Weisdorf D, Hakke R, Blazar B, Miller W, McGlave P, Ramsay N, Kersey J, Filipovich A
Bone Marrow Transplantation Program, University of Minnesota, Minneapolis.
Transplantation. 1991 Jun;51(6):1197-203. doi: 10.1097/00007890-199106000-00010.
We have analyzed factors associated with acute graft-versus-host disease following allogeneic bone marrow transplantation in 469 patients with histocompatible sibling donors between 1979 and 1987. Overall, 46 +/- 5% (95% confidence interval) developed clinical grade II-IV acute GVHD following transplantation. In univariate analysis, patient or donor age greater than or equal to 18 years was significantly associated with increased GVHD risks (greater than or equal to 18, 63 +/- 6% grade II-IV GVHD vs. less than 18, 27 +/- 6%, P less than .0001), without incremental risk in older adults. Univariate analysis showed that donor:recipient sex match and female:female transplants were associated with less-frequent GVHD. More frequent GVHD was associated with chronic myelogenous leukemia, cytomegalovirus seropositivity, and prior donor alloimmunity (pregnancy or transfusion). Additionally, the allele HLA-A26 was associated with increased risk of GVHD (72%, P = .005) while HLA-DR3 was associated with less GVHD (31%, P = .03). Stepwise multivariate analysis confirmed the increased GVHD risks associated with older recipient age, HLA-A26 and donor:recipient gender (not female:female) and the protective effect of HLA-DR3. Similar results were found using the different analytic technique of recursive partition analysis, which identified within the adult population the lowest GVHD risk in female recipients with nonalloimmunized female donors (20%), while other gender combinations had 68% acute GVHD, regardless of donor alloimmunity. In children (less than 18 years), lower GVHD risk accompanied donor:recipient sex-matched (18%) versus mismatched (33%) BMT. Clinical trials undertaken to lessen the hazards of GVHD must be designed with appropriate attention to these reproducibly identified clinical variables associated with different GVHD risks.
我们分析了1979年至1987年间469例具有组织相容性同胞供者的患者在接受异基因骨髓移植后与急性移植物抗宿主病相关的因素。总体而言，46±5%（95%置信区间）的患者在移植后发生了临床II-IV级急性移植物抗宿主病。单因素分析显示，患者或供者年龄大于或等于18岁与移植物抗宿主病风险增加显著相关（大于或等于18岁，63±6%发生II-IV级移植物抗宿主病，而小于18岁者为27±6%，P<0.0001），老年人中无额外风险增加。单因素分析表明，供者与受者性别匹配以及女性与女性之间的移植与移植物抗宿主病发生频率较低相关。移植物抗宿主病发生频率较高与慢性粒细胞白血病、巨细胞病毒血清学阳性以及既往供者同种免疫（妊娠或输血）相关。此外，等位基因HLA-A26与移植物抗宿主病风险增加相关（72%，P = 0.005），而HLA-DR3与移植物抗宿主病发生率较低相关（31%，P = 0.03）。逐步多因素分析证实，受者年龄较大、HLA-A26以及供者与受者性别（非女性与女性）与移植物抗宿主病风险增加相关，而HLA-DR3具有保护作用。使用递归划分分析这一不同分析技术也发现了类似结果，该分析在成年人群中确定，具有未发生同种免疫的女性供者的女性受者移植物抗宿主病风险最低（20%），而其他性别组合的急性移植物抗宿主病发生率为68%，与供者同种免疫无关。在儿童（小于18岁）中，供者与受者性别匹配的骨髓移植（18%）相比不匹配的骨髓移植（33%）移植物抗宿主病风险较低。为降低移植物抗宿主病危害而进行的临床试验设计时必须适当关注这些反复确定的与不同移植物抗宿主病风险相关的临床变量。
