免疫耐受诱导与血友病治疗。马尔默方案更新。

Immune tolerance induction and the treatment of hemophilia. Malmö protocol update.

作者信息

Berntorp E, Astermark J, Carlborg E

机构信息

Department for Coagulation Disorders, University of Lund, Malmö University Hospital, Sweden.

出版信息

Haematologica. 2000 Oct;85(10 Suppl):48-50; discussion 50-1.

PMID:11187871

Abstract

The Malmö protocol for immune tolerance induction includes high doses of Factor VIII/IX, intravenous IgG and cyclophosphamide. If the inhibitor titer exceeds 10 Bethesda units at start, extracorporeal adsorption of IgG is performed using protein A. The protocol sometimes has to be repeated. A successful response may occur within a few weeks. In hemophilia A the success rate so far is 10/17 patients (15 high-responders, 2 low-responders) or 59%, whereas in hemophilia B 6/9 patients (8 high-responders, 1 low-responder), or 67%, have become tolerant. In one hemophilia B patient, a relapse occurred after 6 months. During a second treatment episode he developed an acute myocardial infarction, probably caused by replacement with prothrombin complex concentrate. We conclude that the Malmö protocol is efficient for induction of immune tolerance but the patients must be selected particularly with regard to inhibitor duration and time of last booster.

摘要

马尔默免疫耐受诱导方案包括大剂量的凝血因子 VIII/IX、静脉注射免疫球蛋白和环磷酰胺。如果开始时抑制剂滴度超过 10 贝塞斯达单位，则使用蛋白 A 对免疫球蛋白进行体外吸附。该方案有时需要重复进行。成功的反应可能在几周内出现。在甲型血友病中，到目前为止成功率为 17 例患者中的 10 例（15 例高反应者，2 例低反应者），即 59%，而在乙型血友病中，9 例患者中的 6 例（8 例高反应者，1 例低反应者），即 67%，实现了耐受。在 1 例乙型血友病患者中，6 个月后出现复发。在第二次治疗期间，他发生了急性心肌梗死，可能是由凝血酶原复合物浓缩物替代治疗引起的。我们得出结论，马尔默方案在诱导免疫耐受方面是有效的，但必须特别根据抑制剂持续时间和最后一次加强注射时间来选择患者。