Originally published as JCO Early Release 10.1200/JCO.2005.05.158 on March 7 2005

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Increasing Incidence of Late Second Malignancies After Conditioning With Cyclophosphamide and Total-Body Irradiation and Autologous Bone Marrow Transplantation for Non-Hodgkin’s Lymphoma

From the Department of Medical Oncology, Department of Biostatistical Science, Dana-Farber Cancer Institute; Department of Medicine, Brigham and Women’s Hospital; Department of Medicine, Massachusetts General Hospital; and Department of Medicine, Harvard Medical School, Boston, MA; James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY

Address reprint requests to Arnold S. Freedman, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: arnold_freedman{at}dfci.harvard.edu

PURPOSE: Although the risk of myelodysplastic syndrome (MDS) has been well-described following autologous bone marrow transplantation (ABMT), the risk of solid tumors has been poorly characterized. We report the incidence and outcome of solid tumors at 10-year follow-up in a large cohort of uniformly treated patients who underwent ABMT for non-Hodgkin’s lymphoma (NHL).

PATIENTS AND METHODS: Between 1982 and 1997, 605 patients underwent ABMT for B-cell NHL, with uniform conditioning with cyclophosphamide and total-body irradiation followed by reinfusion of autologous bone marrow purged with anti–B-cell monoclonal antibodies. Current information on relapse of disease and second malignancies was obtained via an institutional review board–approved questionnaire sent to the referring oncologists.

RESULTS: Forty-two solid tumors, six non-MDS hematologic malignancies, 39 nonmelanoma skin cancers, and 68 cases of MDS/acute myelogenous leukemia (AML) were observed at a median follow-up of 9.5 years. A cumulative incidence model using death as a competing risk found that the 10-year incidence of second malignancy is 21%, with 10.0% non-MDS malignancies. The projected incidence of all malignancies at 15 years is 29%. The principal risk factor for second malignancy is increased age at ABMT (P = .0002). In the entire cohort, 9.6% of patients have died of second malignancy.

CONCLUSION: Lengthy follow-up demonstrates a significant incidence of second malignancies after ABMT for NHL. Although the incidence of MDS/AML starts to plateau, the incidence of solid tumors continues to rise. Second malignancies are responsible for a significant fraction of overall mortality following ABMT.

Supported in part by the Clinical Investigator Training Program (J.R.B.): Harvard/Massachusetts Institute of Technology Health Sciences and Technology—Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc.

Presented in part at the Annual Meeting of the American Society of Hematology, San Diego, CA, December 8, 2003.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

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