as major risk factors for the development of SCC. Since 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 the use of azathioprine were also significant risk factors for SCC of the skin and of the oral mucosa. These data provide further encouragement to strategies to prevent chronic GHVD, and for those patients with moderate/severe chronic GvHD, the development of more effective and less carcinogenic treatment regimens. 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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