非亲缘异基因外周血干细胞移植重建白血病幼儿造血功能:1例报告

Reconstruction of haematogenous function in a leukemic child following unrelated donor allogeneic peripheral blood stem cell transplantation:A case report

目的:分析非亲缘异基因外周血干细胞移植治疗幼儿急性非淋巴性白血病的可行性。方法:患儿,男,3岁,于2005-07-18为行造血干细胞移植入本院血液科骨髓移植病房,入院诊断为急性非淋巴细胞性白血病-M5b。经抗肿瘤药物治疗病情获得完全缓解。患儿首先接受清髓性预处理,然后接受同性别非亲缘异基因外周血造血干细胞移植。①移植预处理包括马利兰、阿糖胞苷和环磷酰胺。移植前依次用药为马利兰3.2mg/(kg·d)×4d,口服,于移植前6,7,8,9d给药;阿糖胞苷3.2g/(m2·d)×2d,于移植前4,5d给药;环磷酰胺54mg/(kg·d),于移植前2,3d给药。②急性移植物抗宿主病的预防用药包括环孢菌素A和氨甲蝶呤、抗胸腺细胞球蛋白及吗替麦考酚酯。供者接受粒细胞集落刺激因子动员4d后采集外周血造血干细胞,供、受者间HLA全相合,患者血型A,供者血型B,主次要均不合。结果:①患儿移植后早期获得造血重建,中性粒细胞>0.5×109L-1和血小板>50×109L-1的天数分别是12d和11d。②移植后1个月经DNA短串联重复序列多态性分析证明为供者型完全植入,移植后3个月查骨髓象正常。③移植后3,6个月定期行淋巴细胞亚群检查表明除CD19+,CD4+细胞未恢复外,自然杀伤细胞在移植后3个月恢复正常,T淋巴细胞CD3+与CD8+、体液免疫球蛋白在移植后6个月中均获得重建。④整个移植过程顺利,未出现明显感染和重度急性移植物抗宿主病。移植后96d时出现Ⅰ度皮肤移植物抗宿主病,经加用激素治疗,皮疹消失。移植术后已随访观察12个月,患儿正常生活。结论:如果患儿有HLA完全相合的供者,非亲缘异基因外周血干细胞移植治疗儿童高危白血病是一种有效和安全的方法,对国内独生子女家庭拓宽供者来源有重要的实用价值。

AIM：To analyze the feasibility of unrelated donor allogeneic peripheral blood stem coil transplantation （URD-PBSCT） for childhood＇s acute non-lymphatic leukemia. METHODS： A three-year-old boy, who were diagnosed as having acute non-lymphocytic leukemia M5b and would receive hematopoietic stem cell transplantation （HSCT）, hospitalized in the Bone Marrow Transplant Ward, Department of Hematology, General Hospital of Air Force on July 18^th, 2005. His condition was fully remised after antitumor drug treatment. Firstly, the child patient received non-myeloablative pretreatment, and then received URD-PBSCT of the same sex. （1）The transplantation pre-treatment contained busufanum （BU）, cytarabine and cyclophosphamide （CY）. The drug was given in order, which was BU 3.2 mg/kg per day for 4 days, taken orally, at days 6, 7, 8 and 9 before transplantation, cytarabine 3.2 g/m^2 per day for 2 days, at days 4 and 5 before transplantation, CY 54 mg/kg per day, at days 2 and 3 before transplantation. （2）Cyclosporine （CSA）, methotrexate （MTX）, antithymocyte globulin （ATG） and mycophenolate mofetil （MMF） were used for graft-versus-host disease （GVHD） prophylaxis. For 4 days before the peripheral blood stem cell harvest the donor was given granulocyte colony-stimulating factor （G-CSF）. The donor and recipient was all match for human leukocyte antigen （HI_A）, but blood type was different, A in the patient and B in the donor. RESULTS： （1）The child patient received haematogenous reconstruction in an early pedod after transplantation. The duration when granulocyte exceeded 0.5×10^9 L^-1 was 12 days and platelet exceeded 50×10^9 L^-1 was 11 days. GOne month after transplantation the DNA short tandem repeat （STR） sequence polymorphism analysis certificated that the donor was implanted fully, and at month 3 after transplantation the bone marrow was normal. （3）At months 3 and 6 after transplantation, the routine subgroup of leukomonocytes examine showed that except the CD19^＋ and CD4^＋ cell, natural killer cells recovered to normal at month 3 after transplantation. T leukomonocyte CD3^＋ and CD8^＋ and humor immune globulin were reconstructed during the 6 months after transplantation. （4）The course of transplantation was all right, and there was no evidence of severe infection and severe GVHD. Grade I skin GVHD occurred at day 96. Erythra disappeared after hormonal therapy. This child was normal alive for more than 12 months follow-up after transplantation. CONCLUSION： URD-PBSCT is an effective and safe method for childhood＇s high-risk leukemia if the child patient has a HLA completely matched donor. It is important to spread donor source for domestic only-child family.