非血缘脐血移植治疗阵发性睡眠性血红蛋白尿症疗效分析

Application of umbilical cord blood transplantation in the treatment of paroxysmal nocturnalhemoglobinuria

目的探讨单份非血缘脐血移植(UCBT)治疗成人阵发性睡眠性血红蛋白尿症(PNH)的可行性及疗效。方法回顾性分析2014年5月至2019年12月安徽省立医院血液科7例应用单份UCBT治疗成人PNH受者的临床资料。7例受者中6例重度PNH,1例极重度PNH。原发性PNH 4例,PNH-再生障碍性贫血(AA)综合征3例。男性5例,女性2例,中位年龄29岁(20~47岁),中位体重60 kg(50~71 kg),诊断至移植中位时间为62.5个月(7.7~171个月),全部受者均伴输血依赖。预处理方案:清髓性6例,减低强度1例。预防移植物抗宿主病(GVHD)方案均为环孢素A联合短程吗替麦考酚酯,均未使用抗胸腺细胞免疫球蛋白(ATG)。输入脐血有核细胞的中位数为2.4×10^(7)/kg(1.71~4.28×10^(7)/kg),其中输入CD34+细胞中位数为1.58×10^(5)/kg(0.88~3.02×10^(5)/kg)。结果所有受者均获得髓系及红系植入,中性粒细胞绝对计数≥0.5×10^(9)/L的中位时间17 d(15~21 d),网织红细胞计数≥1%的中位时间27 d(22~45 d)。6例受者获得血小板植入,血小板≥20×10^(9)/L中位时间37 d(25~101 d),血小板≥50×10^(9)/L中位时间62 d(27~157 d)。100 d急性GVHD发生率28.6%(95%CI 0~55.3%),其中2例Ⅱ度急性GVHD,仅1例受者发生局限慢性GVHD。全部受者中位随访时间13.5个月(3~71.4个月),6例受者存活,1例PNH-AA综合征伴铁过载受者死于消化道出血。2年总存活率为83.3%(95%CI 27.3~97.5%)。结论单份UCBT治疗PNH,可获得很好的植入率及存活率,PNH-AA综合征伴铁过载可能是影响患者预后的重要因素之一。

Objective To explore the feasibility and efficacy of umbilical cord blood transplantation(UCBT)in the treatment of paroxysmal nocturnal hemoglobinuria(PNH).Methods From May 2014 to December 2019,clinical data were retrospectively reviewed for 7 PNH patients undergoing UCBT.The grades were severe(n=6)and extremely severe(n=1).The causes were primary PNH(n=4)and PNH-aplastic anemia(AA)syndrome(n=3).There were 5 males and 2 females with a median age of 29(20-47)years,a median weight of 60(50-71)kg and a median time from diagnosis to transplantation of 62.5(7.7-171)months.All of them were accompanied by transfusion dependence.Myeloablative(n=6)and reduced-intensity(n=1)pretreatment was offered.The regimen of preventing GVHD was cyclosporine A plus short-term mycophenolate mofetil without ATG.The median number of input nucleated cells was 2.4(1.71-4.28)×10^(7)/kg and the median number of CD34+cells 1.58(0.88-3.02)×10^(5)/kg.Results Neutrophil and erythroid engraftment was obtained with a median neutrophil engraftment time of 17(15-21)days and a median erythroid engraftment time of 27.Engraftment time of 37(25-101)days for platelets>20×10^(9)/L and 62(27-157)days for platelets>50×10^(9)/L.The incidence of 100-day acute GVHD was 28.6%(95%CI 0-55.3%).The severity of GVHD was gradeⅡ°acute(n=2)and mild(n=1).The median follow-up period was 13.5(3-71.4)months.Six patients survived while another with PNH-AA syndrome with iron overload died of gastrointestinal hemorrhage.The 2-year overall survival rate was 83.3%(95%CI 27.3-97.5%).Conclusions With excellent engraftment and survival in the treatment of PNH,UCBT is indicated for patients without HLA full-match donor.PNH-AA syndrome with iron overload may be one of the important prognostic factors.