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Impact of chronic GVHD therapy on the development of squamous-cell cancers after hematopoietic stem-cell transplantation: an international case-control study. Blood 2005 May 15;105(10):3802-11



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-20844439888   203 Citations


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.

Author List

Curtis RE, Metayer C, Rizzo JD, SociƩ G, Sobocinski KA, Flowers ME, Travis WD, Travis LB, Horowitz MM, Deeg HJ


Mary M. Horowitz MD, MS Center Director, Professor in the Medicine department at Medical College of Wisconsin
J. Douglas D. Rizzo MD, MS Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Case-Control Studies
Child, Preschool
Follow-Up Studies
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Middle Aged
Neoplasms, Squamous Cell
Risk Factors
Time Factors
jenkins-FCD Prod-409 d1e206b0be345926047b0d9c353c78a4cce4058b