LYMPHOCYTES AND LMYPHOKINES IN APLASTIC ANEMIA

再生障碍性贫血中的淋巴细胞和淋巴细胞因子

• 批准号: 3942850
• 负责人: N S YOUNG
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3942850
• 关键词: aplastic anemia; bone marrow disorder; cyclosporines; globulins; hematopoiesis; hematopoietic growth factor; hematopoietic stem cells; human subject; human therapy evaluation; human tissue; immunohematology; immunosuppressive antileukocyte serum; interferons; interleukin 2; lymphocyte; myelofibrosis; thymus

Laboratory and clinical studies have suggested that aplastic anemia may be may immunologically mediated. In a multi-center trial, over 150 patients with aplastic anemia and a variety of hematologic failure syndromes entered a controlled trial of anti- thymocyte globulin (ATG, Upjohn). Approximately 50% of patients with acute severe aplastic anemia had hematologic improvement, usually to transfusion independence, within three months. There were no significant differences between 10 and 28 days of therapy. Patients with chronic severe and moderate aplastic anemia also responded to 10 days of ATG: patients with pancytopenia and cellular bone marrow behaved similarly. However, other hemotologic disorders including myelofibrosis, paroxysmal nocturnal hemoglobinuria, pure red cell aplasia, and amegakaryocytic thrombocytopenia, did not respond to ATG. We have also treated patients with cyclosporin A, an agent with more specific effects on T-cell function. Fifteen patients with severe aplastic anemia who had failed ATG therapy were treated with cyclosporin, for 3 months without and then for 3 months with prednisone. Five responded. All patients recover during the time of combined cyclosporin and corticosteroid therapy, and there have been no relapses. Five patients who received shorter courses of cyclosporin A prior to ATG did not respond. No patients with Diamond- Blackfan syndrome recovered with cyclosporin A, but one of two patients with adult pure red cell aplasia had a complete hemotologic remission. Cyclosporin A as well as ATG appears to be effective therapy in aplastic anemia. Finally, preliminary data has suggested a fundamental immunological defect in aplastic anemia: interleukin I (Il-l) production by monocytes from patients with aplastic anemia is markedly decreased, and, conversely, Il-l production in patients with myelofibrosis, a hyperproliferative disorder, is markedly increased.

实验室和临床研究表明， 贫血可能是免疫介导的。 多中心 试验中，超过150例再生障碍性贫血患者和各种 血液衰竭综合征进入了一项抗- 胸腺细胞球蛋白（ATG，Upjohn）。 大约50%的 急性重型再生障碍性贫血患者血液学检查 改善，通常是输血的独立性，在三个月内 个月 10和28之间没有显著差异 治疗的日子 慢性重度和中度 再生障碍性贫血也对10天的ATG有反应： 全血细胞减少和细胞骨髓表现相似。 然而，其他血液学疾病包括骨髓纤维化， 阵发性睡眠性血红蛋白尿、纯红细胞再生障碍性贫血，以及 无巨核细胞性血小板减少症，对ATG无反应。 我们 也用环孢菌素A治疗患者， 对T细胞功能的特殊影响。 15例重度 ATG治疗失败的再生障碍性贫血患者， 环孢菌素，3个月不使用，然后3个月使用 强的松 五人回答。 所有病人在这段时间内都能康复 联合环孢菌素和皮质类固醇治疗， 没有复发 5名接受较短疗程的患者 环孢菌素A治疗无反应。 没有患者发生 Diamond-Blackfan综合征用环孢菌素A治愈，但 2例成人纯红细胞再生障碍性贫血患者中有1例 血液学完全缓解 环孢菌素A以及ATG 似乎是治疗再生障碍性贫血的有效方法。 最后， 初步数据表明， 再生障碍性贫血的缺陷：白细胞介素I（II-1）的产生 再生障碍性贫血患者的单核细胞 减少，相反，在患有糖尿病的患者中， 骨髓纤维化是一种过度增殖性疾病， 增加