A RETROSPECTIVE ANALYSIS OF THERAPY FOR ACUTE GRAFT-VERSUS-HOST DISEASE - INITIAL TREATMENT
A RETROSPECTIVE ANALYSIS OF THERAPY FOR ACUTE GRAFT-VERSUS-HOST DISEASE - INITIAL TREATMENT
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DOI：
10.1182/blood.v76.8.1464.1464
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发表时间：
1990-10-15
期刊：
影响因子：
20.3
通讯作者：
HANSEN, JA
中科院分区：
文献类型：
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作者：
MARTIN, PJ;SCHOCH, G;HANSEN, JA
我们回顾了 740 名 II-IV 级急性移植物抗宿主病 (GVHD) 患者异基因骨髓移植后的治疗结果。治疗开始时，597 名患者（81%）出现皮疹，369 名患者（50%）出现肝功能障碍，396 名患者（54%）出现肠道功能障碍。初始治疗采用糖皮质激素 (n = 531)、环孢菌素 (n = 170)、抗胸腺细胞球蛋白 (ATG) (n = 156) 或单克隆抗体 (n = 3)，单独使用 (n = 633) 或联合使用 (n = 107)。每周记录每个器官的 GVHD 严重程度参数，并使用二级治疗开始时的值进行反应评估，或者对于未进行此类治疗的患者，使用初级治疗第 29 天的值或死亡前最后记录的值（以先发生者为准）进行反应评估。为每个器官定义了改善或进展的最低标准，但如果存在静脉闭塞性疾病或感染性肠炎等其他并发症，则不会尝试定义肝脏或肠道结果。皮肤病的改善率为 43%，可评估的肝脏疾病的改善率为 35%，可评估的肠道疾病的改善率为 50%。 44% 的患者出现总体完全或部分缓解。进行多变量分析以确定与至少一个器官总体改善的可能性和反应的可能性相关的患者、疾病或治疗因素。我们还进行了类似的分析，以确定与治疗失败时间（定义为开始二次治疗或非由于恶性肿瘤复发而死亡）相关的协变量。在所有三种模型中，与单独使用任一药物进行预防相比，使用环孢素联合甲氨蝶呤进行 GVHD 预防与良好的 GVHD 治疗结果相关，并且糖皮质激素或环孢素的治疗比 ATG 的治疗更成功。与治疗失败时间模型中的不利结果相关且也进入其中一种反应模型的其他因素包括受者与供体的 HLA 差异、存在 GVHD 以外的肝脏并发症以及 GVHD 的早期发作。分析结果表明，糖皮质激素代表了治疗急性 GVHD 的最佳初始疗法，尽管仍有很大的改进空间。
We have reviewed results of therapy in 740 patients with grades II-IV acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucucorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried our to identify covariates associated with time to treatment failure (defined as initiation of seondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favourable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of the analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains.