强化清髓性非血缘脐带血造血干细胞移植治疗急性淋巴细胞白血病的疗效观察

The curative efficacy of unrelated umbilical cord blood stem cells transplantation in intensified myeloablative conditioned patients with acute lymphoblastic leukemia

目的 回顾性分析采用强化清髓性预处理方案的非血缘脐带血造血干细胞移植（UCBT）治疗急性淋巴细胞白血病（ALL）的疗效.方法 2006年9月至2013年12月安徽医科大学附属省立医院共110例ALL患者进行了清髓性预处理的UCBT,其中男79例,女31例.中位年龄14（2 ～51）岁,中位体重45（12 ～100）kg.在第1次完全缓解（CRl）后进行移植者61例,在CR2、CR3以上及疾病进展期进行移植者分别有30、6和l3例.预处理方案采用全身照射/环磷酰胺/阿糖胞苷（TBI/Cy/Ara-C） 61例,白消安/环磷酰胺/氟达拉滨（BU/Cy/Flu） 39例,BU/Cy/Ara-C 10例.移植物抗宿主病（GVHD）预防采用环孢素A联合霉酚酸酯方案.结果 所有患者输入复温后脐血,总有核细胞数中位数为3.90（1.97 ～13.50）×10^7/kg,CD34＋细胞中位数为2.07（0.40 ～5.56）×10^5/kg.中性粒细胞累积植入率为94.5％ （95％ CI 94.5％ ～94.6％）,植入的中位时间为18（12 ～37）d.移植后180 d血小板累积植入率为82.1％ （95％CI81.8％ ～ 82.4％）,血小板植入的中位时间为40（15 ～153）d.Ⅱ～Ⅳ度急性GVHD和Ⅲ～Ⅳ度急性GVHD发生率分别为21.8％和10.9％.慢性GVHD的发生率为17.9％.中位随访时间26（6 ～94）个月,3年无病生存率和总生存率分别为54.5％和56.4％.180 d移植相关死亡率为22.7％ （95％ CI 22.4％ ～ 23.0％）.3年累积复发率为18.3％（95％ CI 17.9％～18.6％）.结论 强化清髓性预处理方案的UCBT应用于儿童及成人ALL的治疗提高了UCBT的植入率,而且缩短了中性粒细胞及血小板植入的时间.对于有移植适应证而又缺少HLA相合同胞供者的患者是一种安全、有效的治疗选择.

Objective To retrospectively analyze the efficacy of unrelated umbilical cord blood transplantation （UCBT） with intensified myeloablative conditioning regimen in patients with acute lymphoblastic leukemia （ALL）.Methods From September 2006 to December 2013,a total of 110 consecutive patients with ALL had received UCBT,including 79 male and 31 female patients with a median age of 14（2-51） years,a median weight of 45 （12-100）kg.Sixty-one cases were in the first complete remission （CR）,30,6 and 13 patients in the second,the third CR and advanced stages respectively.The conditioning regimen consisted of total body irradiation,cyclophosphamide and cytarabine （TBI/Cy/Ara-C） in 61 patients,busulfan,cyclophosphamide and fludarabine （BU/Cy/Flu） in 39 patients and BU/Cy/Ara-C in 10 patients.All patients received a combination of cyclosporine （CsA） and mycophenolate mofetil （MMF） for the prophylaxis of graft-versus-host disease （GVHD）.Results The median amount of total nuclear cells（TNC） and CD34＋ cells were 3.90（1.97-13.50） × 10^7/kg and 2.07 （0.40-5.56） × 10^5/kg.The cumulative incidence of sustained donor engraftment was 94.5% （95% CI 94.5%-94.6%） at a median of 18 days after transplantation （range,12-37 days）.The cumulative incidence of platelet recovery at 180 days after transplantation was 82.1% （95% CI 81.8%-82.4%） with a median time to recovery of 40 （range,15-153） days.Incidences of grade Ⅱ ～ Ⅳ and Ⅲ ～ Ⅳ acute GVHD were 21.8% and 10.9% respectively.The cumulative incidence of chronic GVHD was 17.9%.During a median follow up period of 26 （range 6-94） months,the disease free survival （DFS） and overall survival （OS） rates at 3 years were 54.5% and 58.8%,respectively.The transplantation-related mortality （TRM） at 180 days after transplantation was 22.7 %.The cumulative incidence of 3-year relapse rate was 18.3 % （95 % CI 17.9%-18.6%）.Conclusions UCBT with intensified myeloablative conditioning regimen not only improves the donor engraftment,but also shortens the interval of neutrophil and platelet recovery.It is a safe and effective option for children and adult ALL patients lack of matched related donors.