单倍体相合骨髓移植中急性移植物抗宿主病预防新方案的临床研究

目的　探讨骨髓移植 (BMT)供者应用G CSF和受者接受连续免疫抑制剂及加CD2 5单克隆抗体 (单抗 )预防急性重度移植物抗宿主病 (GVHD)的单倍体移植方案的可行性。方法　 38例白血病患者接受单倍体相合未去T细胞BMT ,供者应用G CSF动员 7d后采集骨髓 ;受者应用连续免疫抑制剂预防急性GVHD ,临床观察移植结果。结果　所有患者均取得三系造血重建 ,移植后粒细胞 >0 .5×1 0 9 L及血小板 >2 0× 1 0 9 L的中位时间分别为第 1 9天和 2 3天 ,植入直接证据检测证实完全供者造血 ,发生Ⅱ～Ⅳ度急性GVHD 4例 ,发生率为 1 0 .5 % ,无病存活大于 6个月可评价慢性GVHD 2 8例 ,均发生慢性GVHD ,表现轻微和局限 ,其中广泛性慢性GVHD 3例 ,发生率为 1 0 .7%。免疫功能恢复的结果显示 ,在移植后 1 8个月内动态观察免疫细胞计数的变化 ,CD3+、CD8+、CD1 9+、CD56+细胞在 1 2个月内可恢复至正常水平 ,CD4+细胞在移植后 1 8个月内恢复。随访中位时间 1 2个月 (6～ 2 6个月 ) ,死亡 1 2例 ,Kaplan Meier生存分析 ,2年估计无病生存率为 (68.4± 6 .0 ) % ,存活病例Karnofsky评分大于 90 %。结论　经G CSF动员的骨髓与连续免疫抑制剂的应用 ,特别是CD2 5单抗应用于未去T细胞单倍体相合BMT急性重度GVHD的预防 ,对移植物植入、免疫

Clinical study of a new protocal for acute graft-versus host disease prophylaxia in HLA-haploidentical bone marrow transplantation(BMT)

OBJECTIVE: To explore the feasibility of a new protocol for acute graft versus host disease (aGVHD) prophylaxis in haploidentical bone marrow transplantation. METHODS: Thirty-eight high-risk leukemia patients underwent haploidentical G-CSF primed bone marrow transplantation without ex-vivo T cell depletion, the donors were given G-CSF 250 microg/d for 7 days prior to marrow harvest. All patients received a same chemo-radiation conditioning regimen, including cytarabin, cyclophosphamide and total body irradiation (TBI). GVHD prophylaxis regimen consisted of ATG, CsA, MTX, Mycophenolate mofetil (MMF) and anti-CD(25) monoclonal antibody (MoAb). RESULTS: All patients achieved engraftment of a median of 19 and 22 days for neutrophil and platelet, respectively. Cytogenetic analysis showed 100% donor hematopoietic cells in all recipients after transplantation. One of the twenty patients (5%) experienced grades II - IV acute GVHD. The recovery of CD(3)(+)CD(8)(+) T cells, CD(19)(+) cells and CD(56)(+) cells after transplantation was within 3 approximately 12 months. Of the 20 patients, 16 were alive with minimal and limited chronic GVHD and karnofsky score over 90% in a median follow-up of 9 months. Disease free survival (DFS) rates was (80 +/- 9)%. CONCLUSION: G-CSF priming marrow graft along with sequential immunosuppressants, especially the addition of anti-CD(25) MoAb for aGVHD prophylaxis could achieve excellent engraftment, proper immune reconstitution and very low incidence of grade II - IV GVHD. The new protocol is effective and feasible in preventing severe acute GVHD and improving DFS.