非清髓性同种造血干细胞移植治疗恶性实体瘤13例

Effect of Nonmyeloblative Preconditioning AUogeneic Hematopoietic Stem Cell Transplantation on Malignant Solid Tumor

目的:探讨非清髓性同种外周血造血干细胞移植治疗复发及难治性实体瘤的疗效及安全性,并研究移植物抗肿瘤效应(GVT)产生的抗肿瘤免疫效果。方法:13例患者,其中原发不明癌5例,其他经手术,放、化疗治疗后复发及多部位转移,难治性实体瘤8例。年龄17～69岁,中位年龄45岁。ECOG分级:0级5例,1级6例,2、3级各1例。全部患者给予非清髓性预处理方案进行同种外周血造血干细胞移植。供者为HLA完全相合者10例,非血缘关系者3例。ABO血型相合9例,不相合者4例。采集CD34^+数为1.4～6.6×10~6/kg,平均为3.46×10~6/kg。预处理方案三种:供者为同胞的患者采用环磷酰胺+氟达拉宾方案;非血缘供者患者采用氟达拉宾+马法兰方案。移植物抗宿主病(GVHD)防治采用环孢素A或加用甲氨蝶呤。疗效判定以治疗前后肿瘤大小做为移植物抗肿瘤(GVT)效果判定。同时观察同种造血干细胞移植的副作用。结果:全部患者均获造血重建,移植后中性粒细胞>0.5×10~9/L平均时间11.9天,血小板>20×10~9/L平均时间14.9天,不良反应主要表现为胃肠道、皮肤黏膜及神经系统。急性GVHD9例,经治疗后好转。慢性GVHD8例,均为广泛型。GVT效应:1例GVT+++,肿瘤完全消失,无瘤生存887天。3例GVT++,无瘤生存334天。5例GVT+,无瘤生存117～203天。移植效果:以持续3个月以上统计,CR1例,PR2例,SD4例,PD5例,移植相关死亡1例。总有效率为53.8%。不良反应:主要为急性GVHD,表现为胃肠道反应如腹泻,感染等,肝静脉血栓及脑病少见。经对症治疗好转。结论:对复发及难治性实体瘤,特别是原发不明癌采用非清髓性同种外周血造血干细胞移植可提高疗效,并通过移植物抗肿瘤效应使瘤体减小,延长患者生存期、本疗法具有较好的安全性。

Objective： To evaluate the safety and efficacy of nonmyeloablative preconditioning allogeneic hematopoietic stem cell transplantation （NMHSCT） in the therapy of unidentified relapse and primary solid tumors, and to study the anti-tumor immunity induced by the effect of Graft-Verus-Tumor （GVT）. Methods： A total of 13 difficult-to-treat cancer patients received NMSCT and the efficacy and side effects were observed. Results： One case had CR, 2 cases had PR, 4 cases had SD, 5 cases had PD, and 1 case died of complications associated with transplantation. One case was GVT （＋＋＋）, 3 cases were GVT （＋＋）, 5 cases were GVT（＋）, and 4 cases were GVT （-）. The main side effect was acute GVHD presented as diarrhea and infection. VOD and brain disease were rare. Conclusion： Nonmyeloablative allogeneic stem cell transplantation is safe and effective for solide tumors.