Bay Jacques-Olivier, Dhédin Nathalie, Goerner Martin, Vannier Jean-Pierre, Marie-Cardine Aude, Stamatoullas Aspasia, Jouet Jean-Pierre, Yakoub-Agha Ibrahim, Tabrizi Reza, Faucher Catherine, Diez-Martin Jose-Luis, Nunez Gomez, Parody Rocio, Milpied Noël, Espérou Helène, Garban Frédéric, Galambrun Claire, Kwiatkovski Fabrice, Darlavoix Isabelle, Zinaï Amina, Fischer Alain, Michallet Mauricette, Vernant Jean-Paul
Unité de transplantation médullaire, Centre Jean Perrin, Clermont-Ferrand, France.
Transplantation. 2005 Sep 27;80(6):782-8. doi: 10.1097/01.tp.0000173995.18826.de.
The use of monoclonal antibodies against interleukin-2 receptor (IL-2R)-alpha chains could be an effective treatment of acute graft-versus-host disease (GvHD). Experimental model and clinical studies have reported various results.
Inolimomab is a murine anti-IL-2R. Eighty-five patients were evaluated retrospectively for the safety and efficacy of inolimomab given for the treatment of steroid-resistant acute GvHD (aGvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Diseases were immune deficiency, hematological malignancies, or solid tumors. Seventy-six percent of the patients received a myeloablative regimen. The source of HSCT was bone marrow for 45 patients, peripheral blood for 36 patients, and cord blood for 4 patients. Donors were 49 siblings and 36 unrelated. Acute GvHD was diagnosed within a median of 28 days after transplantation (grade II, 26 patients; grade III, 26 patients; grade IV, 33 patients). Inolimomab was administered in the event of steroid-resistant aGvHD with a median dose of 0.468 mg per kg (median period of treatment: 18 days).
Twenty-five complete responses and 29 partial responses (total response rate: 63%) were observed with no side effects. There was no correlation between aGvHD grading and quality of response. Better responses were observed in cutaneous aGvHD. The overall survival probability was 26% (median follow-up: 20 months). Fifty-seven percent of patients died of toxicity related mortality, mostly aGvHD. Response to inolimomab seemed sustained (11% relapse in responders).
Inolimomab is well-tolerated and effective for severe steroid-resistant aGvHD. The optimum regimen remains to be defined.
使用抗白细胞介素-2受体（IL-2R）α链的单克隆抗体可能是治疗急性移植物抗宿主病（GvHD）的有效方法。实验模型和临床研究报告了各种结果。
依诺利单抗是一种鼠抗IL-2R。对85例接受异基因造血干细胞移植（HSCT）后因类固醇难治性急性移植物抗宿主病（aGvHD）而接受依诺利单抗治疗的患者进行了回顾性安全性和疗效评估。疾病包括免疫缺陷、血液系统恶性肿瘤或实体瘤。76%的患者接受了清髓性方案。HSCT的来源为45例患者的骨髓、36例患者的外周血和4例患者的脐带血。供体为49名同胞和36名无关供者。急性移植物抗宿主病在移植后中位28天内确诊（Ⅱ级，26例患者；Ⅲ级，26例患者；Ⅳ级，33例患者）。在出现类固醇难治性aGvHD时给予依诺利单抗，中位剂量为每千克0.468毫克（中位治疗期：18天）。
观察到25例完全缓解和29例部分缓解（总缓解率：63%），且无副作用。aGvHD分级与缓解质量之间无相关性。在皮肤aGvHD中观察到更好的缓解。总生存概率为26%（中位随访：20个月）。57%的患者死于毒性相关死亡率，主要是aGvHD。对依诺利单抗的反应似乎持续（缓解者中11%复发）。
依诺利单抗对严重类固醇难治性aGvHD耐受性良好且有效。最佳方案仍有待确定。
