白血病患儿接受父/母单倍相合未去T细胞骨髓移植的临床观察

Clinical Investigation on Treatment of Children Leukemia with Non-T-cell Depleted Haploidentical Bone Marrow Transplantation

为探讨单倍相合未去T细胞的骨髓移植治疗儿童白血病的临床疗效及可行性,对8例白血病儿童(1.9岁-9岁)接受父/母单倍体相合骨髓移植疗效进行了评价。对5例患儿采用了含全身照射(TBI)的预处理方案,它包括阿糖胞苷+环磷酰胺+全身照射(Ara-C/CTX/TBI);对另外3例不加TBI,单用马利兰+阿糖胞苷+环磷酰胺(Bu/Ara-C/CY)预处理方案。移植物抗宿主病(GVHD)的预防措施包括供者用粒细胞集落刺激因子(G-CSF)及受者接受环孢菌素A(CsA)、氨甲蝶呤(MTX)、抗胸腺细胞球蛋白(ATG)、CD25单克隆抗体和霉酚酸酯(MMF)联合治疗。结果显示:8例患者移植后均获得造血重建,中性粒细胞数大于0.5×109/L的平均天数是16天,血小板数大于20×109/L的平均天数是17天,骨髓植活的直接证据检测证实为完全供者造血。移植后急性重度GVHD的发生率低,仅1例发生急性肠道Ⅱ-Ⅲ度GVHD(1/8);5例出现慢性GVHD,其中4例为局限性慢性GVHD,1例为泛发性(合并有肺部GVHD)。在180天内无移植相关死亡,期间无致死性严重感染发生,髓系造血和免疫功能恢复较快。中位随访33个月(范围7-56月),2例死亡,均死于白血病复发,其中1例移植后22月死于供者源复发。结论:对儿童白血病进行单倍相合未去T细胞骨髓移植时采用上述预处理方案和GVHD预防措施是安全、可行、有效的。

To investigate the efficacy and feasibility of parent non-T cell depleted haploidentical bone marrow transplants （haploidenfical BMT） for children with leukemia, the efficacy of haploidenfical BMT was evaluated in 8 leukenia children （1.9-9 years） received hematopoietic stem cell transplantation, donors were their parents with HLA-mismatched for two or three loci. Five children were pre-conditioned with a myeloablafive regimen consisting of high-dose cytarabine （Ara-C）, cyclosphosphamide （CY） and total body irradiation. Busulfan （BU）, Ara-C and CY were used for preconditioning regimen in other three children. The donors were given G-CSF prior to marrow harvest and the non-T-cell depleted grafts were used. A combination of CsA, MTX, ATG, mycophenolate mofetil （MMF） and CD25 monoclonal antibody were used for GVHD prophylaxis. The results showed that rapid engraftment was observed in all cases after transplantation by cytogenetic evidence. The mean time of neutrophil count exceeded 0.5 × 10^9/L and the mean time of platelet count exc, eeded 20 × 10^9/L were 16 and 17 days after transplantation respectively. Incidence of lethal aGVHD was lower, Ⅱ - Ⅲ acute aGVHD was found only in one out of eight patients. Chronic GVHD was observed in five patients, 4 from which showed local cGVHD, one developed extensive cGVHD. During the follow-up of 33 months （range 7 -56 months） , two patients died from relapsed leukemia, including one relapsed as donor-origin leukemia. Disease-free survival was achieved in the remaining six patients. No death occured during the follow-up of 6 months. It is concluded that above-mentioned preconditioning regimen and GVHD prophylaxis procedure in non-T-cell depleted bone marrow transplantation from HI.A-mismatched parents are effective approaches and safe strategy for the treatment of children leukemia.