Barber W H, Mankin J A, Laskow D A, Deierhoi M H, Julian B A, Curtis J J, Diethelm A G
Department of Surgery, University of Alabama School of Medicine, Birmingham 35294.
Transplantation. 1991 Jan;51(1):70-5. doi: 10.1097/00007890-199101000-00011.
Experimental studies have shown that antilymphocyte globulin combined with transfusion of donor-specific bone marrow cells can induce partial tolerance to allograft tissue. We have adapted these protocols to clinical use and present the results of 57 cadaveric renal allograft recipients who received Minnesota ALG followed by the transfusion of cryopreserved donor-specific bone marrow. A group of 54 patients received the contralateral kidney and similar immunosuppression without the marrow transfusion and serve as controls. Both groups received quadruple immunosuppression with MALG, cyclosporin, azathioprine, and prednisone. In the bone marrow group, after a 10-14 day induction course of ALG, cryopreserved marrow was transfused on the seventh day after the last dose of ALG. The median follow-up in both groups is 16 months, (range 2.5-33 months). Six grafts have been lost in the bone marrow group, (three rejections, 2 deaths [Cr 2.0, 2.3], 1 recurrent disease). In the control group 16 grafts have been lost (13 rejections, 3 deaths [Cr 1.7, 2.5, 3.0]). Five patients in the control group have biopsy-proved chronic rejection compared to one in the bone marrow group. 17 patients in the bone marrow group have been tapered off the prednisone, and three of these patients have had mild late rejection episodes without graft loss. The two groups were compared for differences in the number of rejection episodes, estimated renal plasma flow, glomerular filtration rate, and urine protein. No differences were found. The allograft survival of the bone marrow group was significantly greater (P less than .01) than the control group. The graft survival rates for the bone marrow group at 12 and 18 months were 90% (confidence limits [CL] 85-94) and 85% (CL 78-90), respectively. In the the control group the 12 and 18 month allograft survival rates were 71% (CL 63-78) and 67% (CL 58-74), respectively. The survival in the control group was similar to our overall transplant experience with quadruple therapy. Mixed lymphocyte culture analysis shows a trend to diminished donor-specific responsiveness in the bone marrow group. The use of cryopreserved donor-specific bone marrow is associated with improved allograft survival in cadaveric kidney allograft recipients. However, a more effective induction protocol is needed to reduce the overall number of rejection episodes.
实验研究表明，抗淋巴细胞球蛋白与输注供体特异性骨髓细胞相结合，可诱导对同种异体移植组织产生部分耐受性。我们已将这些方案应用于临床，并呈现了57例尸体肾移植受者的结果，这些受者接受了明尼苏达抗淋巴细胞球蛋白（Minnesota ALG）治疗，随后输注了冷冻保存的供体特异性骨髓。一组54例患者接受了对侧肾脏移植，并接受了类似的免疫抑制治疗，但未进行骨髓输注，作为对照组。两组均接受了MALG、环孢素、硫唑嘌呤和泼尼松的四联免疫抑制治疗。在骨髓组中，经过10 - 14天的ALG诱导疗程后，在最后一剂ALG后的第7天输注冷冻保存的骨髓。两组的中位随访时间为16个月（范围2.5 - 33个月）。骨髓组中有6个移植物丢失（3例排斥反应，2例死亡[肌酐2.0, 2.3]，1例复发性疾病）。对照组中有16个移植物丢失（13例排斥反应，3例死亡[肌酐1.7, 2.5, 3.0]）。对照组中有5例患者经活检证实为慢性排斥反应，而骨髓组中有1例。骨髓组中有17例患者逐渐减少了泼尼松的用量，其中3例患者出现了轻度的晚期排斥反应，但移植物未丢失。比较两组在排斥反应发作次数、估计肾血浆流量、肾小球滤过率和尿蛋白方面的差异，未发现差异。骨髓组的同种异体移植物存活率显著高于对照组（P小于0.01）。骨髓组在12个月和18个月时的移植物存活率分别为90%（置信区间[CL] 85 - 94）和85%（CL 78 - 90）。对照组在12个月和18个月时的同种异体移植物存活率分别为71%（CL 63 - 78）和67%（CL 58 - 74）。对照组的存活率与我们采用四联疗法的总体移植经验相似。混合淋巴细胞培养分析显示骨髓组中供体特异性反应性有降低的趋势。在尸体肾移植受者中，使用冷冻保存的供体特异性骨髓与改善同种异体移植物存活率相关。然而，需要一种更有效的诱导方案来减少排斥反应发作的总数。
