Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota.
Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota.
Biol Blood Marrow Transplant. 2019 Jan;25(1):e28-e32. doi: 10.1016/j.bbmt.2018.08.022. Epub 2018 Aug 24.
We previously reported that acute myelogenous leukemia (AML) transplants using killer cell immunoglobulin-type receptor (KIR) B haplotype better or best (≥2 B activating gene loci ± Cen B/B) unrelated donors (URDs) yield less relapse and better survival. In this prospective trial we evaluated 535 AML searches from 14 participating centers with centralized donor KIR genotyping for donor selection. This represented 3% to 48% of all AML searches (median 20%) per center, totaling 3 to 172 patients (median 22) per center. Donor KIR genotype was reported at a median of 14 days after request (≤26 days for 76% of searches). In 535 searches, 2080 donors were requested for KIR genotyping (mean 4.3 per search); and a median of 1.8 (range, 0 to 4.5) per search were KIR typed. Choosing more donors for confirmatory HLA and KIR haplotype identification enriched the likelihood of finding KIR better or best donors. The search process identified a mean of 30% KIR better or best donors; the success ranged from 24% to 38% in the 11 centers enrolling ≥8 patients. More donors requested for KIR genotyping increased the likelihood of identifying KIR better or best haplotype donors. Of the 247 transplants, 9.3% used KIR best, 19% used KIR better, and 48% used KIR neutral donors while 24% used a non-KIR-tested donor. KIR genotyping did not delay transplantation. The time from search to transplant was identical for transplants using a KIR-genotyped versus a non-KIR-genotyped donor. Prospective evaluation can rapidly identify KIR favorable genotype donors, but choosing more donors per search would substantially increase the likelihood of having a KIR best or better donor available for transplantation. Transplant centers and donor registries must both commit extra effort to incorporate new characteristics (beyond HLA, age, and parity) into improved donor selection. Deliberate efforts to present additional genetic factors for donor selection will require novel procedures.
我们之前报道过,使用杀伤细胞免疫球蛋白样受体(KIR)B 单倍型更好或最佳(≥2 B 激活基因座±Cen B/B)非相关供者(URD)的急性髓细胞白血病(AML)移植可以降低复发率和提高生存率。在这项前瞻性试验中,我们评估了来自 14 个参与中心的 535 例 AML 检索,这些中心通过集中供者 KIR 基因分型进行供者选择。这代表了每个中心所有 AML 检索的 3%至 48%(中位数 20%),每个中心总共 3 至 172 名患者(中位数 22 名)。供者 KIR 基因型报告中位数为请求后 14 天(76%的检索请求≤26 天)。在 535 次检索中,请求了 2080 名供者进行 KIR 基因分型(平均每次检索 4.3 名);中位数为 1.8(范围为 0 至 4.5)每次检索都进行 KIR 分型。选择更多的供者进行确认 HLA 和 KIR 单倍型鉴定,可以增加找到 KIR 更好或最佳供者的可能性。检索过程确定了平均 30%的 KIR 更好或最佳供者;在 11 个入组≥8 名患者的中心,成功率从 24%到 38%不等。请求更多的供者进行 KIR 基因分型可以增加确定 KIR 更好或最佳单倍型供者的可能性。在 247 例移植中,9.3%使用 KIR 最佳,19%使用 KIR 较好,48%使用 KIR 中性供者,而 24%使用未经 KIR 检测的供者。KIR 基因分型没有延迟移植。使用 KIR 基因分型供者与未使用 KIR 基因分型供者的移植从检索到移植的时间相同。前瞻性评估可以快速确定 KIR 有利基因型供者,但每个检索选择更多的供者将大大增加可用于移植的 KIR 最佳或更好供者的可能性。移植中心和供者登记处都必须做出额外的努力,将新的特征(超出 HLA、年龄和生育)纳入改进的供者选择。有意努力为供者选择呈现额外的遗传因素将需要新的程序。