Faculty Collaboration Database

Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood 2003 Mar 01;101(5):2015-23

Date

10/24/2002

Pubmed ID

12393427

DOI

10.1182/blood-2002-04-1261

Scopus ID

2-s2.0-0037370887 (requires institutional sign-in at Scopus site)   180 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 > or = 50 mg/m,2 respectively; trend over dose categories, P =.04) or chlorambucil (RRs = 3.8 and 8.4 for duration < 10 months or > 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.

Author List

Metayer C, Curtis RE, Vose J, Sobocinski KA, Horowitz MM, Bhatia S, Fay JW, Freytes CO, Goldstein SC, Herzig RH, Keating A, Miller CB, Nevill TJ, Pecora AL, Rizzo JD, Williams SF, Li CY, Travis LB, Weisdorf DJ

Authors

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin
J. Douglas Rizzo MD, MS Director, Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Adolescent
Adult
Antineoplastic Agents, Alkylating
Antineoplastic Combined Chemotherapy Protocols
Bone Marrow Transplantation
Case-Control Studies
Child
Chlorambucil
Cohort Studies
Cyclophosphamide
Dose-Response Relationship, Radiation
Female
Humans
Leukemia, Myeloid
Leukemia, Radiation-Induced
Lymphoma
Male
Mechlorethamine
Middle Aged
Multivariate Analysis
Myelodysplastic Syndromes
Neoplasms, Second Primary
Peripheral Blood Stem Cell Transplantation
Prednisone
Procarbazine
Risk
Transplantation Conditioning
Transplantation, Autologous
Vincristine
Whole-Body Irradiation