PMID- 30677244 OWN - NLM STAT- MEDLINE DCOM- 20200326 LR - 20210109 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 8 IP - 2 DP - 2019 Feb TI - Improved survival outcomes and restoration of graft-vs-leukemia effect by deferasirox after allogeneic stem cell transplantation in acute myeloid leukemia. PG - 501-514 LID - 10.1002/cam4.1928 [doi] AB - Deferasirox is an oral iron-chelating agent having possible antileukemia and immune modulatory effects. Few reports have evaluated deferasirox in the setting of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We investigated the impact of deferasirox after allo-HSCT in acute myeloid leukemia (AML). Of 326 consecutive patients undergoing allo-HSCT in remission, analysis of 198 patients not receiving deferasirox revealed the negative prognostic effect of hyperferritinemia (>/=1000 ng/mL) before and after allo-HSCT on survival mainly due to increase in relapse. Of 276 patients with hyperferritinemia at 1 month after allo-HSCT, 128 patients (46%) received deferasirox. Deferasirox induced a faster decline in serum ferritin level with a manageable safety profile, which significantly reduced relapse rather than nonrelapse mortality, resulting in better survival compared to patients not receiving deferasirox. Of note, the deferasirox group had a significantly higher incidence of chronic graft-vs-host disease, indicating improved graft-vs-leukemia (GVL) effects evidenced by the presence of suppressed regulatory T cells and sustained higher proportion of NK cells in peripheral blood. This study firstly demonstrates the improved survival and restoration of GVL effects of patients with AML by deferasirox, which also clarifies the detrimental effect of hyperferritinemia through after allo-HSCT. CI - (c) 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Cho, Byung-Sik AU - Cho BS AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Jeon, Young-Woo AU - Jeon YW AUID- ORCID: 0000-0003-3362-8200 AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Hahn, A-Reum AU - Hahn AR AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Lee, Tai-Hyang AU - Lee TH AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Park, Sung-Soo AU - Park SS AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Yoon, Jae-Ho AU - Yoon JH AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Lee, Sung-Eun AU - Lee SE AUID- ORCID: 0000-0002-9810-2050 AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Eom, Ki-Seong AU - Eom KS AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Kim, Yoo-Jin AU - Kim YJ AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Lee, Seok AU - Lee S AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Min, Chang-Ki AU - Min CK AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. FAU - Cho, Seok-Goo AU - Cho SG AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. FAU - Lee, Jong-Wook AU - Lee JW AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. FAU - Min, Woo-Sung AU - Min WS AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. FAU - Kim, Hee-Je AU - Kim HJ AD - Division of acute leukemia, Catholic Hematology Hospital, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea. AD - Leukemia Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190124 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Iron Chelating Agents) RN - 9007-73-2 (Ferritins) RN - V8G4MOF2V9 (Deferasirox) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Deferasirox/*therapeutic use MH - Female MH - Ferritins/blood MH - Graft vs Leukemia Effect/*drug effects MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Iron Chelating Agents/*therapeutic use MH - Leukemia, Myeloid, Acute/blood/*therapy MH - Male MH - Middle Aged MH - Treatment Outcome MH - Young Adult PMC - PMC6382990 OTO - NOTNLM OT - acute myeloid leukemia OT - allogeneic hematopoietic stem cell transplantation OT - deferasirox OT - graft-vs-leukemia effects OT - hyperferritinemia EDAT- 2019/01/25 06:00 MHDA- 2020/03/27 06:00 PMCR- 2019/01/24 CRDT- 2019/01/25 06:00 PHST- 2018/10/18 00:00 [received] PHST- 2018/11/26 00:00 [accepted] PHST- 2019/01/25 06:00 [pubmed] PHST- 2020/03/27 06:00 [medline] PHST- 2019/01/25 06:00 [entrez] PHST- 2019/01/24 00:00 [pmc-release] AID - CAM41928 [pii] AID - 10.1002/cam4.1928 [doi] PST - ppublish SO - Cancer Med. 2019 Feb;8(2):501-514. doi: 10.1002/cam4.1928. Epub 2019 Jan 24.