EFFECTS OF ANTI-INTERFERON ANTIBODIES IN HAIRY CELL LEUKEMIA

我们已经观察到干扰素耐药性的发展 接受干扰素α-2a治疗并患有 它与抗干扰素抗体的发展有关。 在16名干扰素α-2a中和抗体阳性的患者中， 6例对该疗法产生临床耐药。原因是什么 其余10名患者对干扰素仍敏感。 面子上的抗体还不清楚，这就是目的 试验以观察这些抗体对人类免疫系统的影响 干扰素α-2a对毛发患者的生物学效应 细胞性白血病。所有参加这项研究的患者都有毛细胞。 他患有白血病，过去曾接受过干扰素治疗。 患者将接受单剂干扰素α-2a和 2‘-5’-寡腺苷合成酶活性的系列评估 外周血单核细胞，血清新喋呤水平， 干扰素药代动力学和对干扰素的发热反应 都会被制造出来。预计中和治疗的患者 抗体将在一定程度上抑制所有这些生物学上的 干扰素α-2a的作用。因为所有中和抗体 在我们的患者中检测到只中和干扰素α-2a和 不是天然干扰素的部分纯化制剂，这些 患者随后将接受一剂人类淋巴母细胞 干扰素和这些相同的生物终点被确定。如果， 正如预期的那样，患者确实有正常的生物学特征 面对人类淋巴母细胞干扰素的应答性 对干扰素α-2a的抗体，就会得出结论 对疾病有抵抗力的细胞白血病患者重组 干扰素α-2a可能对人类的治疗有反应 淋巴母细胞类干扰素。

We have observed the development of interferon resistance in a number of patients receiving interferon alfa-2a treatments and have correlated it with the development of anti-interferon antibodies. Of 16 patients with neutralizing antibodies to interferon alfa-2a, 6 developed clinical resistance to this therapy. The reason why the remaining 10 patients remained sensitive to interferon in the face of antibodies is not clear, and it is the purpose of this trial to look at effects that these antibodies might have on the biological effects of interferon alfa-2a in patients with hairy cell leukemia. All patients entered on this study have hairy cell leukemia and will have been treated with interferon in the past. Patients will receive a single dose of interferon alfa-2a and serial assessments of 2'-5'oligoadenylate synthetase activity in peripheral blood mononuclear cells, serum neopterin levels, interferon pharmacokinetics, and the fever response to interferon will be made. It is anticipated that patients with neutralizing antibodies will have some inhibition of all of these biological effects of interferon alfa-2a. Because all neutralizing antibodies detected in our patients neutralized only interferon alfa-2a and not a partially purified preparation of natural interferon, these patients will subsequently receive a dose of human lymphoblastoid interferon and these same biological end points determined. If, as is anticipated, patients do have normal biological responsiveness to human lymphoblastoid interferon in the face of antibodies to interferon alfa-2a, it will be concluded that hairy cell leukemia patients with disease resistance to recombinant interferon alfa-2a will likely be responsive to therapy with human lymphoblastoid interferon.