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Fludarabine, cytarabine, granulocyte colony-stimulating factor and melphalan (FALG with L-PAM) as a reduced toxicity conditioning regimen in children with acute leukemia

Authors

  • Koji Kato MD, PhD,

    Corresponding author
    1. Department of Pediatric Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
    • Correspondence to: Koji Kato, Department of Pediatric Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, 3-35 Michishita-cho, Nakamura-ku, Nagoya 453-8511, Japan.

      E-mail: kokato@nagoya-1st.jrc.or.jp

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  • Nao Yoshida MD, PhD,

    1. Department of Pediatric Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
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  • Kimikazu Matsumoto MD, PhD,

    1. Department of Pediatric Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
    Current affiliation:
    1. Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
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  • Takaharu Matsuyama MD, PhD

    1. Department of Pediatric Hematology and Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
    Current affiliation:
    1. Nagoya Nishi Hospital, Nagoya, Japan
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  • Conflict of interest: Nothing to declare.

Abstract

Background

The conventional conditioning regimen for patients with leukemia prior to allogeneic stem cell transplantation is myeloablation to eradicate residual leukemic cells and host immunocompetent cells. This helps prevent leukemic relapse as well as rejection after transplantation. A myeloablative conditioning regimen with busulfan (BU) or total body irradiation (TBI) is effective for eradication of leukemic cells but is also associated with significant toxicities in the acute or late phase in pediatric patients. In an effort to minimize these adverse effects, we conducted bone marrow transplantation (BMT) from unrelated volunteer donors using a conditioning regimen without BU or TBI.

Procedure

Ten patients with acute leukemia in first or second remission were given a “non-BU, non-TBI conditioning regimen,” which consisted of fludarabine (FLU), cytarabine (CA), and melphalan (L-PAM) after FLAG combined with L-PAM.

Results

Engraftment was obtained in all patients, and two patients died of relapse. Eight of 10 patients have been disease-free for a median of 126 months (116–142) after transplantation. The overall survival, event-free survival, relapse rate, and treatment-related mortality were 80.0%, 80.0%, 20.0% and 0.0%, respectively. In female patients, spontaneous menstruation with normal luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) levels was observed in all four patients at post-pubertal age.

Conclusions

This conditioning regimen of FLAG combined with L-PAM (which did not contain BU and TBI) was associated with good outcomes and minimal late adverse effects in children with acute leukemia who have undergone allogeneic BMT from unrelated volunteer donors. Pediatr Blood Cancer 2014;61:712–716. © 2013 Wiley Periodicals, Inc.

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