title: Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study.
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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Metayer
authors.forename: Rochelle E
authors.initials: RE
authors.lastname: Curtis
authors.forename: Julie
authors.initials: J
authors.lastname: Vose
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sobocinski
authors.forename: Mary M
authors.initials: MM
authors.lastname: Horowitz
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Fay
authors.forename: Cesar O
authors.initials: CO
authors.lastname: Freytes
authors.forename: Steven C
authors.initials: SC
authors.lastname: Goldstein
authors.forename: Roger H
authors.initials: RH
authors.lastname: Herzig
authors.forename: Armand
authors.initials: A
authors.lastname: Keating
authors.forename: Carol B
authors.initials: CB
authors.lastname: Miller
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Nevill
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Pecora
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Rizzo
authors.forename: Stephanie F
authors.initials: SF
authors.lastname: Williams
authors.forename: Chin-Yang
authors.initials: CY
authors.lastname: Li
authors.forename: Lois B
authors.initials: LB
authors.lastname: Travis
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000453:epidemiology* / Q000209:etiology; D007953:Leukemia, Radiation-Induced / Q000453:epidemiology / Q000209:etiology; D008223:Lymphoma / Q000628:therapy*; D008297:Male; D008466:Mechlorethamine / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D011241:Prednisone / Q000008:administration & dosage; D011344:Procarbazine / Q000008:administration & dosage; D012306:Risk; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone