Yoon Jae-Ho, Kim Hee-Je, Park Sung-Soo, Jeon Young-Woo, Lee Sung-Eun, Cho Byung-Sik, Eom Ki-Seong, Kim Yoo-Jin, Lee Seok, Min Chang-Ki, Cho Seok-Goo, Kim Dong-Wook, Lee Jong-Wook, Min Woo-Sung
Department of Hematology, Catholic Blood and Marrow Transplantation Center, Leukemia Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Oncotarget. 2017 Jun 20;8(25):41590-41604. doi: 10.18632/oncotarget.15295.
Standard therapy for acute myeloid leukemia (AML) consists of hematopoietic cell transplantation (HCT) including autologous-HCT (AUTO) and allogeneic-HCT from a matched-sibling donor (MSD) or well-matched unrelated donor (WM-URD). When a conventional donor is not available, HCT from a partially-matched (PM)-URD or familial-mismatched donor (FMMD) is typically considered. We analyzed 561 patients with intermediate to poor-risk molecular cytogenetics who underwent transplant from 2002 to 2013 in their first remission. Engraftment was successful in all donor types except five patients who died in aplasia. Disease-free survival (DFS) at 5 years was 61.4% for MSD, 62.1% for WM-URD, 65.3% for FMMD, 44.7% for AUTO and 36.8% for PM-URD. AUTO showed the highest relapse rate (51.0%) compared to MSD (23.5%) and FMMD (18.5%), but showed the lowest 5-year non-relapse mortality (NRM) rate (3.8%). PM-URD showed the highest NRM (29.3%) with more instances of acute graft-vs.-host disease (GVHD) with grade≥III (29.3%), compared to MSD (15.6%) and FMMD (15.7%). In a poor-risk subgroup, the 5-year DFS for FMMD and MSD was 59.8% and 46.7%, respectively, while for AUTO and PM-URD it was 12.6% and 0.0%, respectively, which was caused by a high relapse rate (87.1% in AUTO, 83.3% in PM-URD). In the intermediate-risk subgroup, the 5-year DFS of AUTO (53.9%) was not different from the conventional donors in multivariate analysis, presenting a low NRM rate (5.1%). FMMD should be considered prior to PM-URD in intermediate-to-poor-risk AML and GVHD prophylaxis should be intensified when PM-URD is needed. AUTO might be considered for selected patients in the intermediate-risk group.
急性髓系白血病(AML)的标准治疗包括造血细胞移植(HCT),其中包括自体造血细胞移植(AUTO)以及来自匹配同胞供体(MSD)或高度匹配无关供体(WM-URD)的异基因造血细胞移植。当无法获得传统供体时,通常会考虑采用部分匹配(PM)-URD或家族性错配供体(FMMD)进行造血细胞移植。我们分析了561例中危至高危分子细胞遗传学患者,这些患者在2002年至2013年首次缓解期接受了移植。除5例死于再生障碍的患者外,所有供体类型的植入均成功。MSD的5年无病生存率(DFS)为61.4%,WM-URD为62.1%,FMMD为65.3%,AUTO为44.7%,PM-URD为36.8%。与MSD(23.5%)和FMMD(18.5%)相比,AUTO的复发率最高(51.0%),但5年非复发死亡率(NRM)最低(3.8%)。PM-URD的NRM最高(29.3%),≥III级急性移植物抗宿主病(GVHD)的发生率更高(29.3%),而MSD为15.6%,FMMD为15.7%。在高危亚组中,FMMD和MSD的5年DFS分别为59.8%和46.7%,而AUTO和PM-URD分别为12.6%和0.0%,这是由于复发率高(AUTO为87.1%,PM-URD为83.3%)所致。在中危亚组中,多因素分析显示AUTO的5年DFS(53.9%)与传统供体无差异,NRM率较低(5.1%)。对于中危至高危AML患者,应在PM-URD之前考虑FMMD,当需要PM-URD时应加强GVHD预防。对于中危组的特定患者可考虑AUTO。