A pilot study of intermediate-dose methotrexate and cytosine arabinoside, "spread-out" or "up-front," in continuation therapy for childhood non-T, non-B acute lymphoblastic leukemia. A Pediatric Oncology Group study.
One hundred six children with newly diagnosed non-T-, non-B-cell acute lymphoblastic leukemia (ALL) were treated in a Pediatric Oncology Group (POG) pilot study in which six courses of intermediate-dose methotrexate (MTX) and cytosine arabinoside (Ara-C) (1 g/m2 each) were added to a "backbone" of standard continuation therapy. The dose and sequence of MTX/Ara-C administration were based on a preclinical model that demonstrated synergism between MTX and Ara-C. Poor-risk patients (n = 49) were assigned to "up-front" therapy, in which the MTX/Ara-C courses were administered during the initial 15 weeks of remission. Standard-risk patients (n = 57) were assigned to "spread-out" therapy, in which the MTX/Ara-C courses were interspersed at 12-week intervals within continuation treatment. Toxicity after intermediate-dose MTX/Ara-C, principally neutropenia and fever, was judged significant but manageable. Unexpectedly, the incidence of fever and neutropenia less than 500/mm3 was greater after "spread-out" therapy (38%) than after "up-front" therapy (6%). At 4 years, the Kaplan-Meier estimate of event-free survival (EFS) is 71% (+/- 7%) for standard-risk patients and 53% (+/- 8%) for poor-risk patients. The results of this pilot study support the use of intermediate-dose MTX/Ara-C in additional studies.
Krance
R A
RA
Division of Pediatrics, City of Hope National Medical Center, Duarte, California.
Newman
E M
EM
Ravindranath
Y
Y
Harris
M B
MB
Brecher
M
M
Wimmer
R
R
Shuster
J J
JJ
Land
V J
VJ
Pullen
J
J
Crist
W
W
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D007223:Infant; D007239:Infections / Q000209:etiology; D007902:Length of Stay; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009503:Neutropenia / Q000139:chemically induced; D010865:Pilot Projects; D010976:Platelet Count / Q000187:drug effects; D011014:Pneumonia / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate
D003561:Cytarabine; D008727:Methotrexate