PT-Cy方案联合芦可替尼及托珠单抗预防单倍型相合造血干细胞移植后aGVHD的效果

PT-Cy combined with ruxolitinib and tocilizumab prevents aGVHD after haploidentical HSCT

目的采用单臂前瞻性研究评估PT-Cy(post-transplant cyclophosphamide)方案联合芦可替尼、托珠单抗预防单倍型相合异基因外周血造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后急性移植物抗宿主病(acute graft versus host disease,aGVHD)的疗效。方法收集2019年1月1日至2020年3月1日本院血液科行单倍型相合异基因外周血HSCT的56例患者资料。预防aGHVD方案:环磷酰胺40 mg/kg×2 d(+3^+4 d)+环孢素(+5^+180 d)+麦考酚钠肠溶片(+5^+35 d)+托珠单抗8 mg/kg×1 d(-1 d)+芦可替尼(-1^+180 d);观察移植效果及aGVHD等不良反应发生情况。结果56例患者均成功植入(100%),中性粒细胞植入中位时间为13 d,血小板植入中位时间为17 d;Ⅱ~Ⅳ度aGVHD发生率为23.2%;Ⅲ~Ⅳ度aGVHD发生率为12.5%。1例患者因aGVHD控制不佳导致死亡;6例患者出现肺部感染;12例患者出现人巨细胞病毒感染或病毒拷贝数持续上升;8例患者出现EB病毒感染或病毒拷贝数持续上升;8例患者出现造血受抑。随访2~16个月,中位随访时间8个月,无复发死亡率(nonrelapse mortality,NRM)为7.2%;总生存率(overall survival,OS)为91.4%。结论单倍型相合移植患者采用PT-Cy联合芦可替尼、托珠单抗方案预防aGVHD的效果较好。细菌、病毒感染率未见明显增加,造血受抑发生率较高,整体耐受性良好。

Objective To evaluate the efficacy of post-transplant cyclophosphamide(PT-Cy)combined with ruxolitinib and tocilizumab in the prevention of acute graft versus host disease(aGVHD)after haploidentical allogeneic peripheral blood hematopoietic stem cell transplantation(HSCT)by a single-arm prospective study.Methods A total of 56 patients undergoing haploidentical allogeneic peripheral blood HSCT in our department from January 1,2019 to March 1,2020 were recruited in this study.The GHVD prevention regiments included:cyclophosphamide 40 mg/kg×2 d(+3^+4 d),ciclosporin 2 mg/kg(+5^+180 d)and mycophenolate sodium enteric-coated tablets 10 mg/kg(+5^+35 d),tocilizumab 8 mg/kg×1 d(-1 d),and ruxolitinib(-1^+180 d).The effect of transplantation and adverse effect of aGVHD were observed.Results The implantation of stem cells was completed successfully among all the 56 patients(100%),with an implantation time of neutrophils of 13 d and of platelets of 17 d.The incidence of gradeⅡ~ⅣaGVHD was 23.2%,and that of gradeⅢ~Ⅳwas 12.5%.One patient died due to poor control of aGVHD,6 patients had pulmonary infection;12 patients had human cytomegalovirus infection or persistent viral copy number rise;8 patients had Epstein-Barr virus infection or persistent viral copy number rise;and 8 patients had hematopoietic suppression.During the follow-up of 2~16 months(median 8 months),nonrelapse mortality(NRM)was 7.2%,and overall survival rate(OS)was 91.4%.Conclusion PT-Cy combined with ruxolitinib and tocilizumab regimen can effectively prevent aGVHD for haplotype concomitant transplantation patients.No significant increases of bacterial and viral infections are observed.This program has a higher incidence of hematopoietic suppression and a good overall tolerance.