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异基因造血干细胞移植治疗中高危骨髓增生异常综合征:CD34 分选与未修饰造血干细胞移植的疗效比较。

Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome: Comparison of Outcomes between CD34 Selected and Unmodified Hematopoietic Stem Cell Transplantation.

机构信息

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.

Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, Texas.

出版信息

Biol Blood Marrow Transplant. 2018 May;24(5):1079-1087. doi: 10.1016/j.bbmt.2018.01.001. Epub 2018 Jan 8.

Abstract

In this study, we compared transplantation outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with advanced myelodysplastic syndrome (MDS) who received a CD34 cell-selected and those who received an unmodified allograft. This analysis initially included 181 patients, 60 who received a CD34 cell-selected transplant and 121 who received an unmodified transplant. Owing to significant differences in disease characteristics, the analysis was limited to patients with <10% blasts before HSCT (n = 145). Two groups were defined: low risk, with low- and intermediate-risk cytogenetics (CD34, n = 39; unmodified, n = 46), and high risk: poor and very poor risk cytogenetics (CD34, n = 19; unmodified, n = 41). In the low-risk group, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) at 1 year post-transplantation was 18% in the CD34 subgroup versus 41.3% in the unmodified subgroup (P = .015). There were no differences between the subgroups in the incidence of grade III-IV aGVHD. The incidence of chronic graft-versus-host disease (cGVHD) at 3 years in the 2 subgroups was 5.3% and 56%, respectively (P < .001). At 3 years post-transplantation, relapse, overall survival (OS), and relapse-free survival (RFS) were similar in the CD34 and unmodified subgroups: 8.1% versus 19.4% (P = .187), 58.5% versus 53.7% (P = .51), and 59.5% versus 52.4% (P = .448). However, the composite outcome combining extensive cGVHD-free status and relapse-free status (CRFS) at 3 years was 59.5% in the CD34 group versus 19.2% in the unmodified group (P < .001). In the high-risk group, grade II-IV aGVHD at 1 year was 31.6% in the CD34 subgroup versus 24.4% in the unmodified subgroup (P = .752). There were no differences between the subgroups in the incidence of grade III-IV aGVHD. The incidence of cGVHD at 3 years in the 2 subgroups was 0% versus 27.6% (P = .013). At 3 years post-transplantation, relapse, OS, RFS, and CRFS in the 2 subgroups were 31.6% versus 69.3% (P = .007), 35.5% versus 14.5% (P = .068), 31.6% versus 10.7% (P = .045), and 31.6% versus 6.1% (P = .001), respectively. Cytogenetic abnormalities at diagnosis and transplant type had significant univariate associations with RFS in the high-risk cohort. Only cytogenetics (P = .03) remained associated with this outcome in a multivariate model. OS was similar in the 2 transplant groups; however, CRFS was superior in the CD34 cell-selected transplant group.

摘要

在这项研究中,我们比较了接受 CD34 细胞选择移植和未修饰同种异体造血干细胞移植(HSCT)的晚期骨髓增生异常综合征(MDS)患者的移植结果。该分析最初包括 181 名患者,其中 60 名接受 CD34 细胞选择移植,121 名接受未修饰移植。由于疾病特征存在显著差异,因此分析仅限于 HSCT 前<10%blasts 的患者(n=145)。将患者分为两组:低危组,低危和中危细胞遗传学(CD34,n=39;未修饰,n=46);高危组:不良和极差细胞遗传学(CD34,n=19;未修饰,n=41)。在低危组中,移植后 1 年时,CD34 亚组中 II-IV 级急性移植物抗宿主病(aGVHD)的发生率为 18%,而未修饰亚组为 41.3%(P=.015)。两个亚组中 III-IV 级 aGVHD 的发生率没有差异。两组在移植后 3 年时慢性移植物抗宿主病(cGVHD)的发生率分别为 5.3%和 56%(P<.001)。移植后 3 年时,CD34 组和未修饰组的复发、总生存率(OS)和无复发生存率(RFS)相似:8.1%比 19.4%(P=.187),58.5%比 53.7%(P=.51),59.5%比 52.4%(P=.448)。然而,CD34 组和未修饰组在移植后 3 年时广泛 cGVHD 无复发状态和无复发状态(CRFS)的复合结局分别为 59.5%和 19.2%(P<.001)。在高危组中,移植后 1 年时,CD34 亚组中 II-IV 级 aGVHD 的发生率为 31.6%,而未修饰亚组为 24.4%(P=.752)。两个亚组中 III-IV 级 aGVHD 的发生率没有差异。两个亚组在移植后 3 年时 cGVHD 的发生率分别为 0%和 27.6%(P=.013)。移植后 3 年时,两个亚组的复发、OS、RFS 和 CRFS 分别为 31.6%比 69.3%(P=.007)、35.5%比 14.5%(P=.068)、31.6%比 10.7%(P=.045)和 31.6%比 6.1%(P=.001)。高危组中,诊断时的细胞遗传学异常和移植类型与 RFS 有显著的单变量相关性。只有细胞遗传学(P=.03)在多变量模型中与该结果相关。两组的 OS 相似;然而,CRFS 在 CD34 细胞选择移植组中更优。

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