【摘要】 目的 观察allo-HSCT后复发的恶性血液病患者行二次移植治疗的效果，探讨影响二次移植疗效的相关因素。方法 回顾性分析2013年4月—2020年12月河南省肿瘤医院allo-HSCT后复发行二次移植治疗的21例恶性血液病患者的临床资料。21例中二次移植更换供者移植2例，原供者移植19例(同胞全合供者移植15例，无关供者移植2例，单倍体移植2例),2次移植间隔时间为7.7(2.6,104.4)个月。19例原供者移植者采用个体化减低强度的清髓预处理方案，2例更换供者移植者采用强化疗/放疗清髓预处理方案。二次移植后10例采用环孢素单药或联合短疗程甲氨蝶呤和/或吗替麦考酚酯预防移植物抗宿主病(GVHD),11例采用减量的后置环磷酰胺预防GVHD。根据原发病控制及GVHD情况，8例同胞全合移植者采用减量免疫抑制剂诱导移植物抗白血病效应。绘制Kaplan-Meier生存曲线，比较二次移植后有慢性GVHD与无慢性GVHD者、2次移植间隔>6个月与≤6个月者的2年总生存率。结果 (1)21例二次移植后均达到粒细胞系植入，植活时间为13(11,22)d; 20例获得巨核细胞系植入，植活时间为18(11,60)d。allo-HSCT后复发至二次移植的时间为0.7(0.2,10.0)个月。(2)1例死于预处理毒性，余20例均可耐受清髓预处理，无严重并发症发生。(3)二次移植后发生病毒感染4例，肺部感染12例，肠道感染3例，胆囊感染3例，尿路感染、中心静脉导管相关血流感染、皮肤软组织感染、血栓性微血管病、出血性膀胱炎各1例，无肝静脉闭塞综合征发生。(4)二次移植后生存时间>100 d者17例，其中11例发生局限性慢性GVHD,6例未发生慢性GVHD。(5)随访至2022年12月，随访11.6(0.8,88.9)个月，9例生存，12例死亡，2年总生存率为42.9%;8例2次移植间隔<6个月者生存11.7(1.4,14.3)个月。12例死亡者中感染死亡7例(更换供者移植2例，原供者移植5例),复发死亡5例(均为同胞全合移植)。(6)有慢性GVHD者二次移植后2年总生存率[(51.9±23.2)%]高于无慢性GVHD者[(10.0±9.5)%](χ~2=11.424,P=0.001),2次移植间隔≤6个月者二次移植后2年总生存率[(18.8±15.8)%]与2次移植间隔>6个月者[(46.2±16.7)%]比较差异无统计学意义(χ~2=2.812,P=0.102)。结论 allo-HSCT后复发的恶性血液病患者预后差；尽快制订二次移植方案，制订个体化减低强度的清髓预处理方案，二次移植后通过诱导移植物抗白血病效应减少复发，可使部分患者生存获益。更多还原

【Abstract】 Objective To evaluate the efficacy of secondary allo-HSCT in patients with relapsed malignant hematologic diseases and to explore factors influencing the outcomes of secondary allo-HSCT.Methods A retrospective analysis was conducted in 21 patients with malignant hematologic diseases who underwent secondary allo-HSCT after relapse in Henan Cancer Hospital from April 2013 to December 2020,among whom 2 patients involved donor replacement,while 19utilized the original donor(15 from matched sibling donors,2 from unrelated donors,and 2 from haploidentical donors).The median allo-HSCT interval was 7.7(2.6,104.4) months.Nineteen patients with original donor transplantation employed an individualized reduced-dose myeloablative preconditioning regimen,while 2 patients with donor-replacement utilized intensive chemotherapy/radiotherapy myeloablative preconditioning.Following secondary allo-HSCT,10 patients received cyclosporine monotherapy or combined with short-course methotrexate and/or mycophenolate mofetil,and 11patients received reduced-dose post-transplantation cyclophosphamide for graft-versus-host disease(GVHD) prophylaxis.Based on the status of the primary disease and GVHD,8 patients who underwent matched sibling donor transplantation received reduced-dose immunosuppression to induce graft-versus-leukemia effects.Kaplan-Meier survival curves were plotted to compare the 2-year overall survival rates between patients with and without chronic GVHD after secondary transplantation,and between those with an interval of >6 months and≤6 months.Results(1) All 21 patients achieved granulocyte engraftment after secondary transplantation,with a median engraftment time of 13(11,22) d;20 patients achieved megakaryocyte engraftment,with a median engraftment time of 18(11,60) d.The median time from relapse to secondary allo-HSCT was 0.7(0.2,10.0) months.(2) One patient died of preconditioning toxicity,and the remaining 20patients tolerated myeloablative preconditioning without severe complications.(3) The infections after secondary allo-HSCT included viral infections in 4 patients,pulmonary infections in 12,intestinal infections in 3,gallbladder infections in 3,urinary tract infections in 1,central venous catheter-related bloodstream infections in 1,skin and soft tissue infections in 1,thrombotic microangiopathy in 1,and hemorrhagic cystitis in 1.No hepatic vein occlusion syndrome developed.(4) Seventeen patients survived>100 d after secondary allo-HSCT,among whom 11 developed localized chronic GVHD,while 6 remained free of chronic GVHD.(5) The follow-up was conducted until December 2022,with a median follow-up duration of 11.6(0.8,88.9) months;9 patients survived and 12 patients died,with 2-year overall survival rate of 42.9%.The median survival was 11.7(1.4,14.3) months in 8 patients with an interval of <6 months.In 12 deaths,7 patients(2 of donor-replacement transplantation,and 5 of original donor transplantation) died of infection,and 5 died of relapse after matched sibling donor transplantation.(6) The 2-year overall survival rate was higher in patients with chronic GVHD after secondary transplantation [(51.9±23.2)%] than that in patients without chronic GVHD [(10.0±9.5) %](χ~2=11.424,P=0.001),and showed no significant difference between patients with an interval of ≤6 months [(18.8±15.8)%] and> 6 months [(46.2±16.7)%](χ~2=2.812,P=0.102).Conclusions Patients with relapsed malignant hematologic diseases after allo-HSCT generally have a poor prognosis.To formulate a secondary transplantation protocol and an individualized reduced-dose myeloablative preconditioning regimen,and to minimize relapse by inducing graft-versus-leukemia effects after secondary transplantation may improve the survival outcomes of some patients.更多还原