Michallet M, Perrin M C, Belhabri A, Molina L, Nicolini F, Tigaud J D, Sotto J J, Guyotat D, Fière D, Archimbaud E
Unité de Greffe de Moëlle Osseuse, Service d'Hématologie, Hôpital Edouard Herriot, Lyon, France.
Bone Marrow Transplant. 1999 Jan;23(2):145-50. doi: 10.1038/sj.bmt.1701529.
In order to determine whether doses of cyclosporine and methylprednisolone used for prophylaxis and therapy of acute graft-versus-host disease (GVHD) have any influence on relapse and survival following allogeneic bone marrow transplantation (BMT), we studied 176 adult patients with hematologic malignancies, who underwent a first allogeneic transplant from an HLA-identical sibling donor. Two methods of management of acute GVHD used in two different centers were compared: group I included 62 patients who had 'standard' management of GVHD including prophylaxis with 1-3 mg/kg/day of cyclosporine and treatment with 2 mg/kg/day of methylprednisolone when acute GVHD developed; group II included 114 patients who received 'intensive' management of GVHD including prophylaxis with 5 mg/kg/day of cyclosporine and treatment with high-dose methylprednisolone (8-20 mg/kg/day for 3 days) at the onset of GVHD. The overall incidence of GVHD was the same in both groups. However, acute GVHD was more severe in group I than in group II (P < 0.0001), with consequently less resolution of GVHD after treatment in group I (61%) than in group II (80%) (P = 0.06). Overall survival and disease-free survival (DFS) did not differ between the two groups. However, actuarial risk of disease relapse was significantly higher in group II than in group I (36% vs 17%, P = 0.02). In a multivariate analysis taking into account known factors influencing GVHD and relapse, only type of GVHD management and age were significantly predictive for the occurrence of GVHD, while only type of GVHD management and pathology other than chronic myeloid leukemia (CML) were predictive for relapse. This study demonstrates that intensity of GVHD prophylaxis and therapy can influence the graft-versus-leukemia effect by decreasing severity of GVHD but at the price of increasing relapse rate post transplant.
为了确定用于预防和治疗急性移植物抗宿主病（GVHD）的环孢素和甲基强的松龙剂量对异基因骨髓移植（BMT）后的复发和生存是否有任何影响，我们研究了176例患有血液系统恶性肿瘤的成年患者，他们接受了来自HLA相同同胞供体的首次异基因移植。比较了两个不同中心使用的两种急性GVHD管理方法：第一组包括62例接受GVHD“标准”管理的患者，包括用1 - 3mg/kg/天的环孢素进行预防，急性GVHD发生时用2mg/kg/天的甲基强的松龙进行治疗；第二组包括114例接受GVHD“强化”管理的患者，包括用5mg/kg/天的环孢素进行预防，GVHD发作时用高剂量甲基强的松龙（8 - 20mg/kg/天，共3天）进行治疗。两组GVHD的总体发生率相同。然而，第一组的急性GVHD比第二组更严重（P < 0.0001），因此第一组治疗后GVHD的缓解率（61%）低于第二组（80%）（P = 0.06）。两组的总生存率和无病生存率没有差异。然而，第二组疾病复发的精算风险显著高于第一组（36%对17%，P = 0.02）。在一项考虑了影响GVHD和复发的已知因素的多变量分析中，只有GVHD管理类型和年龄对GVHD的发生有显著预测作用，而只有GVHD管理类型和除慢性粒细胞白血病（CML）以外的病理类型对复发有预测作用。这项研究表明，GVHD预防和治疗的强度可以通过降低GVHD的严重程度来影响移植物抗白血病效应，但代价是移植后复发率增加。
