Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: A multicenter case-control study

Catherine Metayer, Rochelle E. Curtis, Julie Vose, Kathleen A. Sobocinski, Mary M. Horowitz, Smita Bhatia, Joseph W. Fay, Cesar O. Freytes, Steven C. Goldstein, Roger H. Herzig, Armand Keating, Carol B. Miller, Thomas J. Nevill, Andrew L. Pecora, Douglas J. Rizzo, Stephanie F. Williams, Chin Yang Li, Lois B. Travis, Daniel J. Weisdorf

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Although numerous reports indicate that patients receiving autotransplants for lymphoma are at increased risk for myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), the separate contributions of pretransplantation- and transplantation-related therapy are not well characterized. We conducted a case-control study of 56 patients with MDS/AML and 168 matched controls within a cohort of 2 739 patients receiving autotransplants for Hodgkin disease or non-Hodgkin lymphoma at 12 institutions (1989-1995). Detailed abstraction of medical records was undertaken to determine all pre- and posttransplantation therapy, and transplantation-related procedures. In multivariate analyses, risks of MDS/AML significantly increased with the intensity of pretransplantation chemotherapy with mechlorethamine (relative risks [RRs] = 2.0 and 4.3 for cumulative doses < 50 mg/m2 and ≥ 50 mg/m,2 respectively; trend over dose categories, P = .04) or chlorambucil (RRs = 3.8 and 8.4 for duration < 10 months or ≥ 10 months, respectively; trend, P = .009), compared with cyclophosphamide-based therapy. Transplantation-conditioning regimens including total-body irradiation (TBI) at doses 12 Gy or less did not appear to elevate leukemia risk (RR = 1.3; P = .48) compared with non-TBI regimens; however, a statistically significant increased risk was found for TBI doses of 13.2 Gy (RR = 4.6; P = .03). Peripheral blood stem cells were associated with a nonsignificant increased risk of MDS/AML (RR = 1.8; P = .12) compared with bone marrow grafts. Our data show that type and intensity of pretransplantation chemotherapy with alkylating agents are important risk factors of MDS/AML following autotransplantation. Transplantation-related factors may also modulate this risk; however, the apparent contribution of high-dose TBI requires confirmation.

Original languageEnglish (US)
Pages (from-to)2015-2023
Number of pages9
JournalBlood
Volume101
Issue number5
DOIs
StatePublished - Mar 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Metayer, C., Curtis, R. E., Vose, J., Sobocinski, K. A., Horowitz, M. M., Bhatia, S., Fay, J. W., Freytes, C. O., Goldstein, S. C., Herzig, R. H., Keating, A., Miller, C. B., Nevill, T. J., Pecora, A. L., Rizzo, D. J., Williams, S. F., Li, C. Y., Travis, L. B., & Weisdorf, D. J. (2003). Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: A multicenter case-control study. Blood, 101(5), 2015-2023. https://doi.org/10.1182/blood-2002-04-1261