Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.
We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)
Krishnan
A
A
Divisions of Hematology and Bone Marrow Transplantation, Pediatric Oncology, Biostatistics and Pathology, City of Hope National Medical Center, Duarte, CA 91010-3000, USA.
Bhatia
S
S
Slovak
M L
ML
Arber
D A
DA
Niland
J C
JC
Nademanee
A
A
Fung
H
H
Bhatia
R
R
Kashyap
A
A
Molina
A
A
O'Donnell
M R
MR
Parker
P A
PA
Sniecinski
I
I
Snyder
D S
DS
Spielberger
R
R
Stein
A
A
Forman
S J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D002140:California / Q000453:epidemiology; D016022:Case-Control Studies; D015331:Cohort Studies; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D007953:Leukemia, Radiation-Induced / Q000453:epidemiology / Q000209:etiology; D008223:Lymphoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D016017:Odds Ratio; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects
D005047:Etoposide