人类白细胞抗原半相合亲缘性骨髓移植联合中药治疗白血病的临床观察

Effects of Combined Therapy of Human Leucocyte Antigen Haploidentical Related Bone Marrow Transplantation and Chinese Medicine in Treating Leukaemia

目的探索半相合未去除T细胞骨髓移植联合中药治疗白血病的可行性.方法4例慢性粒细胞白血病和4例急性髓性白血病患者接受人类白细胞抗原（HLA）1-3个位点不相合骨髓移植,用阿糖胞苷、环磷酰胺和全身照射或马利兰进行预处理.供者每天应用粒细胞集落刺激因子（G-CSF）250μg,连用7天后采髓.移植物抗宿主病（GVHD）预防除用环孢霉素A（CSA）和甲氨喋呤（MTX）外,在移植前4天至前1天每天用抗胸腺细胞球蛋白（ATG）2.5mg/kg,移植后第7天开始每天加用骁悉（霉酚酸酯）1.0g,骨髓输入后采用益气养阴、健脾和胃等中药治疗.结果患者移植后均获得造血重建,中性粒细胞＞0.5×10^9/L和血小板＞20×10^9/L的中位时间分别是12天（10～14天）和20天（18～25天）.8例中7例有程度不一的皮肤GVHD,其中1例为Ⅳ度皮肤GVHD,2例并发Ⅳ度急性肠道GVHD,1例在81天合并感染死亡,1例在46天自动出院,2例出现出血性膀胱炎;中位随访时间18个月（2～32个月）,无病存活6例.结论供者应用G-CSF后采髓,多种免疫抑制剂联合中药治疗HLA不全相合未去除T细胞骨髓移植,在治疗白血病过程中,有效的降低了急性重症GVHD发生,提高了无病生存率.

Objective To explore the feasibility of human leucocyte antigen （HLA） haploidentical related T-cell undepleted allogeneic bone marrow transplantation （Allo-BMT） combined with Chinese medicine for the treatment of leukaemia. Methods Four patients with chronic myeloblastic leukemia （CML） and 4 with acute myeloid leukemia （AML） received allo-BMT with graft from 1 - 3 HLA-mismatched related donors. All patients were pre-treated with standardized conditioning regimen consisting of high dose Ara-c, cyclophosphamide （CY） and total body irradiation （TBI） or busulfan. Donors were given G-CSF 250 μg/d for 7 days prior to marrow harvest. To prevent GVHD, besides application of CSA and MTX, ATG 2.5 mg/kg was given everyday for 4 days before transplantation, and MMF 1.0 g per day starting from the 7th day after transplantation. Chinese medicine for replenishing qi and yin and strengthening Pi and Wei was administrated orally after transplantation. Results Successful haematopoietic reconstruction was seen in all patients. The median days for reaching of granulocyte 〉0.5 × 10^9/L and platelet 〉20 × 10^9/L were 12 （range 10- 14） and 20 （range 18 -25） days respectively. GVHD of skin in various grade was seen in 7 patients, among whom only one advanced to grade Ⅳ ; besides, 2 accompanied with GVHD of gut, one with hemorrhagic cystitis, one died for concurrent infection on the 81st day, and one left hospital of his own accord on the 46th day. The median follow-up duration was 18 （range 2 - 32） months, during this period six patients were alive in a disease-free situation. Conclusion Combined therapy of HLA haploidentical related T-cell undepleted Allo-BMT and Chinese medicine plus immunosuppressants with pre-harvest G-CSF application in doner could effectively reduce the incidence of acute severe GVHD and raise the disease-free survival rate in treating leukaemia.