Hiroshi Moritake1, Shiro Tanaka2, Takako Miyamura3, Hideki Nakayama4, Norio Shiba5, Akira Shimada6, Kiminori Terui7, Yuki Yuza8, Katsuyoshi Koh9, Hiroaki Goto10, Harumi Kakuda11, Akiko Saito12, Daisuke Hasegawa13, Shotaro Iwamoto14, Takashi Taga15, Souichi Adachi16, Daisuke Tomizawa17. 1. Division of Pediatrics, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. 2. Department of Clinical Biostatistics, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 3. Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan. 4. Department of Pediatrics, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 5. Department of Pediatrics, Yokohama City University Hospital, Yokohama, Japan. 6. Department of Pediatrics, Okayama University, Okayama, Japan. 7. Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. 8. Department of Hematology/Oncology, Tokyo Metropolitan Children's Medical Center, Fuchu, Japan. 9. Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan. 10. Division of Hemato-oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan. 11. Department of Hematology/Oncology, Chiba Children's Hospital, Chiba, Japan. 12. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 13. Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan. 14. Department of Pediatrics, Mie University Graduate School of Medicine, Tsu, Japan. 15. Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan. 16. Department of Human Health Sciences, Kyoto University, Kyoto, Japan. 17. Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
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.
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.
Authors: Tara White; Gertjan Kaspers; Jonas Abrahamsson; Nira Arad-Cohen; Daniela Cianci; Jose Fernandez; Shau-Yin Ha; Henrik Hasle; Barbara De Moerloose; C Michel Zwaan; Bianca F Goemans Journal: Br J Haematol Date: 2022-02-04 Impact factor: 8.615