Donor KIR3DL1/receptor HLA-Bw4-80I Combination Reduces Acute Leukemia Relapse after Umbilical Cord Blood Transplantation without in Vitro T-cell Depletion

供体 KIR3DL1/受体 HLA-Bw4-80I 组合可减少脐带血移植后急性白血病复发,无需体外 T 细胞耗竭

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作者:Xinchen Fang, Xiaoyu Zhu, Baolin Tang, Kaidi Song, Wen Yao, Xiang Wan, Huilan Liu, Jun Peng, Zimin Sun

Background

Donor natural killer (NK) cell alloreactivity in umbilical cord bone marrow transplantation (UCBT) can lead to leukemic relapse. However, NK cell function is calibrated by interaction with human leukocyte antigens (HLAs). This study aimed to investigate graft-resistant leukemia after transplantation and compared specific genotypes of killer immunoglobulin-like receptors (KIRs) in donors and human leukocyte antigen ligands in patients.

Conclusions

Our data suggest that the donor KIR3DL1/receptor and HLA-Bw4-80I combination in UCBT results in stronger graft-versus-leukemia effects and improved outcomes in patients with acute leukemia.

Methods

We retrospectively analyzed 232 patients with acute leukemia from a single center. Patients had undergone UCBT with myeloablative conditioning and without anti-thymocyte globulin. We identified the KIR genotypes of cord blood donors using polymerase chain reaction with sequence-specific primers. All of the donors contained KIR3DL1.

Results

The patients were divided into three groups according to the HLA-B locus. The donor KIR3DL1 and recipient HLA-Bw4-80I combination was predictive of being highly educated and was associated with a lower relapse (P=0.006) and better overall survival (probability of relapse=0.13, P < 0.001) than the uneducated group. We found no significant increase in the incidence of acute or chronic graft-versus-host disease. Conclusions: Our data suggest that the donor KIR3DL1/receptor and HLA-Bw4-80I combination in UCBT results in stronger graft-versus-leukemia effects and improved outcomes in patients with acute leukemia.

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