Research Article

Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: A report from the Japan infant leukemia study group

  1. Daisuke Tomizawa MD1,*,
  2. Katsuyoshi Koh MD2,
  3. Masahiro Hirayama MD3,
  4. Takako Miyamura MD4,
  5. Michiki Hatanaka MD5,
  6. Yutaka Saikawa MD6,
  7. Eiichi Ishii MD7

Article first published online: 19 FEB 2009

DOI: 10.1002/pbc.21975

Issue

Pediatric Blood & Cancer

Pediatric Blood & Cancer

Volume 52, Issue 7, pages 808–813, 1 July 2009

Additional Information

How to Cite

Tomizawa, D., Koh, K., Hirayama, M., Miyamura, T., Hatanaka, M., Saikawa, Y. and Ishii, E. (2009), Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: A report from the Japan infant leukemia study group. Pediatric Blood & Cancer, 52: 808–813. doi: 10.1002/pbc.21975

Author Information

  1. 1

    Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan

  2. 2

    Department of Pediatrics, University of Tokyo, Tokyo, Japan

  3. 3

    Department of Pediatrics, Mie University, Tsu, Japan

  4. 4

    Department of Pediatrics, Okayama University, Okayama, Japan

  5. 5

    Department of Pediatrics, Fukuoka University, Fukuoka, Japan

  6. 6

    Department of Pediatrics, Kanazawa Medical University, Ishikawa, Japan

  7. 7

    Department of Pediatrics, Ehime University, Toon, Japan

*Department of Pediatrics and Developmental Biology, Postgraduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 1138519, Japan.

Publication History

  1. Issue published online: 7 APR 2009
  2. Article first published online: 19 FEB 2009
  3. Manuscript Accepted: 15 JAN 2009
  4. Manuscript Received: 21 OCT 2008

Funded by

  • Japan Leukemia Research Fund
  • Japan Children's Cancer Association
  • Ministry of Health and Welfare of Japan

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Keywords:

  • infant acute lymphoblastic leukemia;
  • MLL gene;
  • recurrent;
  • refractory

Abstract

Background

Despite the poor outcome of recurrent or refractory acute lymphoblastic leukemia (ALL) in infants with MLL gene rearrangement, few studies have focused on this specific group. We conducted a retrospective analysis of infants with recurrent or refractory ALL from two previous consecutive Japanese studies to clarify the characteristics and prognostic factors among these patients

Procedure

All recurrent or refractory ALL infants with MLL gene rearrangement (MLL-R) who were registered in two consecutive Japanese nation-wide multicentric trials (MLL96 and MLL98; between 1995 and 2001) were eligible for the study.

Results

Among 80 MLL-R ALL infants, 34 cases of recurrence and 5 induction failures occurred. The median duration of first remission was 5 months (range, 0–28 months). All patients underwent various salvage chemotherapies; remission was achieved in 40.5% (15/37). A total of 23 patients received subsequent hematopoietic stem cell transplantations (HSCT): 9 in remission, 12 without remission, and 2 with unknown status. With median follow-up period of 5.5 years, the 5-year overall survival (OS) rate after the second-line treatment was 25.6% ± 6.9%. Young age (<3 months) and central nervous system involvement at initial diagnosis were associated with poor outcome; however, failure to achieve remission after salvage therapy was the sole independent poor prognostic factor in multivariate analysis (P = 0.01).

Conclusions

The prognosis of infants with recurrent or refractory MLL-R ALL is extremely poor despite alternative treatments including HSCT; therefore, it is necessary to develop novel treatment strategies. Pediatr Blood Cancer 2009;52:808–813. © 2009 Wiley-Liss, Inc.

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