Tocilizumab for the treatment of steroid refractory graft-versus-host disease.
Tocilizumab for the treatment of steroid refractory graft-versus-host disease.
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DOI：
10.1016/j.bbmt.2011.07.001
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Hari P
中科院分区：
文献类型：
--
作者：
Drobyski WR;Pasquini M;Kovatovic K;Palmer J;Douglas Rizzo J;Saad A;Saber W;Hari P
皮质类固醇激素难治性移植物抗宿主病（GVHD）是异基因干细胞移植受者管理的主要挑战之一。虽然许多药物已被用于治疗这一患者人群，但没有标准化的二线治疗。在这项研究中，我们报告了我们的经验与管理托珠单抗，抗白细胞介素6受体抗体，在治疗类固醇难治性GVHD。8例难治性急性（n = 6）或慢性GVHD（cGVHD）（n = 2）患者接受托珠单抗给药，每3 - 4周一次。大多数急性GVHD（aGVHD）患者有IV级器官累及皮肤或胃肠道，而2例cGVHD患者在治疗时均有长期严重的皮肤硬化。未发生过敏或输注相关不良事件。1例患者因担心托珠单抗可能使既存高胆红素血症恶化而停止治疗。一些患者还出现血清转氨酶值一过性升高。感染是与托珠单抗给药相关的主要不良事件。4例aGVHD患者（67%）在治疗的前56天内出现部分或完全缓解。一名cGVHD患者对治疗有显著反应，而第二名患者的疾病稳定，允许适度减少免疫抑制药物。这些结果表明，托珠单抗在类固醇难治性GVHD的治疗中具有活性，并且值得进一步研究作为这种疾病的治疗选择。
Corticosteroid refractory graft-versus-host disease (GVHD) is one of the major challenges in the management of allogeneic stem cell transplant recipients. Although numerous agents have been employed to treat this patient population, no standardized second-line therapy exists. In this study, we report our experience with the administration of tocilizumab, an anti-interleukin 6 receptor antibody, in the treatment of steroid refractory GVHD. Tocilizumab was administered to 8 patients with refractory acute (n = 6) or chronic GVHD (cGVHD) (n = 2) once every 3 to 4 weeks. The majority of patients with acute GVHD (aGVHD) had grade IV organ involvement of the skin or gastrointestinal tract, whereas both patients with cGVHD had long-standing severe skin sclerosis at the time of treatment. There were no allergic or infusion-related adverse events. Treatment was discontinued in one patient over concerns that tocilizumab may have worsened preexisting hyperbilirubinemia. Several patients also had transient elevations in serum transaminase values. Infections were the primary adverse events associated with tocilizumab administration. Four patients (67%) with aGVHD had either partial or complete responses apparent within the first 56 days of therapy. One patient with cGVHD had a significant response to therapy, whereas the second had stabilization of disease that allowed for a modest reduction in immune suppressive medications. These results indicate that tocilizumab has activity in the treatment of steroid refractory GVHD and warrants further investigation as a therapeutic option for this disorder.
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