Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study.
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.
Metayer
Catherine
C
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Curtis
Rochelle E
RE
Vose
Julie
J
Sobocinski
Kathleen A
KA
Horowitz
Mary M
MM
Bhatia
Smita
S
Fay
Joseph W
JW
Freytes
Cesar O
CO
Goldstein
Steven C
SC
Herzig
Roger H
RH
Keating
Armand
A
Miller
Carol B
CB
Nevill
Thomas J
TJ
Pecora
Andrew L
AL
Rizzo
J Douglas
JD
Williams
Stephanie F
SF
Li
Chin-Yang
CY
Travis
Lois B
LB
Weisdorf
Daniel J
DJ
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
D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil; D011344:Procarbazine; D008466:Mechlorethamine; D014750:Vincristine; D003520:Cyclophosphamide; D011241:Prednisone