Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia

Alvaro Aguayo, Jorge Cortes, Deborah Thomas, Sherry Pierce, Michael Keating, Hagop Kantarjian

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

BACKGROUND. L-asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule-dependent fashion. A new preparation of L-asparaginase, polyethylene-glycol conjugated (PEG)- asparaginase, is a pharmacologically different formulation of L-asparaginase with distinct properties including a longer half-life and less immunogenic properties. METHODS. Patients with refractory or recurrent acute lymphoblastic leukemia (ALL) were treated with a combination of methotrexate (MTX), vincristine, PEG-asparaginase, and prednisone (MOAP). The treatment was comprised of MTX, 100 mg/m2 intravenously (i.v.), over 15 minutes on Days 1 and 14, PEG-asparaginase, 2500 IU/m2, with a maximum dose of 3750 IU i.v. approximately 4-6 hours after MTX on Days 1 and 14; vincristine, 1.4 mg/m2 (maximum dose, 2 mg) i.v., over 15 minutes on Days 1, 7, and 14; and prednisone, 200 mg daily orally, on Days 1-5 and 14-19. RESULTS. Thirty-two patients with a median age of 34 years (range, 20-74 years) were treated. Eight patients (25%) had ALL that was refractory to prior therapy and 24 patients (75%) had recurrent disease. Seven patients (22%) achieved a complete remission (CR). Five patients (16%) died early due to infections. Features associated with a poor response were high pretreatment lactate dehydrogenase levels and Philadelphia chromosome positive disease. The median duration of CR was 16 weeks and the overall median survival after MOAP therapy was 12 weeks. Anaphylactic reactions were not observed during MOAP combination therapy. CONCLUSIONS. MOAP is an active regimen in patients with refractory or recurrent ALL. This regimen is well tolerated and is not associated with allergic reactions. However, further studies regarding the pharmacologic interaction of MTX with PEG-asparaginase are needed to optimize this regimen.

Original languageEnglish (US)
Pages (from-to)1203-1209
Number of pages7
JournalCancer
Volume86
Issue number7
DOIs
StatePublished - Oct 1 1999
Externally publishedYes

Keywords

  • Acute lymphoblastic leukemia
  • L-asparaginase
  • Polyethylene-glycol conjugated (PEG)-asparaginase
  • Recurrent
  • Refractory

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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