PATHOGENESIS AND TREATMENT OF APLASTIC ANEMIA

再生障碍性贫血和其他形式的骨髓衰竭有临床和 实验室特征与可能的病毒病原学一致 免疫病理生理学。特别是，再生障碍性贫血可能随之而来 关于病毒感染，特别是非甲非乙型肝炎。患者有 他们的免疫系统被激活的证据与在 许多病毒感染，如细胞毒性淋巴细胞的激活， 淋巴因子产生过多，自然杀伤细胞减少。 随着最近丙型肝炎病毒的发现，非甲非乙肝的病原体 肝炎，我们已经验证了再生障碍性贫血可能是 由丙型肝炎感染引发。但是，使用几种不同的 实验方法，我们已经排除了丙型肝炎的病因 治疗肝炎/再生障碍性贫血和再生障碍性贫血的药物， 尽管我们已经确定丙型肝炎感染是经常发生的 在这个患者群体中进行输血。基于这些研究和那些 对于重型肝炎患者，我们建议存在一种新的 肝炎病原体，F型肝炎，导致再生障碍性贫血和 暴发性肝炎。我们调查了疱疹病毒的一名成员 细胞巨细胞病毒家族，与骨髓移植失败有关 在移植后。我们已经确定巨细胞病毒可以 在人巨噬细胞、单核细胞和造血细胞中繁殖 祖细胞在不影响其数量或功能的情况下。重组 巨细胞病毒可有效地用于基因转移治疗。 在临床研究中，我们研究了各种造血细胞 影响其治疗骨髓状态疗效的生长因子。 最成功的是，我们已经证明了白介素3可以导致 先天性纯红细胞再生障碍性贫血的缓解(钻石-- Blackfan贫血)。在骨髓发育不良中，G-CSF似乎优于 在一项对照研究中使用GM-CSF或IL-3。白介素1还没有被 对难治性再生障碍性贫血患者有效，尽管这些 根据体外测量，患者缺乏白细胞介素1的产生。最后，我们 发起了对重症患者强化免疫抑制的研究 抗胸腺细胞球蛋白联合应用于再生障碍性贫血 环孢素；这一方案似乎比ATG有显著的进步 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.