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The outcomes of relapsed acute myeloid leukemia in children: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05R study
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  • Hiroshi Moritake,
  • Shiro Tanaka,
  • Takako Miyamura,
  • Hideki Nakayama,
  • Norio Shiba,
  • Akira Shimada,
  • Kiminori Terui,
  • Yuki Yuza,
  • Katsuyoshi Koh,
  • Hiroaki Goto,
  • Harumi Kakuda,
  • Akiko Saito,
  • Daisuke Hasegawa,
  • Shotaro Iwamoto,
  • Takashi Taga,
  • Souichi Adachi,
  • Daisuke Tomizawa
Hiroshi Moritake
University of Miyazaki
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Shiro Tanaka
Graduate School of Medicine and Public Health, Kyoto University
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Takako Miyamura
Osaka University Graduate School of Medicine
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Hideki Nakayama
Kyushu Cancer Center Institute for Clinical Research
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Norio Shiba
Yokohama City University
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Akira Shimada
Okayama University Hospital
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Kiminori Terui
Hirosaki University Graduate School of Medicine
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Yuki Yuza
Tokyo Metropolitan Children's Medical Center
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Katsuyoshi Koh
Saitama Children’s Medical Center
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Hiroaki Goto
Kanagawa Childrens Medical Center
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Harumi Kakuda
Chiba Children's Hospital
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Akiko Saito
National Hospital Organization Nagoya Medical Center
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Daisuke Hasegawa
St. Luke's International Hospital
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Shotaro Iwamoto
Mie University Graduate School of Medicine
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Takashi Taga
Shiga University of Medical Science
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Souichi Adachi
Kyoto University
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Daisuke Tomizawa
National Center for Child Health and Development
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Abstract

Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. Procedure: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. Results: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the non-surviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (p<0.01). Moreover, achieving a second complete remission (CR2) prior to hematopoietic cell transplantation was associated with a good prognosis (p<0.01). Etoposide, cytarabine and mitoxantrone (ECM)- or fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (p<0.01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (p=0.04) and core binding factor-AML, t(8;21) and inv(16), as good prognostic markers (p<0.01). Conclusions: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.

Peer review status:ACCEPTED

27 Jul 2020Submitted to Pediatric Blood & Cancer
27 Jul 2020Submission Checks Completed
27 Jul 2020Assigned to Editor
27 Jul 2020Reviewer(s) Assigned
16 Aug 2020Review(s) Completed, Editorial Evaluation Pending
28 Aug 2020Editorial Decision: Revise Minor
04 Sep 2020Submission Checks Completed
04 Sep 2020Assigned to Editor
04 Sep 20201st Revision Received
06 Sep 2020Review(s) Completed, Editorial Evaluation Pending
06 Sep 2020Editorial Decision: Accept