Premium
Repetitive low dose oral methotrexate and intravenous mercaptopurine treatment for patients with lower risk B—lineage acute lymphoblastic leukemia. A pediatric oncology group pilot study
Author(s) -
Mahoney Donald H.,
Camitta Bruce M.,
Leventhal Brigid G.,
Shuster Jonathan J.,
Civin Curt J.,
Ganick Dorothy J.,
Lauer Stephen J.,
Steuber C. Philip,
Kamen Barton A.
Publication year - 1995
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19950515)75:10<2623::aid-cncr2820751033>3.0.co;2-y
Subject(s) - medicine , mercaptopurine , methotrexate , lymphoblastic leukemia , acute lymphocytic leukemia , pediatric oncology , oncology , leukemia , lineage (genetic) , chemotherapy , cancer , biochemistry , chemistry , gene
Background . This trial evaluated the toxicity and preliminary efficacy of a repeated oral low dose (LD) methotrexate schedule with intravenous mercaptopurine infusions as intensification therapy for children with lower risk B‐lineage acute lymphoblastic leukemia (ALL). Patients and Methods . From December 1986 to January 1991, 96 children with newly diagnosed, lower risk ALL were enrolled. Vincristine, L‐asparaginase, and prednisone were used for remission induction. Age‐based methotrexate was administered intrathecally (IT) for central nervous system (CNS) prophylaxis. An outpatient‐based intensification treatment included LD methotrexate 30 mg/M 2 every 6 hours for 5 doses, followed by intravenous mercaptopurine 1000 mg/M 2 for 6 hours every 2 weeks for 12 courses. Leucovorin rescue was administered 48 hours after methotrexate treatment was begun. Maintenance therapy included standard daily oral mercaptopurine, weekly intramuscular methotrexate, and IT methotrexate every 12 weeks, for 2 years. Results . All patients had disease remission. Thirty‐two patients relapsed; there were 17 isolated bone marrow relapses, 10 isolated CNS relapses, 2 isolated testicular relapses, 1 marrow plus CNS relapse, 1 marrow plus testicular relapse, and 1 CNS plus testicular relapse. Event free survival (EFS) at 4 years was 66% (standard error, 7%) by Kaplan‐Meier analysis. Complications associated with LD methotrexate/mercaptopurine courses were few and resulted in hospital readmissions in 2.4% of courses. Two patients were unable to comply with the oral LD methotrexate schedule and intravenous methotrexate. Three patients were unable to complete scheduled maintenance because of hepatic or hematopoietic dysfunction. Conclusions . Low dose methotrexate/mercaptourine can be administered safely on an outpatient basis to children with lower risk B‐lineage ALL. However, there was a higher than expected incidence of bone marrow and CNS relapse. The reasons for this outcome were not completely clear but raise the possibility that LD methotrexate therapy may be less effective in preventing relapse than are higher dose, parenteral methotrexate regimens.