外周血联合脐血模式单倍体异基因造血干细胞移植治疗恶性血液病

HLA-haploidentical peripheral blood hematopoietic cell transplantation in combination with third-party umbilical cord blood transfusion for hematologic malignancies

目的探讨外周血联合脐带血模式单倍体异基因造血干细胞移植(allo-HSCT)的疗效及不同年龄受者术后并发症发生情况及存活情况。方法2014年1月至2017年12月31日接受外周血联合脐带血模式单倍体allo-HSCT受者50例,其中男性39例,女性11例,中位年龄为35岁(9~67岁)。将受者按照年龄分为三组,A组(17例):年龄<30岁;B组(19例):年龄为30~49岁;C组(14例):年龄≥50岁,移植前评估疾病均未缓解。移植时(当天上午),首先输注1份第三方脐带血以减少移植后GVHD的发生,然后(当天下午)输注造血干细胞。移植后所有受者均采用兔抗人胸腺细胞免疫球蛋白(ATG)+环孢素A+短程甲氨蝶呤(MTX)预防移植物抗宿主病(GVHD)。结果植入前2例受者死于感染,4例(8.0%)受者植入失败,其余受者中性粒细胞(ANC) >0.5×10^9/L的中位时间为14d(10~22d),血小板计数 >20×10^9/L的中位时间为20d(11~186d)。植入受者的完全供者嵌合的中位时间为28d(14~42d)。A组中有1例(5.9%)植入失败,B组有2例(10.5%),C组有1例(7.1%),差异均无统计学意义(χ^2=0.282,P=0.868)。中位随访时间7.2个月(0.4~27.2个月),50例受者中,12例(24%)发生Ⅱ~Ⅳ度的急性GVHD(aGVHD),其中A组6例(35.3%),B组5例(26.3%),C组1例(7.1%),3组间Ⅱ~Ⅳ度aGVHD发生率的比较,差异均无统计学意义(χ^2=3.624,P=0.180)。29例(58%)受者移植后发生过病毒感染。A组及B组各1例受者出现原发病复发,C组无复发。21例(42%)受者死亡,29例(58%)受者存活。预计移植后2年总体存活率(OS)为60.2%。C组移植后2年OS为77.1%。结论外周血联合脐带血单倍体allo-HSCT疗效良好;在 >50岁的未缓解高危受者中,采用适合的预处理方案不增加移植后aGVHD和病毒感染的发生率,并延长存活时间。

Objective To evaluate the efficacy of peripheral blood combined with cord blood model for haplo-hematopoietic stem cell transplantation and the occurrence,survival of complications in patients of different ages.Methods From January 2014 to December 31,2017,there were 50 patients undergoing haploid allogeneic hematopoietic stem cell transplantation in our department.There were 39 males and 11 females.The median age was 35 (9-67) years.The stratification was divided into 3 groups.In group A,17 patients were younger than 30 years old;in group B,19 patients were between 30 and 49 years old,and in group C,14 patients were not less than 50 years.No remission was assessed before transplantation in this group.On the morning of the reinfusion,the selection of a third-party umbilical cord blood for transfusion reduced the occurrence of GVHD.Peripheral blood was infusion in the afternoon.All patients were treated with ATG+ CSA + short-term MTX to prevent GVHD.Results Two patients died of infection prior to graft,4 (8.0%) patients were graft failure.The median time of ANC≥0.5×10^9/L (range) and platelet ≥20×10^9/L(range) in the other patients were 14d(10-22 d) and 20(11-186) d,individually.The median time of full donor chimerism(range)was 28d(14-42 d).Graft failure was occurred in one case (5.9%),two cases (10.5%) and one case (7.1%) in each group,with no statistically significant difference (χ^2=0.282,P=0.868).With a median follow-up of 7.2 months (0.4-27.2 months),12 (24%) had aGVHD of II-IV degrees,among them,6 cases (35.3%) in group A,5 cases (26.3%) in group B,1 case (7.1%) in group C had aGVHD of II-IV degrees.There was no significant in the incidence of aGVHD in three groups (χ^2=3.624,P=0.180).Twenty-nine (58%) patients had viral infections after transplantation.One patient in both group A and B relapsed,and there was no recurrence in group C.21 (42%) patients died and 29 (58%) patients survived.The predicted 2-year overall survival (OS) was 60.2%.In group C,the 2-year overall survival (OS) was 77.1%.Conclusion The haploidentical hematopoietic cell transplantation model of peripheral blood combined with third-party umbilical cord blood transfusion has a good outcome and prolonged survival time in high-risk elder patients.The use of suitable conditioning regimens did not increase the incidence of aGVHD and virus infection.