Intermediate-dose methotrexate and intravenous 6-mercaptopurine chemotherapy for children with acute lymphoblastic leukemia who did not respond to initial induction therapy.
OBJECTIVE
To determine the complete remission rate of children with acute lymphoblastic leukemia (ALL) who were not induced into remission by initial therapy, when subsequently treated with intermediate-dose methotrexate and intravenous 6-mercaptopurine.


METHODS
Children with B-precursor ALL who did not achieve initial remission after 4 or 6 weeks of standard three- or four-drug induction chemotherapy were entered on study. Therapy consisted of three doses at weekly intervals of methotrexate 1,000 mg/m2 over 24 hours followed by 6-mercaptopurine 1,000 mg/m2 over 8 hours 20 minutes. Patients achieving a partial remission could receive two additional weekly courses of methotrexate and 6-mercaptopurine. Initially, patients received weekly intrathecal chemotherapy, but the study was amended to include intrathecal therapy only at week 1.


RESULTS
Nineteen patients were entered on study. All were evaluable for toxicity and response. There were seven complete remissions, four partial remissions, six patients with no response, and two children with progressive disease, for an overall complete remission rate of 37%. One patient was removed from the study after the second course of methotrexate and 6-mercaptopurine because of renal failure. Two patients had neurologic toxicity resulting in a study amendment. No patients subsequently experienced neurologic toxicity.


CONCLUSIONS
Intermediate-dose intravenous methotrexate and intravenous 6-mercaptopurine can induce remission in some patients with ALL who experience initial induction failure. Features predicting complete remission, however, could not be identified.
Ogden
Angela K
AK
Pharmacia Corporation, Peapack, New Jersey, USA.
Pollock
Brad H
BH
Bernstein
Mark L
ML
Camitta
Bruce
B
Buchanan
George R
GR
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D009325:Nausea / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012074:Remission Induction; D017211:Treatment Failure
D015122:Mercaptopurine; D002955:Leucovorin; D008727:Methotrexate