Fox R A, Neufeld E J, Bennett C M
Department of Medicine, Children's Hospital, Boston, MA, USA.
Haemophilia. 2006 May;12(3):218-22. doi: 10.1111/j.1365-2516.2006.01215.x.
Neutralizing alloantibodies (inhibitors) to factor VIII or factor IX develop in approximately 25% of patients with haemophilia A and <3% of patients with haemophilia B treated with factor concentrate. Patients with high titre inhibitors, in whom immune tolerance therapy fails, have few treatment options. Targeted anti-B-cell therapy with rituximab (chimeric anti-CD20) has been useful in several antibody-mediated autoimmune states. Case reports of rituximab treatment in small numbers of haemophilia patients with inhibitors have been inconclusive. We describe three adolescent patients with severe haemophilia and inhibitors treated with four weekly doses of rituximab, 375 mg m(-2). Treatment with rituximab was effective in reducing the inhibitor titre in two of three patients. Rituximab may be beneficial for patients with severe haemophilia and inhibitors in whom standard therapies have failed, but larger prospective studies are required to determine safety, efficacy and predictors of success.
在接受凝血因子浓缩物治疗的甲型血友病患者中，约25%会产生针对凝血因子VIII的中和性同种抗体（抑制剂），而乙型血友病患者中这一比例<3%。对于高滴度抑制剂且免疫耐受治疗失败的患者，治疗选择很少。利妥昔单抗（嵌合抗CD20抗体）靶向抗B细胞疗法在几种抗体介导的自身免疫状态中已证明有效。少数有抑制剂的血友病患者接受利妥昔单抗治疗的病例报告结果尚无定论。我们描述了3例患有严重血友病且有抑制剂的青少年患者，接受了4周剂量的利妥昔单抗治疗，剂量为375 mg m(-2)。利妥昔单抗治疗使3例患者中的2例抑制剂滴度降低。对于标准疗法失败的严重血友病且有抑制剂的患者，利妥昔单抗可能有益，但需要更大规模的前瞻性研究来确定其安全性、疗效及成功的预测因素。
