非亲缘关系脐带血移植治疗25例血液系统疾病患者的临床研究

Clinical Study of Unrelated Umbilical Cord Blood Transplantation for 25 Patients with Hematological Diseases

本研究观察非亲缘脐带血造血干细胞移植(UCBT)在血液系统疾病患者的植入率、移植物抗宿主病(GVHD)、移植相关死亡(TRM)、复发和生存情况。25例接受UCBT的血液系统疾病患者(儿童8例、成人17例)中。3例接受单份脐带血(CB),22例接受双份脐带血。供/受体低分辨人类白细胞抗原(HLA)配型结果为9例6/6位点相合、16例4-5/6位点相合。在预处理方案中21例采用TBI/Cy±Flu±ATG或BuCy±Flu±ATG,4例采用FC+ATG方案。移植物抗宿主病(GVHD)的预防采用以环孢素(CsA)为主的方案。结果表明,存活超过42 d的20例患者中16例(80.0%)获得植入;粒系植入至移植后42 d的累积发生率为64.0%,中位时间17.0 d;巨核系植入至移植后100 d的累积发生率为60.0%,中位时间35.0 d;II-IV度、III-IV度急性GVHD(aGVHD)至移植后100 d的累积发生率分别为44.0%和30.7%;截止至随访结束日期,移植相关死亡率(TRM)的累积发生率为54.3%;25例患者的总生存率为42.7%;17例可评估恶性血液病患者中7例(41.2%)存活,且仅有1例复发,无事件生存率(EFS)为35.3%;5例可评估的非恶性血液病患者中4例存活,2例处于持续脐血植入状态,2例自身造血恢复;处于疾病进展期的3例患者中仅1例患者存活。结论:低分辨HLA-4-6/6位点相合的UCBT治疗血液系统疾病是可行的,双份脐血移植(dUCBT)可以克服单份脐血细胞数量不足的缺点,可用于治疗大体重儿童及成人患者。

This study was purposed to investigate the engraftment, graft-versus-host disease （GVHD）, transplantation related mortality （TRM）, relapse and survival in hematologic patients received unrelated umbilical cord blood transplantation （UCBT）. A total of 25 patients with hematological disease underwent UCBT, including 8 pediatric and 17 young adult patients. Among them 3 cases received single unit of UCBT and 22 cases received double units of UCBT. For donor/recipients human leukocyte antigen （HLA） matching： HLA 6/6 loci matched in 9 cases, HLA 4 -5/6 loci matched in 16 cases. There were 19 patients with hematologic malignancies, including 3 cases in the period of disease progression and 6 cases of non-hematologic malignancies. Conditioning regimens were TBI/Cy ＋ Flu ＋ ATG or BuCy ＋ Flu ＋ ATG for 21 patients and Cy ＋ Flu ＋ ATG for 4 patients. For prophylaxis of acute graft-versus-host disease （aGVHD） the regimen of cyclosporine （CsA） as dominant drug was used. The results showed that among 16 patients （ 80.0% ） achieved engraftment, 20 patients survived for more than 42 d after transplantation. The cumulative neutrophil recovery rate on day 42 after transplant was 64.0%, with a median time of 17.0 d;the cumulative platelet recovery rateon day 100 after transplant was 60.0 % ,with a median time of 35.0 d. The cumulative rate of grade Ⅱ - IV and Ⅲ - IV aGVHD after transplantation 100 d was 44.0% and 30. 7%, respectively. Until the end of the follow-up, the cumulative rate of TRM was 54. 3%. For all the patients, overall survival rate was 42. 7%. Out of 17 evaluable patients with hematologic malignancies 7 cases （41.2%） survived to date, and only 1 case relapsed, so event-free survival rate was 35. 3 %. Out of 5 evaluable patients with non-hematologic malignancies, 4 patients survived and 2 patients were in stable engraftment state, 2 cases with autologous hematopoietic recovery. Among 3 cases of hematologic malignancies at advanced stage, only 1 case survived to date. It is concluded that HLA-4 - 6/6 loci matched UCBT is an effective option to treat hematological diseases. Double cord blood transplantation （dUCBT） can overcome the disadvantage of insufficient cells of single cord blood UCBT to treat overweight children and adult.