Prospective randomization of post-remission therapy comparing autologous peripheral blood stem cell transplantation versus high-dose cytarabine consolidation for acute myelogenous leukemia in first remission
- 375 Downloads
We prospectively compared outcomes of autologous stem cell transplantation (ASCT) versus high-dose cytarabine (HiDAC) consolidation as post-remission therapy for favorable- and intermediate-risk acute myelogenous leukemia (AML) in first complete remission (CR1). Two-hundred-forty patients under 65 years with AML-M1, M2, M4, or M5 subtypes were enrolled. After induction, 153 patients did not undergo randomization, while the remaining 87 who achieved CR1 were prospectively randomized to HiDAC (n = 45) or ASCT arm (n = 42). In the HiDAC arm, 43 patients completed three cycles of HiDAC, whereas in ASCT arm 22 patients completed two cycles of consolidation consisting of intermediate-dose cytarabine plus mitoxantrone or etoposide followed by ASCT. The three-year disease-free survival (DFS) rate was 41% in HiDAC and 55% in ASCT arm (p = 0.25). Three-year overall survival (OS) rates were 77 and 68% (p = 0.67). Incidence of relapse was 54 and 41% (p = 0.22). There was no significant difference in nonrelapse mortality between two arms (p = 0.88). Patients in the ASCT arm tended to have higher DFS rates and lower relapse rates than patients in HiDAC; however, there was no significant improvement in OS in patients with favorable- and intermediate-risk AML in CR1. Patients with AML are not benefited by the intensified chemotherapy represented by ASCT.
KeywordsAML Post-remission ASCT HiDAC
We thank the medical and nursing staff working on the JSCT for providing patient information. This work was supported by a Grant from the Regional Medicine Research Foundation (Tochigi, Japan). This work was also supported by a Grant-in-Aid for Scientific Research (no. 16H05340 to T.M.) and Grant-in-Aid for Scientific Research on Innovative Areas “Stem Cell Aging and Disease” (no. 25115002 to T.M.).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest. T.M., K.N., and M.H. designed this study, collected clinical information, and wrote the manuscript. S.T, K.T, G.Y, S.Y, H.H, K.K, K.O, T.A., H.I, H.H, T.T, and K.A contributed to the collection of clinical information. All authors read and approved the final manuscript.
- 1.Mrozek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP, et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012;30(36):4515–23.CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96(13):4075–83.PubMedGoogle Scholar
- 5.O’Donnel MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Bhatt V, et al. NCCN clinical practice guidelines in oncology. AML. NCCN guidelines version 3. 2017. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed 13 Dec 2017.
- 8.Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301(22):2349–61.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995;332(4):217–23.CrossRefPubMedGoogle Scholar
- 11.Suciu S, Mandelli F, de Witte T, Zittoun R, Gallo E, Labar B, et al. Allogeneic compared with autologous stem cell transplantation in the treatment of patients younger than 46 years with acute myeloid leukemia (AML) in first complete remission (CR1): an intention-to-treat analysis of the EORTC/GIMEMAAML-10 trial. Blood. 2003;102(4):1232–40.CrossRefPubMedGoogle Scholar
- 14.Gorin NC, Labopin M, Frassoni F, Milpied N, Attal M, Blaise D, et al. Identical outcome after autologous or allogeneic genoidentical hematopoietic stem-cell transplantation in first remission of acute myelocytic leukemia carrying inversion 16 or t(8;21): a retrospective study from the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol. 2008;26(19):3183–8.CrossRefPubMedGoogle Scholar
- 16.Usuki K, Kurosawa S, Uchida N, Yakushiji K, Waki F, Matsuishi E, et al. Comparison of autologous hematopoietic cell transplantation and chemotherapy as postremission treatment in non-M3 acute myeloid leukemia in first complete remission. Clin Lymphoma Myeloma Leuk. 2012;12(6):444–51.CrossRefPubMedGoogle Scholar
- 18.Harada M, Akashi K, Hayashi S, Eto T, Takamatsu Y, Teshima T, et al. Granulocyte colony-stimulating factor-combined marrow-ablative chemotherapy and autologous blood cell transplantation for the treatment of patients with acute myelogenous leukemia in first remission. The Fukouka Bone Marrow Transplant Group. Int J Hematol. 1997;66(3):297–301.CrossRefPubMedGoogle Scholar
- 20.Eto T, Takase K, Miyamoto T, Ohno Y, Kamimura T, Nagafuji K, et al. Autologous peripheral blood stem cell transplantation with granulocyte colony-stimulating factor combined conditioning regimen as a postremission therapy for acute myelogenous leukemia in first complete remission. Int J Hematol. 2013;98(2):186–96.CrossRefPubMedGoogle Scholar
- 22.Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhauser M, Juliusson G, et al. The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012;9(10):579–90.CrossRefPubMedGoogle Scholar
- 23.Paschka P, Dohner K. Core-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation? Hematol Am Soc Hematol Educ Program. 2013;2013:209–19.Google Scholar
- 39.The Leukemia & Lymphoma Society. Study seeks new AML therapies. Cancer Discov. 2016;6(12):1297–8.Google Scholar