Devergie A, Apperley J F, Labopin M, Madrigal A, Jacobsen N, Carreras E, Prentice H G, Jouet J P, Kolb H J, Herstenstein B, Bacigalupo A, Evensen S A, Ljungman P, de Witte T, Reiffers J, Nagler A, Clark R E, Goldman J M, Gratwohl A
Hopital Saint Louis, Paris, France.
Bone Marrow Transplant. 1997 Jul;20(1):11-9. doi: 10.1038/sj.bmt.1700844.
We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.
我们回顾性分析了预后因素对慢性粒细胞白血病（CML）患者血清学 HLA 匹配的无关供者（UD）骨髓移植（BMT）结局的影响。为此，我们研究了 1985 年 1 月至 1994 年 12 月间在欧洲接受移植的 366 例患者。211 例男性和 155 例女性的中位年龄为 34 岁；238 例患者在慢性期首次接受移植，116 例在晚期接受移植。从诊断到 BMT 的中位间隔时间为 827 天。202 例患者的移植物抗宿主病（GVHD）预防方案为环孢素 A（CsA）和甲氨蝶呤（MTX），129 例患者采用体外或体内 T 细胞去除（TCD）。最近，基于 DNA 的 HLA - II 类分型方法已用于改善供者选择。我们获得了 300 对供者/受者（D/R）的完整数据。其中，根据特定的 HLA - DRB1 D/R 相容性，我们确定了三组患者。210 例患者接受了 HLA - DRB1 相同的供者的骨髓（第 1 组）。31 例患者接受了 HLA - DRB1 不匹配的供者的 BMT（第 2 组），59 例患者接受了未进行特定 HLA - DRB1 分型的供者的 BMT（第 3 组）。2 年时的总生存率为 37±3%，无白血病生存率（LFS）为 31±3%。单因素分析中，五个变量对 LFS 有有利影响：慢性期首次移植（P = 0.0001）、从诊断到 BMT 的时间间隔短于中位数（P = 0.01）、无 TCD 的 GVHD 预防（P + 0.001）、急性 GVHD < III 级（P = 0.0009）和 HLA - DRB1 D/R 匹配（P = 0.0001）。第 1 组的移植相关死亡率（TRM）为 49±4%，第 2 组为 79±8%，第 3 组为 80±6%（P = 0.0001）。多因素分析证实 HLA - DRB1 匹配是影响生存（P = 0.04）、LFS（P = 0.013）和 TRM（P = 0.0049）的最显著因素。根据这些结果，我们定义了一个“低风险”组，即慢性期首次移植、接受 HLA - DRB1 匹配的供者、无 TCD 作为 GVHD 预防措施的患者。该组的 2 年 LFS、TRM 和复发率分别为 51±5%、47±5%和 2±2%。这表明具有良好预后特征的患者的长期结局可接近同基因同胞移植患者的结局。相比之下，从非 HLA - DRB1 相同的供者接受晚期疾病移植的患者的 TRM 为 94%。如此高的 TRM 清楚地表明这些个体进行 UD BMT 是不合理的。
