探讨高危急性白血病患者接受非血缘脐血移植(UCBT)的临床疗效。

回顾性分析东南大学附属中大医院血液科2014年3月至2016年4月经UCBT治疗的14例高危急性白血病患者的临床资料。移植前疾病状态：第1次完全缓解(CR1)6例，第2次完全缓解(CR2)4例，疾病进展期(初发未缓解或复发未缓解)4例。10例患者接受单份脐血移植，4例接受双份脐血移植。12例患者采用清髓性不含抗胸腺细胞球蛋白(ATG)预处理方案，2例HLA 4/6相合患者加用ATG。采用环孢素联合吗替麦考酚酯(MMF)预防移植物抗宿主病(GVHD)。采用Spearman秩相关分析输注CD34^＋细胞计数与血小板植入时间、急性GVHD发生率与脐血相合程度的关系以及影响OS的相关因素；应用Kaplan-Meier法评估患者移植2年累积及3年预期总生存率(OS)、无白血病生存率(LFS)及GVHD无复发生存率(GRFS)。

随访至2017年10月，中位随访时间为27.5个月(1～42个月)，随访期间4例患者死亡，2例死亡原因为复发，2例为感染。14例患者中，1例移植后40 d死于面部软组织感染，其余13例均于移植后30 d内获得中性粒细胞植入，植入中位时间为17 d(11～ 29 d)。12例于移植后60 d内获得血小板植入，血小板植入中位时间为33 d(25～59 d)。输注CD34^＋细胞计数同血小板植入时间相关(r＝－0.62，P<0.05)。急性GVHD发生率与脐血相合程度相关(r＝－0.55，P<0.05)。移植后100 d内11例患者尿CMV-DNA拷贝数升高，持续中位时间为22 d(6～50 d)。患者中有3例复发，其原发病均为急性淋巴细胞白血病；10例移植前达CR1和CR2患者中9例随访期间未复发。患者移植后6个月KPS评分中位数为95分(80～100分)，环孢素、MMF、糖皮质激素停药中位时间分别为移植后113、35、116 d。以Kaplan-Meier法估算患者2年累积及3年预期OS、LFS及GRFS均为72%。移植相关死亡率为14.2%。影响OS的相关因素为：患者移植后中性粒细胞植入时间(r＝－0.70，P<0.05)，移植前疾病状态( r＝－0.67，P<0.05)。

对于高危急性白血病患者，UCBT是良好的治疗选择。UCBT后植入率高、GVHD发病率低、复发率低、GRFS高，移植后早期可停用免疫抑制剂，使高危急性白血病患者获得更高质量的远期生存。

To evaluate the clinical efficacy of umbilical cord blood transplantation (UCBT) on patients with high-risk acute leukemia.

The clinical data of 14 patients with high-risk acute leukemia who got UCBT in the Department of Hematology of Zhongda Hospital Affiliated to Southeast University from March 2014 to April 2016 were retrospectively analyzed. Pretransplant disease status: 6 patients got first complete remission (CR1) after chemotherapy, 4 cases got second complete remission (CR2) after chemotherapy, 4 patients were in the state of disease progression (non-remission after incipience or recurrence). Ten patients received single cord blood transplantation and 4 patients received double cord blood transplantation. 12 patients were pretreated with myeloablative and were not treated with anti-thymocyte globulin (ATG), and 2 HLA 4/6 matched patients received ATG. All the patients received both cyclosporin and mycophenolate mofetil(MMF) to prevent acute graft-versus-host disease (GVHD). The relationship between the number of transfused CD34⁺ cells and implantation time of platelet, and the relationship between incidence rate of GVHD and compatibility of cord blood were both analysed by Spearman rank correlation. Influencing factors of overall survival (OS) were also analysed by Spearman rank correlation. Two-year accumulative and 3-year probability of OS, leukemia-free-survival (LFS), GVHD-free/ relapse-free survival (GRFS) were evaluated by Kaplan-Meier method.

The median follow-up time was 27.5 months (1-42 months) up to October 2017. Four patients died during the follow-up period (2 patients died of relapse and 2 patients died of infection). One case died of facial soft tissue infection 40 days after transplantation, and the other 13 cases got neutrophil implantation within 30 days after transplantation. The median time of neutrophil implantation was 17 days (11-29 d). Platelets were implanted in 12 cases within 60 days after transplantation, and the median time of platelet implantation was 33 days (25-59 d). The number of transfused CD34⁺ cells was related to the time of platelet implantation (r=-0.62, P<0.05). The incidence of acute GVHD was associated with the compatibility of cord blood (r=-0.55, P<0.05). The number of CMV-DNA copies in urine increased in 100 days after transplantation, and the median duration was 22 days (6-50 d). Three patients whose protopathy was acute lymphoblastic leukemia suffered a relapse after transplantation. Ten patients got CR1 or CR2 before transplantation, among which 9 patients did not relapse during follow-up. The median KPS score was 95 points (80-100 points) at 6 months after transplantation, and the median time of withdrawal cyclosporine, MMF and corticosteroid after transplantation was 113, 35 and 116 days respectively. The results of Kaplan-Meier method showed that the 2-year accumulative and 3-year probability of OS, LFS and GRFS of patients were all 72%. The mortality related to transplantation was 14.2%. The related factors affecting OS were the time of granulocyte implantation after transplantation (r=-0.70, P < 0.05), and the state of the disease before transplantation (r=-0.67, P < 0.05).

UCBT is an alternative choice for high-risk acute leukaemia patients who lack other source of stem cells. Patients with high implantation rate, low GVHD and relapase incidence and high GFRS can stop taking immunosuppressant in the early stage after transplantation, which can improve the quality of long-term survival of patients.