Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Hematol Oncol. 2021 Aug;39(3):380-389. doi: 10.1002/hon.2867. Epub 2021 Apr 13.
Killer cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch has been shown to be protective for acute and chronic graft-versus-host disease (aGVHD, cGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute leukemia. Mesenchymal stem cells (MSC) have been considered as one of the most promising prophylaxis for severe GVHD. However, there are no prospective or retrospective studies determining whether they can work synergistically on GVHD. To investigate the potential influence of KIR matching and MSCs, and their synergism on aGVHD and cGVHD after allo-HSCT in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. Data from 104 patients with AML and 50 patients with ALL treated with allo-HSCT in the transplantation unit were retrospectively analyzed. KIR genotyping was performed by the PCR-SSO method. The amplicons were quantified on the Luminex 200 flow analyzer and analyzed using the Quick-Type for Lifecodes software to generate KIR data. Cox proportional hazards models were used in multivariate analyses. KIR receptor-ligand matching was associated with an increased risk of grade II-IV aGVHD compared to KIR receptor-ligand mismatching (p < 0.001) in AML patients, but KIR ligand-mismatching had no significant effect on aGVHD or cGVHD in ALL patients. In contrast, MSCs reduced the incidence of grade II-IV aGVHD in both AML and ALL patients (AML: p = 0.006; ALL: p = 0.008) regardless of KIR mismatching. The combination of KIR receptor-ligand mismatch and MSC transplantation significantly suppressed grade II-IV aGVHD occurrence in AML patients (p = 0.039). In the KIR mismatch group, the incidence of aGVHD was 2.8% in patients receiving MSC compared to 14.6% in those who did not (p = 0.047). KIR receptor-ligand mismatch, MSC transplantation and their combined use significantly reduced the risk of aGVHD after allo-HSCT. These data provide a clinically applicable strategy to reduce aGVHD, thus improving allo-HSCT outcome.
杀伤细胞免疫球蛋白样受体（KIR）受体-配体不匹配已被证明可预防异基因造血干细胞移植（allo-HSCT）后急性和慢性移植物抗宿主病（aGVHD，cGVHD），allo-HSCT 用于治疗急性白血病。间充质干细胞（MSC）已被认为是预防严重 GVHD 的最有前途的方法之一。然而，目前尚无前瞻性或回顾性研究确定它们是否可以在 GVHD 方面协同作用。为了研究 KIR 配体匹配、MSC 及其在急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）患者 allo-HSCT 后急性移植物抗宿主病（aGVHD）和慢性移植物抗宿主病（cGVHD）中的协同作用。回顾性分析了移植科 104 例 AML 患者和 50 例 ALL 患者的 allo-HSCT 数据。采用 PCR-SSO 法进行 KIR 基因分型。将扩增子在 Luminex 200 流式分析仪上定量，并使用 Quick-Type for Lifecodes 软件进行分析，以生成 KIR 数据。使用 Cox 比例风险模型进行多变量分析。在 AML 患者中，与 KIR 受体-配体不匹配相比，KIR 受体-配体匹配与 II-IV 级 aGVHD 的风险增加相关（p < 0.001），但 KIR 配体不匹配对 ALL 患者的 aGVHD 或 cGVHD 无显著影响。相反，无论 KIR 不匹配如何，MSC 均可降低 AML 和 ALL 患者 II-IV 级 aGVHD 的发生率（AML：p = 0.006；ALL：p = 0.008）。KIR 受体-配体不匹配和 MSC 移植的组合可显著抑制 AML 患者 II-IV 级 aGVHD 的发生（p = 0.039）。在 KIR 不匹配组中，接受 MSC 的患者的 aGVHD 发生率为 2.8%，而未接受 MSC 的患者为 14.6%（p = 0.047）。KIR 受体-配体不匹配、MSC 移植及其联合使用可显著降低 allo-HSCT 后 aGVHD 的风险。这些数据为减少 aGVHD 提供了一种具有临床应用价值的策略，从而改善 allo-HSCT 结局。
