Keever-Taylor C A, Bredeson C, Loberiza F R, Casper J T, Lawton C, Rizzo D, Burns W H, Margolis D A, Vesole D H, Horowitz M, Zhang M J, Juckett M, Drobyski W R
Medical College of Wisconsin Bone Marrow Transplant Program, Department of Medicine, Milwaukee, WI 53226, USA.
Biol Blood Marrow Transplant. 2001;7(11):620-30. doi: 10.1053/bbmt.2001.v7.pm11760150.
Multivariate analysis was performed to determine the independent factors affecting the risk of acute GVHD (aGVHD) grades II to IV and extensive chronic GVHD (cGVHD) and the rate of survival in 481 recipients of T cell-depleted (TCD) marrow allografts who received transplants at a single center between 1991 and 2000. All patients received grafts partially depleted of CD3+ T cells by complement-mediated lysis using 2 narrow-specificity monoclonal antibodies (MoAbs), T10B9.1A-31 (n = 400) or Muromonab-Orthoclone OKT3 (n = 81). Factors considered in the analysis included patient/donor sex, age, cytomegalovirus (CMV) status, and ABO blood group along with T-cell dose, disease, and disease status, donor relationship, HLA antigen (Ag)mismatch (MM), growth-factor use, anti-thymocyte globulin use, year of transplantation, and the MoAb used for TCD. The results showed an association of HLA with an increased relative risk (RR) of aGVHD for recipients of grafts from relateddonors that were > or =2 Ag MM (n = 73, RR = 2.09, P = .005), matched unrelated (UR) donors (n = 130, RR = 1.98, P = .004), and > or =2 Ag MM UR donors (n = 34, RR = 2.68, P = .003) compared with the baseline matched-sibling group (n = 121). No increased risk of aGVHD was seen for 0 to 1 Ag MM family donors (n = 24) or 1 Ag MM UR donors (n = 99). aGVHD risk was increased with minor, but not major or major-minor, ABO disparity (RR = 2.0, P = .003) compared with that of ABO-identical pairs. We found less effective TCD and resultant higher T-cell dose for recipients of grafts that were T cell depleted using OKT3. However, the use of OKT3 and not the T-cell dose was associated with increased aGVH-D risk (RR of 1.84, P = .001). Increased risk of extensive cGVHD was associated with patient age of >20 years (RR = 2.2, P < .0001) and with CMV status (positive patient/negative donor, RR = 1.9, P = .002). Decreased survival was associated with older age (>20 years), a > or =2 Ag MM related donor, a 1 or > or =2 Ag MM UR donor, risk group, and a CMV-positive patient/-negative donor pair. There was no difference in survival for 0 to 1 Ag MM related or matched UR donors compared with the baseline group. These data indicate that there are quantitative as well as potential qualitative differences in outcome depending on the TCD method. Expected and unexpected risk factors for GVHD and survival were associated with partial TCD. Our data support the consideration of ABO match in donor selection, the preferential selection of CMV-positive donors for CMV-positive recipients, and the acceptance of 1 but not > or =2 Ag HLA MM donors.
对1991年至2000年间在单一中心接受移植的481例T细胞去除（TCD）骨髓同种异体移植受者进行多变量分析，以确定影响急性移植物抗宿主病（aGVHD）II至IV级、广泛慢性移植物抗宿主病（cGVHD）风险及生存率的独立因素。所有患者均接受了通过使用两种窄特异性单克隆抗体（MoAbs）T10B9.1A - 31（n = 400）或莫罗单抗 - 抗人胸腺细胞球蛋白（Muromonab - Orthoclone OKT3，n = 81）经补体介导的裂解部分去除CD3 + T细胞的移植物。分析中考虑的因素包括患者/供者性别、年龄、巨细胞病毒（CMV）状态、ABO血型以及T细胞剂量、疾病及疾病状态、供者关系、人类白细胞抗原（Ag）错配（MM）、生长因子使用、抗胸腺细胞球蛋白使用、移植年份以及用于TCD的MoAb。结果显示，与基线匹配同胞组（n = 121）相比，来自相关供者且Ag错配≥2的移植物受者（n = 73，相对风险（RR）= 2.09，P = 0.005）、匹配无关（UR）供者（n = 130，RR = 1.98，P = 0.004）以及Ag错配≥2的UR供者（n = 34，RR = 2.68，P = 0.003）发生aGVHD的相对风险增加。0至1个Ag错配的家族供者（n = 24）或1个Ag错配的UR供者（n = 99）未观察到aGVHD风险增加。与ABO血型相同的配对相比，轻微ABO血型不合（但非主要或主要 - 次要不合）时aGVHD风险增加（RR = 2.0，P = 0.003）。我们发现使用OKT3进行T细胞去除的移植物受者的TCD效果较差，导致T细胞剂量较高。然而，与aGVHD风险增加相关的是OKT3的使用而非T细胞剂量（RR为1.84，P = 0.001）。广泛cGVHD风险增加与患者年龄>20岁（RR = 2.2，P < 0.0001）以及CMV状态（患者阳性/供者阴性，RR = 1.9，P = 0.002）相关。生存率降低与年龄较大（>20岁）、Ag错配≥2的相关供者、1个或Ag错配≥2的UR供者、风险组以及CMV阳性患者/阴性供者配对相关。与基线组相比，0至1个Ag错配的相关或匹配UR供者的生存率无差异。这些数据表明，根据TCD方法，结果存在数量以及潜在的质量差异。GVHD和生存的预期及意外风险因素与部分TCD相关。我们的数据支持在供者选择中考虑ABO血型匹配，对于CMV阳性受者优先选择CMV阳性供者，以及接受1个但非Ag错配≥2的HLA供者。
