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Sequential administration of methotrexate and asparaginase in relapsed or refractory pediatric acute myeloid leukemia

Authors

  • Jassada Buaboonnam MD,

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, Siriraj Hospital, Mahidol University, Bangkok, Thailand
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  • Xueyuan Cao PhD,

    1. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Jennifer L. Pauley Pharm D,

    1. Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee
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  • Ching-Hon Pui MD,

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Raul C. Ribeiro MD,

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Jeffrey E. Rubnitz MD, PhD,

    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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  • Hiroto Inaba MD, PhD

    Corresponding author
    1. Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee
    2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
    • Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Mail Stop 260, Memphis, TN 38105-3678.
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  • Conflict of interest: Nothing to declare.

Abstract

Background

The efficacy of combination chemotherapy with methotrexate (MTX) and asparaginase is not well known in relapsed and refractory acute leukemia after contemporary therapy.

Procedure

A retrospective study of pediatric patients with relapsed or refractory acute myeloid leukemia (AML) who received MTX and asparaginase as a salvage therapy at St. Jude Children Research Hospital was performed. MTX was given intravenously followed by a dose of asparaginase intramuscularly or intravenously 24 hours later. The chemotherapy cycle was repeated every 7–10 days. Response, survival, and toxicities were evaluated.

Results

Fifteen patients, median age 10.5 years (range, 1.1–18.5 years), were treated. Median number of previous therapeutic regimens was three (range, 1–4). Six patients responded to treatment (three had morphologic complete remission with incomplete blood count recovery, two had partial remission, and one had stable disease for 16 months), and four are still alive. Three of six responders had monoblastic leukemia, and also developed tumor lysis syndrome. The 1- and 2-year overall survival rates are 35.6% and 17.8%, respectively. The most common adverse event was transient elevation of transaminases (nine patients). Two patients developed pancreatitis. Episodes of febrile neutropenia were rare (two patients), and most courses (75 out of 93 total courses) were given in an outpatient setting.

Conclusions

Combination chemotherapy with MTX and asparaginase appears to be an effective salvage therapy and well tolerated in patients with relapsed or refractory childhood AML, even in those heavily pretreated with contemporary frontline or salvage therapy. Pediatr Blood Cancer 2013; 60: 1161–1164. © 2013 Wiley Periodicals, Inc.

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