巴利昔单抗短期替代钙调蛋白抑制剂预防急性移植物抗宿主病的探索性研究

Short-term substitution of calcineurin inhibitors(CNI)with recombinant humanized anti-CD25 monoclonal antibody(Basiliximab)as aGVHD prophylaxis in CNI intolerant patients after allogeneic hematopoietic stem cell transplantation

目的探讨在钙调蛋白抑制剂(CNI)不耐受患者中短期应用重组抗CD25人源化单克隆抗体巴利昔单抗(Basiliximab)单药预防异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(GVHD)的有效性。方法本研究纳入2021年8月至2022年8月在上海闸新中西医结合医院骨髓移植科行挽救性allo-HSCT后因CNI严重不良反应而应用巴利昔单抗预防急性GVHD的17例难治性恶性血液病患者。男7例,女10例,中位年龄43(18~67)岁。停用CNI后,给予巴利昔单抗1 mg/kg每周1次进行替代预防,直至患者有条件重新启用CNI或哺乳动物雷帕霉素靶体蛋白(mTOR)抑制剂。结果巴利昔单抗的替代预防中位开始时间为移植后5(1~32)d,替代治疗中位持续时间为20(7~120)d。所有患者均获得粒细胞植入,中位植入时间12(10~17)d。13例患者获得血小板植入,中位植入时间13(11~20)d。8例(47.1%)患者发生Ⅱ~Ⅳ度急性GVHD,4例(23.6%)发生Ⅲ/Ⅳ度急性GVHD。仅有1例患者死于急性GVHD。至随访截止,17例患者中7例死亡,存活患者中随访最长时间为347 d,中位生存时间未达到,移植后6个月总生存率为62.6%。17例患者中,13例(76.4%)发生巨细胞病毒再激活,7例(41.2%)发生EB病毒激活,未发生巨细胞病毒病。结论在allo-HSCT过程中出现CNI不耐受时,短期单药应用巴利昔单抗可作为急性GVHD的替代预防方案。

Objectives To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody(Basiliximab)as acute GVHD(aGVHD)prophylaxis in calcineurin inhibitors(CNI)intolerant patients following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI.There were seven men and ten women,with a median age of 43 years(18-67).Following the discontinuation of CNI,Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed.Results Basiliximab was started at an average of 5(1-32)days after HSCT.The median duration of substitution was 20(7-120)days.All had neutrophil engraftment within a median of 12(10-17)days.Thirteen patients had platelet engraftment after a median of 13(11-20)days.Four patients did not develop stable platelet engraftment.Eight patients(47.1%)developed Grade Ⅱ-Ⅳ aGVHD,while four(23.6%)developed Grade Ⅲ/IV aGVHD.Only one patient died from aGVHD.Before the end of the followup period,seven of 17 patients died.The longest followup period of the survivors was 347 days,and the median survival rate was not met.The overall survival(OS)rate at six months was 62.6%.Among the 17 patients,13(76.4%)experienced cytomegalovirus reactivation,7(41.2%)experienced EB virus activation,and no cytomegalovirus disease was observed.Conclusions When CNI intolerance occurs during allo-HSCT,short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.