环孢素A+甲氨蝶呤+霉酚酸酯+抗胸腺细胞球蛋白四联方案预防无关供体造血干细胞移植中的移植物抗宿主病

目的评价环孢素A(CsA) 甲氨蝶呤(MTX) 霉酚酸酯(MMF)和低剂量抗胸腺细胞球蛋白(ATG)预防无关供体造血干细胞移植(URD-HSCT)中移植物抗宿主病(GVHD)的疗效。方法13与11例白血病患者分别接受URD-HSCT和相关供体(RD)-HSCT。移植预处理方案:19例应用全身放疗 环磷酰胺方案、5例应用改良BuCY(羟基脲、马利兰、阿糖胞苷、环磷酰胺)方案;无关移植病人供体与受体之间HLA-A、B、DR基因位点完全相合11例,1个基因位点不合2例。所有相关移植病人供体与受体之间血清学位点均为全相合;预防GVHD方案:所有病人均接受CsA MTX方案,行URD-HSCT病人在CsA MTX方案基础上加用MMF和ATG。结果移植后所有患者均获得造血重建,移植中预处理相关毒性(RRT)发生率和程度在无关与相关移植中二者无差异(P>0.05);急性GVHD(aGVHD)在无关与相关移植病人分别为46.2%和55.6%,在可统计的慢性GVHD(cGVHD)病人中,无关移植是4/7例,相关移植6/9例;无关与相关移植病人中分别有1例死于移植相关并发症,移植后1年估计无病生存率在无关与相关移植分别为87.5%和90.9%;移植后巨细胞病毒(CMV)抗原阳性率在无关与相关移植无差异(P>0.05)。结论CsA MTX MMF ATG四联方案预防URD-HSCT中GVHD能降低aGVHD的发生及其程度,不增加移植后相关死亡率和CMV感染率。

Quadruple therapy with CsA, MTX, MMF and ATG for preventing graft-versus-host disease in unrelated donor hematopoietic stem cell transplantation

Objective To evaluate the efficacy of quadruple therapy with cyclosporine (CsA), methotrexate (MTX), mycophenolate mofetil (MMF) and low-dose antithymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis in unrelated donor hematopoietic stem cell transplantation (URD-HSCT). Methods Thirteen patients with leukemia received URD-HSCT, of whom 11 had HLA genotypes and 2 had mismatch for 1 genetic locus. Another 11 leukemia patients all serologically matched underwent related donor (RD)-HSCT. Total body irradiation (TBI) plus cyclophosphamide (CTX) was adopted in 19 cases and modified BuCY conditioning regimen (hydroxyurea, busulfan, Ara-C, Cyclophosphamide ) in the other 5 cases. All the patients received CsA MTX protocal for GVHD prophylaxis, and in those undergoing URD-HSCT, additional MMF and low-dose ATG were used. Results The incidence and severity of regimen-related toxicity differed little between unrelated and related transplantation. Acute GVHD (aGVHD) occurred in 46.2% of the patients undergoing URD- HSCT and in 55.6% of those with RD-HSCT, respectively. Four patients had chronic GVHD (cGVHD), in the 7 ones who could be followed up after URD-HSCT; 6 of the 9 patients with RD-HSCT developed cGVHD postoperatively. One patient with URD-HSCT died of hemorrhagic cystitis and another with RD-HSCT died of cytomegalovirus (CMV) pneumonia. The at one-year disease-free survival rate was 87.5% and 90.9% in patients with unrelated and related transplantation respectively. Significant difference was not noted in the positivity rate of CMV antigen between the patients receiving URD-HSCT or RD-HSCT. Conclusion CsA MTX in combination with MMF and low-dose ATG may decrease the incidence and severity of aGVHD without increasing transplant-related mortality or CMV infection.