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New Malignant Diseases After Allogeneic Marrow Transplantation for Childhood Acute Leukemia

From the Service d’Hématologie, Greffe de Moelle, Hôpital Saint Louis, Paris, France; Divisions of Cancer Epidemiology and Genetics, and Cancer Biology and Diagnosis, Laboratory of Pathology, National Cancer Institute, Bethesda, MD; Fred Hutchinson Cancer Research Center, Seattle, WA; International Bone Marrow Transplant Registry, Medical College of Wisconsin, Milwaukee, WI; Children’s Hospital Medical Center, Cincinnati, OH; Carolinas Medical Center, Charlotte, NC; and Armed Forces Institute of Pathology, Washington, DC.

Address correspondence to Gérard Socié, MD, PhD, Service de Greffe de Moelle et Unité de Recherche sur la Biologie des Cellules Souches, Hôpital Saint-Louis, 1 Avenue Claude Vellefaux, 75475 Paris Cedex 10, France; email gsocie{at}chu-stlouis.fr

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia.

PATIENTS AND METHODS: We studied a cohort of 3,182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression.

RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P < .001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7.5), T-cell–depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1).

CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.

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