PATHOGENESIS AND TREATMENT OF APLASTIC ANEMIA

再生障碍性贫血和其他形式的骨髓衰竭具有临床和 实验室特征与可能的病毒病因学一致， 免疫病理生理学 特别是再生障碍性贫血， 病毒感染，特别是非甲非乙型肝炎。 患者 他们的免疫系统激活的证据类似于观察到的 许多病毒感染，如细胞毒性淋巴细胞的激活， 淋巴因子分泌过多自然杀伤细胞减少 随着丙型肝炎病毒的最新发现，非甲非乙型肝炎的病原体 肝炎，我们已经测试了再生障碍性贫血可能是 感染丙型肝炎病毒。 然而，使用几种不同的 通过实验方法，我们已经排除了丙型肝炎作为病因 在肝炎/再生障碍综合征和一般再生障碍性贫血中， 虽然我们已经确定丙型肝炎感染是常见的， 在这个病人群体中。 根据这些研究， 在暴发性肝炎患者中，我们认为存在一种新的 肝炎剂，F型肝炎，作为再生障碍性贫血的原因， 暴发性肝炎 我们调查了疱疹病毒的一个成员 家族，巨细胞病毒，与骨髓移植失败有关 移植后。 我们已经确定巨细胞病毒可以 在人巨噬细胞和单核细胞以及造血细胞中增殖 祖细胞而不影响其数量或功能。 重组 巨细胞病毒可以有效地用于治疗的基因转移。 在临床研究中，我们研究了各种造血系统， 生长因子在治疗骨髓疾病中的功效。 最成功的是，我们已经证明白细胞介素-3可以导致完全的 先天性纯红细胞再生障碍性贫血患者的缓解（Diamond-- Blackfan贫血）。 在骨髓增生异常中，G-CSF似乎上级于 GM-CSF或IL-3。 白细胞介素-1还没有被 对难治性再生障碍性贫血患者有效，尽管这些 患者缺乏体外测定的白细胞介素-1产生。 最后我们 已经发起了对严重的免疫抑制的研究， 利用抗胸腺细胞球蛋白的再生障碍性贫血， 环孢菌素;该方案似乎比ATG有显著进步 单独治疗。

Aplastic anemia and other forms of bone marrow failure have clinical and laboratory features consistent with a possible viral etiology followed by immunological pathophysiology. In particular, aplastic anemia may follow on viral infections, especially non-A non-B hepatitis. Patients have evidence of activation of their immune system similar to that observed in many viral infections, such as activation of cytotoxic lymphocytes, excessive lymphokine production, and decreased natural killer cells. With the recent discovery of hepatitis C virus, the agent for non-A non-B hepatitis, we have tested the hypothesis that aplastic anemia may be incited by hepatitis C infection. However, using several different experimental approaches, we have excluded hepatitis C as an etiologic agent in hepatitis/aplasia syndrome and in aplastic anemia in general, although we have established hepatitis C infection as frequent following transfusion in this patient population. Based on these studies and those of patients with fulminant hepatitis, we suggest the existence of a novel hepatitis agent, hepatitis F, as responsible for aplastic anemia and fulminant hepatitis. We have investigated a member of the herpesvirus family, cytolomegalovirus, which is implicated in marrow graft failure following transplantation. We have established that cytomegalovirus can be propagated in human macrophages and monocytes and in hematopoietic progenitor cells without affecting their number or function. Recombinant cytomegalovirus may be useful efficiently for gene transfer for therapy. In clinical studies, we have investigated a variety of hematopoietic growth factors for their efficacy in the treatment of marrow states. Most successfully, we have shown that interleukin-3 can lead to complete remissions in patients with congenital pure red cell aplasia (Diamond-- Blackfan anemia). In myelodysplasia, G-CSF appears to be superior to either GM-CSF or IL-3 in a controlled study. Interleukin-1 has not been effective in patients with refractory aplastic anemia, although these patients lack interleukin-1 production as measured in vitro. Finally, we have instigated studies of intensive immunosuppression for severe aplastic anemia utilizing anti-thymocyte globulin in combination with cyklosporine; this regimen appears to be a significant advance over ATG treatment alone.