The outcomes of relapsed acute myeloid leukemia in children: Results from the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05R study

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation (HCT) 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 nonsurviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (P <.01). Moreover, achieving a second complete remission (CR2) prior to HCT was associated with a good prognosis (P <.01). Etoposide, cytarabine, and mitoxantrone (ECM)- or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (P <.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 =.04) and core binding factor-AML, t(8;21), and inv(16) as good prognostic markers (P <.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.

Original languageEnglish
Article numbere28736
JournalPediatric Blood and Cancer
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • FLT3-ITD
  • core binding factor
  • pediatric acute myeloid leukemia
  • reinduction therapy
  • relapse

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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