Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: A pediatric oncology group phase III trial

Donald H. Mahoney, Jonathan Shuster, Ruprecht Nitschke, Stephen J. Lauer, Naomi Winick, C. Philip Steuber, Bruce Camitta

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine whether early intensification with 12 courses of intravenous methotrexate and intravenous mercaptopurine (IVMTX/IVMP) is superior to 12 courses of repetitive, low-dose oral MTX with IV MP (LDMTX/IVMP) for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). Patients and Methods: Seven hundred nine patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction. Patients were randomized to receive intensification with either IVMTX 1,000 mg/m2 plus IVMP 1,000 mg/m2 (regimen A) or LDMTX 30 mg/m2 every 6 hours for six doses with IVMP 1,000 mg/m2 (regimen B). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy (TIT) was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and TIT every 12 weeks for 2 years. Results: Six hundred ninety-nine (99%) patients achieved remission. Three hundred forty-nine were assigned to regimen A and 350 to regimen B. The estimated 4-year continuous complete remission (CCR) rate far patients treated with regimen A is 80.3% (SE= 2.9%) and with regimen B is 75.9% (SE= 3.1%). By log-rank analysis, regimen A demonstrated superior CCR (P = .013. Transient neutropenia/thrombocytopenia, bacterial sepsis, neurotoxicity, stomatitis, and hospitalizations were more frequent among patients treated on regimen A. Conclusion: Intensification with IVMTX/IVMP is more effective than LDMTX/IVMP for prevention of relapse in children with B-precursor ALL at lower risk for relapse.

Original languageEnglish (US)
Pages (from-to)246-254
Number of pages9
JournalJournal of Clinical Oncology
Volume16
Issue number1
StatePublished - Jan 1998

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6-Mercaptopurine
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Pediatrics
Secondary Prevention
Remission Induction
Asparaginase
Stomatitis
Vincristine
Prednisone
Neutropenia
Thrombocytopenia
Sepsis
Hospitalization
Therapeutics
Recurrence
Regimen B

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia : A pediatric oncology group phase III trial. / Mahoney, Donald H.; Shuster, Jonathan; Nitschke, Ruprecht; Lauer, Stephen J.; Winick, Naomi; Steuber, C. Philip; Camitta, Bruce.

In: Journal of Clinical Oncology, Vol. 16, No. 1, 01.1998, p. 246-254.

Research output: Contribution to journalArticle

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title = "Intermediate-dose intravenous methotrexate with intravenous mercaptopurine is superior to repetitive low-dose oral methotrexate with intravenous mercaptopurine for children with lower-risk B-lineage acute lymphoblastic leukemia: A pediatric oncology group phase III trial",
abstract = "Purpose: To determine whether early intensification with 12 courses of intravenous methotrexate and intravenous mercaptopurine (IVMTX/IVMP) is superior to 12 courses of repetitive, low-dose oral MTX with IV MP (LDMTX/IVMP) for prevention of relapse in children with lower-risk B-lineage acute lymphoblastic leukemia (ALL). Patients and Methods: Seven hundred nine patients were entered onto the study. Vincristine, prednisone, and asparaginase were used for remission induction. Patients were randomized to receive intensification with either IVMTX 1,000 mg/m2 plus IVMP 1,000 mg/m2 (regimen A) or LDMTX 30 mg/m2 every 6 hours for six doses with IVMP 1,000 mg/m2 (regimen B). Twelve courses were administered at 2-week intervals. Triple intrathecal therapy (TIT) was used for CNS prophylaxis. Continuation therapy included standard oral MP, weekly MTX, and TIT every 12 weeks for 2 years. Results: Six hundred ninety-nine (99{\%}) patients achieved remission. Three hundred forty-nine were assigned to regimen A and 350 to regimen B. The estimated 4-year continuous complete remission (CCR) rate far patients treated with regimen A is 80.3{\%} (SE= 2.9{\%}) and with regimen B is 75.9{\%} (SE= 3.1{\%}). By log-rank analysis, regimen A demonstrated superior CCR (P = .013. Transient neutropenia/thrombocytopenia, bacterial sepsis, neurotoxicity, stomatitis, and hospitalizations were more frequent among patients treated on regimen A. Conclusion: Intensification with IVMTX/IVMP is more effective than LDMTX/IVMP for prevention of relapse in children with B-precursor ALL at lower risk for relapse.",
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AU - Shuster, Jonathan

AU - Nitschke, Ruprecht

AU - Lauer, Stephen J.

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AU - Steuber, C. Philip

AU - Camitta, Bruce

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