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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-04-1261.
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Blood, 1 March 2003, Vol. 101, No. 5, pp. 2015-2023
TRANSPLANTATION
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,
J. Douglas Rizzo,
Stephanie F. Williams,
Chin-Yang Li,
Lois B. Travis, and
Daniel J. Weisdorf
From the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, Bethesda, MD; University of
Nebraska Medical Center, Omaha, NE; Autologous Blood and Bone Marrow
Transplant Registry, Medical College of Wisconsin, Milwaukee, WI; City
of Hope National Medical Center, Duarte, CA; Baylor University Medical
Center, Dallas, TX; University of Texas, Health Science Center at San
Antonio, San Antonio, TX; H. Lee Moffitt Cancer Center, Tampa, FL;
University of Louisville Hospital, Louisville, KY; the Princess
Margaret Hospital/Ontario Cancer Institute, Toronto, ON,
Canada; Johns Hopkins Oncology Center, Baltimore, MD;
British Columbia Cancer Agency and Vancouver General Hospital,
Vancouver, BC, Canada; the Cancer Center at Hackensack
University Medical Center, Hackensack, NJ; University of Chicago
Medical Center, Chicago, IL; Mayo Clinic, Rochester, MN; and University
of Minnesota Medical School, Minneapolis, MN.
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.
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