Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial
Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial
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DOI：
10.1182/blood.v97.6.1590
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发表时间：
2001-03-15
期刊：
影响因子：
20.3
通讯作者：
Fischer, A
中科院分区：
文献类型：
--
作者：
Haddad, E;Paczesny, S;Fischer, A
实体器官或骨髓移植后严重的T细胞免疫缺陷可能导致潜伏性EB病毒感染的B细胞不受控制地生长，导致B淋巴细胞增殖性疾病（BLPD）。考虑到IL-6在BLPD中潜在的重要致病作用，测试了单克隆抗IL-6抗体对IL-6的体内中和是否有助于控制BLPD。在12名移植器官的接受者中评估了安全性和有效性，这些接受者在8天内对免疫抑制的减少具有抗性。5例患者接受0.4 mg/kg/天。接下来的7例患者接受0.8 mg/kg/天。治疗计划持续15天。10例患者完成了研究，另外2例患者因疾病进展提前停药（分别为第10天和第13天）。治疗耐受性良好，未观察到重大副作用。治疗前9例患者中发现高C反应蛋白水平，但所有患者治疗后均恢复正常，表明有效的IL-6中和。完全缓解（CR）5例，部分缓解（PR）3例。在观察到缓解的8例患者中，1例患者复发。这种复发对治疗无反应。1例患者病情稳定，但3例患者病情进展。七个病人活得很好。2例患者因疾病进展死亡，3例患者在CR时死亡（2例患者发生慢性排斥反应，1例患者发生BLPD后遗症）。提示抗IL-6抗体治疗BLPD是安全的，值得进一步探讨。（血液，2001;97：1590-1597）（C）2001年由美国血液学会。
Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD, Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe end should be further explored In the treatment of BLPD. (Blood, 2001;97:1590-1597) (C) 2001 by The American Society of Hematology.