KIR haplotype B donors but not KIR-ligand mismatch result in a reduced incidence of relapse after haploidentical transplantation using reduced intensity conditioning and CD3/CD19-depleted grafts

KIR haplotype B donors but not KIR-ligand mismatch result in a reduced incidence of relapse after haploidentical transplantation using reduced intensity conditioning and CD3/CD19-depleted grafts
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KIR 单倍型 B 供体而非 KIR 配体错配导致使用降低强度调节和 CD3/CD19 耗尽的移植物进行单倍相合移植后复发率降低

DOI:
10.1007/s00277-014-2084-2
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发表时间:
2014
影响因子:
3.5
通讯作者:
Bethge WA
Bethge WA
中科院分区:
医学3区
文献类型:
--
作者:
Michaelis SU;Mezger M;Bornhäuser M;Trenschel R;Stuhler G;Federmann B;Oevermann L;Kanz L;Handgretinger R;Bethge WA

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同种异体造血细胞移植(HCT)后自然杀伤细胞(NK)的同种异体反应性受到供体NK细胞上杀伤细胞免疫球蛋白样受体(KIRs)和受体细胞上人类白细胞抗原(HLA) I类配体相互作用的影响。我们研究了供体KIR单倍型和KIR配体不匹配(MM)对57例接受单倍体相同HCT治疗的血液病患者在降低强度调节和移植物CD3/CD19去除后复发的影响。57例供体中,17例为KIR A单倍型(29.8%),40例为KIR B单倍型(70.2%)。57例患者中有34例(59.6%)发现kirr配体MM。供体KIR单倍型在非复发死亡率方面没有差异(NRM,p= 0.200),但单倍型B供体患者的复发发生率显著降低(p= 0.001)。特别是,部分缓解(PR)患者比完全缓解(CR,p= 0.297)患者受益更多(p= 0.008)。评估kir -配体MM的累积复发率(p= 0.680)或NRM (p= 0.579),我们发现无显著差异。总之,在降低强度调节(RIC)和CD3/ cd19缺失的单倍相同HCT的情况下,我们无法证实KIR配体MM的阳性数据,但观察到KIR单倍型B供体的复发风险显着降低。
Natural killer (NK)-cell alloreactivity after allogeneic hematopoietic cell transplantation (HCT) is influenced by the interaction of killer-cell immunoglobulin-like receptors (KIRs) on donor NK cells and human leukocyte antigen (HLA) class I ligands on recipient cells. We investigated the influence of donor KIR haplotype and KIR-ligand mismatch (MM) on relapse in 57 patients with hematologic malignancies receiving haploidentical HCT after reduced intensity conditioning and graft CD3/CD19 depletion. Of the 57 donors, 17 had KIR haplotype A (29.8 %) and 40 had KIR haplotype B (70.2 %). A KIR-ligand MM was found in 34 of 57 patients (59.6 %). There was no difference between donor KIR haplotypes in non-relapse mortality (NRM,p= 0.200) but had a significantly reduced incidence of relapse for patients with a haplotype B donor (p= 0.001). In particular, patients in partial remission (PR) benefited more from a haplotype B graft (p= 0.008) than patients in complete remission (CR,p= 0.297). Evaluating KIR-ligand MM cumulative incidences of relapse (p= 0.680) or NRM (p= 0.579), we found no significant difference. In conclusion, in the setting of reduced intensity conditioning (RIC) and CD3/CD19-depleted haploidentical HCT, we could not confirm the positive data with KIR-ligand MM but observed a significant lower risk of relapse with a KIR haplotype B donor.
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