Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment.
Event-free survival for children with acute lymphoblastic leukemia (ALL) now exceeds 80% in the most effective trials. Failures are due to relapse, toxicity, and second cancers such as therapy-related myeloid leukemia or myelodysplasia (t-ML). Topoisomerase II inhibitors and alkylators can induce t-ML; additional risk factors for t-ML remain poorly defined. The occurrence of t-ML among children who had received granulocyte colony-stimulating factor (G-CSF) following ALL remission induction therapy prompted us to examine this and other putative risk factors for t-ML in 412 children treated on 2 consecutive ALL protocols from 1991 to 1998. All children received etoposide and anthracyclines, 99 of whom received G-CSF; 284 also received cyclophosphamide, 58 of whom also received cranial irradiation. There were 20 children who developed t-ML at a median of 2.3 years (range, 1.0-6.0 years), including 16 cases of acute myeloid leukemia, 3 myelodysplasia, and 1 chronic myeloid leukemia. Stratifying by protocol, the cumulative incidence functions differed (P =.017) according to the use of G-CSF and irradiation: 6-year cumulative incidence (standard error) of t-ML of 12.3% (5.3%) among the 44 children who received irradiation without G-CSF, 11.0% (3.5%) among the 85 children who received G-CSF but no irradiation, 7.1% (7.2%) among the 14 children who received irradiation plus G-CSF, and 2.7% (1.3%) among the 269 children who received neither irradiation nor G-CSF. Even when children receiving irradiation were excluded, the incidence was still higher in those receiving G-CSF (P =.019). In the setting of intensive antileukemic therapy, short-term use of G-CSF may increase the risk of t-ML.
Relling
Mary V
MV
Department of Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, TN 38105, USA. mary.relling@stjude.org
Boyett
James M
JM
Blanco
Javier G
JG
Raimondi
Susana
S
Behm
Frederick G
FG
Sandlund
John T
JT
Rivera
Gaston K
GK
Kun
Larry E
LE
Evans
William E
WE
Pui
Ching-Hon
CH
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000453:epidemiology*; D016609:Neoplasms, Second Primary / Q000139:chemically induced / Q000453:epidemiology*; D010919:Placebos; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D010919:Placebos; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide