4.4 Article

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

Journal

PEDIATRIC BLOOD & CANCER
Volume 68, Issue 1, Pages -

Publisher

WILEY
DOI: 10.1002/pbc.28736

Keywords

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

Funding

  1. Grant forPractical Research for Innovative Cancer Control from the Japan Agency for Medical Research andDevelopment (AMED) [20ck0106604h0001]
  2. Miyazaki University Hospital

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The prognosis of relapsed pediatric AML depends on the duration from diagnosis to relapse and achieving a second complete remission (CR2) prior to HCT. Treatment with ECM or FLAG-based regimens may improve outcomes, while genetic factors like FLT3-internal tandem duplication can serve as poor prognostic markers.
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 ofFMS-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.

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