Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX.
University of Minnesota, Minneapolis, MN.
J Clin Oncol. 2020 Jun 20;38(18):2062-2076. doi: 10.1200/JCO.19.00396. Epub 2020 May 4.
There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.
We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, < .0071 in multivariable analysis and < .00025 in direct pairwise comparisons were considered statistically significant.
In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.
Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
对于缺乏 HLA 匹配的相关或无关供体的造血细胞移植（HCT）患者，对于选择何种替代供体（脐带血[UCB]、单倍体相合、1 个抗原不匹配[7/8]-骨髓[BM]或 7/8-外周血[PB]）尚无共识。
我们报告了 2198 例接受 UCB（n=838）、单倍体相合（n=159）、7/8-BM（n=241）或 7/8-PB（n=960）HCT 的患者的无移植物抗宿主病（GVHD）-无复发存活率（GRFS）和无慢性 GVHD（cGVHD）-无复发存活率（CRFS）的复合终点。除了单倍体相合组大多数接受 RIC 外，所有组均按清髓性或非清髓性预处理（MAC）强度进行分组。为了考虑多次检验，多变量分析中 <.0071，直接两两比较中 <.00025 被认为具有统计学意义。
在多变量分析中，单倍体相合组的 GRFS、CRFS 和总生存率（OS）最佳。在其他组的直接两两比较中，接受 MAC 的患者中，使用血清治疗（阿仑单抗或抗胸腺细胞球蛋白）的 UCB、7/8-BM 和 7/8-PB 组之间的 GRFS 或 CRFS 无差异。相比之下，未使用血清治疗的 7/8-PB 组的 GRFS 明显较差，cGVHD 发生率较高，CRFS 趋势较差（危险比[HR]，1.38；95%CI，1.13 至 1.69；.002），cGVHD 发生率较高，CRFS 趋势较差（HR，1.36；95%CI，1.14 至 1.63；.0006）与 UCB 组相比。在接受 RIC 的患者中，与单倍体相合组相比，所有组的 GRFS 和 CRFS 均明显较差。
鉴于注册回顾性分析的局限性以及选择供体时中心选择偏倚的可能性，我们的数据支持对接受 MAC HCT 的患者使用 UCB、7/8-BM 或 7/8-PB（使用血清治疗）移植物，对接受 RIC HCT 的患者使用单倍体相合移植物。单倍体相合组在所有组中的 GRFS、CRFS 和 OS 最佳。
