G-CSF预处理供者的HLA相合同胞异基因骨髓移植治疗慢性粒细胞白血病研究(英文)

Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia Using HLA Identical Sibling Donors Primed with G-CSF

为了评价供者应用G-CSF的骨髓移植治疗慢性粒细胞白血病的临床疗效,用HLA相合的、混合淋巴细胞培养阴性的同胞供者骨髓,对单一病种慢性粒细胞白血病行移植治疗.供者应用G-CSF 250微克/天,连用7天后供髓的32例为研究组,对照组18例常规采髓移植,在预处理方案,GVHD预防和支持治疗方法相同的情况下,比较研究组和对照组移植后在加速造血重建,降低GVHD发生和延长无病生存的疗效.移植结果显示,供者应用G-CSF在慢性粒细胞白血病移植中造血重建加速,中性粒细胞＞0.5×109/L和血小板＞20×109/L的中位天数分别是第15(10-22)天和第17.5(13-28)天,对照组是第21和24天(P＜0.01),研究组发生急性Ⅱ-Ⅳ度GVHD2例(6.3%),对照组5例(27.8%),通过比较,两组差异有显著性(P＜0.05),慢性GVHD发生分别是24%和33.3%(P＞0.05).研究组移植相关死亡、复发和无病生存与对照组比较无统计学差异(P＞0.05).结论:使用G-CSF动员供者的HLA相合的异基因骨髓移植,造血重建加快和重度急性Ⅱ-Ⅳ度GVHD减轻,有可能提高CML移植的无病生存率.

Many studies have shown that G-CSF mobilized peripheral blood progenitor cell transplants (PBPCT) manifests faster recovery kinetics than conventional bone marrow transplants.This potential advantage of PBPCT still needs to be balanced against the risk of acute and chronic GVHD associating with the infusion of 10-15 fold higher donor lymphocyte number in nnmanipulated allogeneic PBPCT than the marrow graft.To evaluate the effect of G-CSF primed bone marrow as a source of stem cells in the HLA-matched sibling transplantation,G-CSF primed with non-primed donor marrow in engraftment and incidence of GVHD for a homogenous group of patients with chronic myeloid leukemia (CML) were compared.Fifty patients with CML underwent bone marrow transplant,thirty-two donors (study group) were given G-CSF 3-4 ug/kg per day for seven days prior to marrow harvest and eighteen donors (control group) had marrow harvest without G-CSF stimulation.Conditioning regimen consisted of total body irradiation and cyclophosphamide(CY); busulfan and CY; or busulfan,total body irradiation and CY.Both groups received same post-grafting GVHD prophylaxis and post grafting G-CSF treatment.It was found that G-CSF primed donor marrow yielded with significantly higher number of total nucleated cells as well as CD34+ cells and CFU-GM compared to non-G-CSF primed marrow (P = 0.001).The median engraftment time for absolute neutrophil (ANO0.5 X lO'/L) was day 15 (range 10-22) in the group of G-CSF primed vs day 21 in the non-primed donor group (P = 0.001).The median time for platelets* >20 X 109/L) was day 17.5 (range 13-28) in the group of G-CSF primed vs day 24 in non-primed group (P = 0.001).The incidence of acute GVHD grade I-F in G-CSF primed donor group was surprisingly low,only two cases of thirty-two transplants (6.3%) with acute GVHD grade II limited to the skin.Whereas,five of eighteen patients (27.8%) in the control group developed acute GVHD grade I-IV (P = 0.032).G-CSF primed donors showed reduced CD4+ and increased CD8+ cells,resulting in a significant reduction of CD4+/CD8+ ratio as compared with non-primed marrow.The total CD3+ cell count kept unchanged in G-CSF primed donors.There were not significant differences in the incidence of the chronic GVHD (24% vs 33.3%),relapse rate (12.5% vs 11.1%) and overall survival rate (78.1% vs66.7%,P = 0.32) during 6-50 months of follow-up.In conclusion,G-CSF primed donor marrow accelerates engraftment.Although G-CSF did not change the total CD3 + cells in bone marrow,it altered the ratio of CD4+ and CD8+ cells and significantly reduced the incidence of acute GVHD.