Faculty Collaboration Database

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. Cancer 1995 May 15;75(10):2623-31

Date

05/15/1995

Pubmed ID

7736409

DOI

10.1002/1097-0142(19950515)75:10<2623::aid-cncr2820751033>3.0.co;2-y

Scopus ID

2-s2.0-0029000499 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

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/M2 every 6 hours for 5 doses, followed by intravenous mercaptopurine 1000 mg/M2 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 received intravenous methotrexate. Three patients were unable to complete scheduled maintenance because of hepatic or hematopoietic dysfunction.

CONCLUSIONS: Low dose methotrexate/mercaptopurine 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.

Author List

Mahoney DH Jr, Camitta BM, Leventhal BG, Shuster JJ, Civin CJ, Ganick DJ, Lauer SJ, Steuber CP, Kamen BA

Author

Bruce m. Camitta Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Antineoplastic Combined Chemotherapy Protocols
Asparaginase
B-Lymphocytes
Central Nervous System Neoplasms
Child
Disease-Free Survival
Female
Humans
Infusions, Intravenous
Injections, Intramuscular
Injections, Spinal
Male
Mercaptopurine
Methotrexate
Pilot Projects
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prednisone
Remission Induction
Treatment Outcome
Vincristine