抗CD25抗体预防移植物抗宿主病在儿童白血病半匹配骨髓移植中的应用

CD25 monoclonal antibody for GVHD prophylaxis in non-T-cell depleted haploidentical bone marrow transplantation for treatment of children leukemia

目的 探讨抗 CD2 5抗体用于预防儿童白血病半匹配未去 T细胞骨髓移植重度移植物抗宿主病 (GVHD)的疗效。 方法 10例儿童白血病患者接受 HL A2 - 3位点不合半匹配骨髓移植 ,移植方法除了供者应用粒细胞集落刺激因子 (GCSF)2 5 0μg促进骨髓及受者应用环孢素 A(CSA ) ,甲氨蝶呤 (MTX) ,抗胸腺细胞球蛋白 (ATG)和霉酚酸酯 (MMF)预防 GVHD综合措施外 ,加用抗 CD2 5单克隆抗体预防 GVHD,剂量各为 2 0 m g,在移植前 2 h和移植后第 4天应用 ,采髓后未去 T细胞输注 ,移植结果与前期未用 Simulect移植组比较。 结果 10例移植后均获造血重建 ,粒细胞大于 0 .5× 10 9/ L 中位天数是19 d,血小板大于 2 0× 10 9/ L 的中位天数是 2 2 d,骨髓植活直接证据检测证实为完全供者造血。无 1例发生急性 ～ GVHD,未用 Sim ulect对照组急性 ～ GVHD为 5 0 % ,差异有显著性意义。可评价慢性 GVHD的 8例均发生慢性 GVHD,均为局限性慢性 GVHD。中位随访 12个月 (范围 9～ 2 4个月 ) ,2例移植相关死亡 ,1例移植后 14个月复发死亡 ,实际无病生存率是 70 % ,与对照比较差异无显著性意义。 结论 本研究儿童半匹配未去 T细胞骨髓移植应用 Sim ulect,明显降低急性重症 a GVHD发生 ,减少移植相关死亡 ,临床应用安全可行。

Objective To explore the effects of CD25 monoclonal antibody on reducing the incidence of severe acute GVHD in haploidentical bone marrow transplantation for treatment of children leukemia. Methods Ten children patients with leukemia received haplotype Allo BMT from HLA two or three loci mismatched related donor.Most patients classified as high risk category. The donors of patients were given G CSF (Lenograstim Chugai) 250 μg/day for seven doses prior to marrow harvest. In addition to combination of CSA?MTX ?ATG and Mycophenolate mofetil (MMF) for GVHD prophylaxis, CD25 monoclonal antibody (Simulect,Novartis Pharma Switzerland) was administered to prevent acute severe GVHD.A totoal 40 mg Simulect was given in two doses of 20mg each by 30 min intravenous infusion on 2 h before transplantation and day 4 after transplantation. The outcomes were compared with those of historical 8 children patients with leukemia who received haploidentical bone marrow transplantation without CD25 antibody for GVHD prophylaxis. Results All patients were engrafted and sustained full donor type engraftment. 100% donors hematopoietic cells after transplantation was determined by cytogenetic evidence analysis .The median days of granulocyte exceeding 0.5×10 9/L and pallets exceeding 20×10 9/L were 19 and 22 days.Patients were monitored up to days 100 for the sign of aGVHD.None developed the Ⅱ Ⅳacute GVHD. However,the incidence of the Ⅱ Ⅳ acute GVHD in control group was 50%(P<0.05). Eight patients could be evaluated for chronic GVHD.All experienced chronic GVHD confined to the skin. The median follow up duration was 12 months (range 9～24 months) .Two patients died from transplant related mortality,one patient relapsed and died. The remaining seven patients were alive in disease free situation. Conclusion The use of Simulect in haploidentical bone marrow transplantation for treatment of children patients with leukemia is effective on preventing acute severe GVHD and may be reduced transplant related mortality.