Outcome of children with relapsed acute myeloid leukemia following initial therapy under the AML99 protocol
- 772 Downloads
The outcomes of children with relapsed acute myeloid leukemia (AML) are known to be poor, but remain obscure. We retrospectively analyzed 71 patients who had relapsed following first-line treatment under the AML99 protocol. We investigated the time and site of recurrence, response to re-induction therapy, and performance of hematopoietic stem cell transplantation (HSCT) in relapsed cases, and performed a multivariate analysis to identify prognostic factors. The 5-year overall-survival (OS) rate after relapse was 37 %. Of 71 patients, three died without any anti-leukemic therapy and two underwent allogeneic HSCT. The remaining 66 patients received re-induction chemotherapy, and 33 (50 %) achieved second CR (CR2). Twenty-two of 25 (88 %) late relapse patients and 11 of 41 (27 %) early relapse patients achieved CR2 (P < 0.001). Twenty-nine CR2 cases and 35 non-CR2 cases underwent allogeneic HSCT. The 5-year OS rate was significantly higher in patients who underwent HSCT in CR2 than those in non-CR2 (66 vs. 17 %, P < 0.000001). Multivariate analysis indicated that early relapse (P < 0.05) and the positivity of the FMS-like tyrosine kinase 3—internal tandem duplication (P < 0.05) were adverse prognostic factors for survival. In conclusion, the etiology of relapsed pediatric AML needs to be elucidated and effective chemotherapy should be administered to obtain CR2.
KeywordsAcute myeloid leukemia (AML) Relapse Children Hematopoietic stem cell transplantation (HSCT) Second complete remission (CR2)
The authors deeply appreciate the invaluable cooperation by the large number of physicians working at institutions affiliated to The Japanese Childhood AML Cooperative Study Group and The Japanese Pediatric Leukemia/Lymphoma Study Group. Research was supported by Grant-in-Aid for Cancer Research from the Ministry of Health, Labor, and Welfare of Japan.
Conflict of interest
The authors declare no conflict of financial interest.
- 1.Tsukimoto I, Tawa A, Horibe K, Tabuchi K, Kigasawa H, Tsuchida M, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group. J Clin Oncol. 2009;27:4007–13.PubMedCrossRefGoogle Scholar
- 2.Imamura T, Iwamoto S, Kanai R, Shimada A, Terui K, Osugi Y, et al. Outcome in 146 patients with pediatric acute myeloid leukemia treated according to the AML99 protocol in the period 2003–06 from the Japan Association of Childhood Leukemia Study. Br J Haematol. 2012;159:204–10.PubMedCrossRefGoogle Scholar
- 4.Aladjidi N, Auvrigno A, Leblanc T, Perel Y, Berard A, Bordigoni P, et al. Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology. J Clin Oncol. 2003;21:4377–85.PubMedCrossRefGoogle Scholar
- 5.Wells RJ, Adams MT, Alonzo TA, Arceci RJ, Buckley J, Buxton AB, et al. Mitoxantrone and cytarabine induction, high-dose cytarabine, and etoposide intensification for pediatric patients with relapsed or refractory acute myeloid leukemia: children’s Cancer Group Study 2951. J Clin Oncol. 2003;21(15):2940–7.PubMedCrossRefGoogle Scholar
- 12.Yamamoto Y, Kiyoi H, Nakano Y, et al. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001;31:187–90.Google Scholar
- 13.Shimada A, Taki T, Tabuchi K, Tawa A, Horibe K, Tsuchida M, et al. KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood. 2006;107:1806–9.PubMedCrossRefGoogle Scholar
- 14.Shimada A, Taki T, Tabuchi K, Taketani T, Hanada R, Tawa A, et al. Tandem duplication of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: a study of the Japanese childhood AML cooperative Study Group. Pediatr Blood Cancer. 2008;50(2):264–9.PubMedCrossRefGoogle Scholar
- 20.Von Neuhoff C, Reinhardt D, Sander A, Zimmermann M, Bradtke J, Betts DR, et al. Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98. J Clin Oncol. 2010;28(16):2682–9.CrossRefGoogle Scholar
- 22.Fleischhack G, Hassan C, Graf N, Mann G, Bode U. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol. 1998;102(3):647–55.PubMedCrossRefGoogle Scholar
- 31.Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001;98:1752–9.PubMedCrossRefGoogle Scholar
- 34.Shimada A, Taki T, Koga D, Tabuchi K, Tawa A, Hanada R, et al. High WT1 mRNA expression after induction chemotherapy and FLT3-ITD have prognostic impact in pediatric acute myeloid leukemia: a study of the Japanese Childhood AML Cooperative Study Group. Int J Hematol. 2012;96(4):469–76.PubMedCrossRefGoogle Scholar
- 37.The Japan Society for Hematopoietic Cell Transplantation Annual Report of Nationwide Survey 2012, JSHCT monograph, vol. 38, p. 97–127 (in Japanese), ISSN 1344-5898.Google Scholar