Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21231, USA.
Biol Blood Marrow Transplant. 2010 Apr;16(4):482-9. doi: 10.1016/j.bbmt.2009.11.011. Epub 2010 Jan 18.
Although some reports have found an association between increasing HLA disparity between donor and recipient and fewer relapses after allogeneic blood or marrow transplantation (BMT), this potential benefit has been offset by more graft-versus-host disease (GVHD) and nonrelapse mortality (NRM). However, the type of GVHD prophylaxis might influence the balance between GVHD toxicity and relapse. The present study analyzed the impact of greater HLA disparity on outcomes of a specific platform for nonmyeloablative (NMA), HLA-haploidentical transplantation. A retrospective analysis was performed of 185 patients with hematologic malignancies enrolled in 3 similar trials of NMA, related donor, haploidentical BMT incorporating high-dose posttransplantation cyclophosphamide for GVHD prophylaxis. No significant association was found between the number of HLA mismatches (HLA-A, -B, -Cw, and -DRB1 combined) and risk of acute grade II-IV GVHD (hazard ratio [HR] = 0.89; P = .68 for 3-4 vs fewer antigen mismatches). More mismatching also had no detrimental effect on event-free survival (on multivariate analysis, HR = 0.60, P = .03 for 3-4 vs fewer antigen mismatches and HR = 0.55, P = .03 for 3-4 vs fewer allele mismatches). Thus, greater HLA disparity does not appear to worsen overall outcome after NMA haploidentical BMT with high-dose posttransplantation cyclophosphamide.
尽管一些报告发现供体和受体之间 HLA 差异增加与同种异体血液或骨髓移植(BMT)后复发减少之间存在关联,但这种潜在益处已被更多的移植物抗宿主病(GVHD)和非复发死亡率(NRM)所抵消。然而,GVHD 预防类型可能会影响 GVHD 毒性和复发之间的平衡。本研究分析了更大的 HLA 差异对特定非清髓性(NMA)、HLA 单倍体相合移植平台的结果的影响。对 185 例血液系统恶性肿瘤患者进行了回顾性分析,这些患者参加了 3 项相似的 NMA、相关供体、单倍体相合 BMT 试验,这些试验均采用高剂量移植后环磷酰胺预防 GVHD。未发现 HLA 错配(HLA-A、-B、-Cw 和 -DRB1 联合)数量与急性 II-IV 级 GVHD 风险之间存在显著关联(危险比 [HR] = 0.89;P =.68,3-4 个 vs 少于 4 个抗原错配)。更多的错配对无事件生存也没有不利影响(多变量分析,HR = 0.60,P =.03,3-4 个 vs 少于 4 个抗原错配和 HR = 0.55,P =.03,3-4 个 vs 少于 4 个等位基因错配)。因此,在接受高剂量移植后环磷酰胺治疗的 NMA 单倍体相合 BMT 后,更大的 HLA 差异似乎不会导致总体结果恶化。