Rochelle E. Curtis, M.A., Philip A. Rowlings, M.B., B.S., H. Joachim Deeg, M.D., Donna A. Shriner, Pharm.D., Gérard Socié, M.D., Ph.D., Lois B. Travis, M.D., Mary M. Horowitz, M.D., Robert P. Witherspoon, M.D., Robert N. Hoover, M.D., Kathleen A. Sobocinski, M.S., Joseph F. Fraumeni, M.D., John D. Boice, Sc.D., H. Gary Schoch, B.A., George E. Sale, M.D., Rainer Storb, M.D., William D. Travis, M.D., Hans-Jochem Kolb, M.D., Robert Peter Gale, M.D., Ph.D., and Jakob R. Passweg, M.D.
Background The late effects of bone marrow transplantation,including cancer, need to be determined in a large populationat risk.
Methods We studied 19,229 patients who received allogeneic transplants(97.2 percent) or syngeneic transplants (2.8 percent) between1964 and 1992 at 235 centers to evaluate the risk of the developmentof a new solid cancer. Risk factors relating to the patient,the transplant, and the course after transplantation were evaluated.
Results The transplant recipients were at significantly higherrisk of new solid cancers than the general population (observedcases, 80; ratio of observed to expected cases, 2.7; P<0.001).The risk was 8.3 times as high as expected among those who survived10 or more years after transplantation. The cumulative incidencerate was 2.2 percent (95 percent confidence interval, 1.5 to3.0 percent) at 10 years and 6.7 percent (95 percent confidenceinterval, 3.7 to 9.6 percent) at 15 years. The risk was significantlyelevated (P<0.05) for malignant melanoma (ratio of observedto expected cases, 5.0) and cancers of the buccal cavity (11.1),liver (7.5), brain or other parts of the central nervous system(7.6), thyroid (6.6), bone (13.4), and connective tissue (8.0).The risk was higher for recipients who were younger at the timeof transplantation than for those who were older (P for trend,<0.001). In multivariate analyses, higher doses of total-bodyirradiation were associated with a higher risk of solid cancers.Chronic graft-versus-host disease and male sex were stronglylinked with an excess risk of squamous-cell cancers of the buccalcavity and skin.
Conclusions Patients undergoing bone marrow transplantationhave an increased risk of new solid cancers later in life. Thetrend toward an increased risk over time after transplantationand the greater risk among younger patients indicate the needfor lifelong surveillance.
Source Information
From the Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Md. (R.E.C., D.A.S., L.B.T., R.N.H., J.F.F., J.D.B.); the International Bone Marrow Transplant Registry, Medical College of Wisconsin, Milwaukee (P.A.R., M.M.H., K.A.S.); the Fred Hutchinson Cancer Research Center, Seattle (H.J.D., R.P.W.); and Hôpital Saint Louis, Hématologie–Greffe de Moelle, Paris (G.S.). Other authors were H. Gary Schoch, B.A., George E. Sale, M.D., and Rainer Storb, M.D. (Fred Hutchinson Cancer Research Center, Seattle); William D. Travis, M.D. (Armed Forces Institute of Pathology, Washington, D.C.); Hans-Jochem Kolb, M.D. (University of Munich, Munich, Germany); Robert Peter Gale, M.D., Ph.D. (Salick Health Care, Los Angeles); and Jakob R. Passweg, M.D. (International Bone Marrow Transplant Registry, Milwaukee).
Address reprint requests to Ms. Curtis at Executive Plaza North, Suite 408, National Cancer Institute, Bethesda, MD 20892.
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