Shapiro R, Rao A S, Fontes P, Zeevi A, Jordan M, Scantlebury V P, Vivas C, Gritsch H A, Corry R J, Egidi F
Department of Surgery, Pittsburgh Transplantation Institute, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Transplantation. 1995 Dec 27;60(12):1421-5. doi: 10.1097/00007890-199560120-00009.
On the basis of observations in patients with long-term (28-30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3-5 x 10(8) unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 +/- 10.8 years, and the mean donor age was 31.8 +/- 16.1 years; the mean cold ischemia time was 23.0 +/- 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 +/- 11.7 years, and the mean donor age was 41.5 +/- 17.9 years; the mean cold ischemia time was 28.6 +/- 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 +/- 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 +/- 1.2 mg/dl and a BUN of 26 +/- 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 +/- 1.3 mg/dl, and a BUN of 30 +/- 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P = NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P < .02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P = NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.
基于对长期(28 - 30年)肾移植存活患者的观察,这些患者均有全身微嵌合体的证据,我们启动了一项肾/骨髓联合同期移植计划。在1992年12月14日至1994年10月31日期间,36例肾移植受者接受了3 - 5×10⁸个未修饰的骨髓细胞/千克;6例患者还接受了胰岛移植,7例患者还接受了胰腺移植。受者平均年龄为39.0±10.8岁,供者平均年龄为31.8±16.1岁;平均冷缺血时间为23.0±9.1小时。20例对照患者仅接受了肾脏移植,主要是因为供者家属拒绝同意获取椎体;其中3例患者还接受了胰腺移植。受者平均年龄为47.9±11.7岁,供者平均年龄为41.5±17.9岁;平均冷缺血时间为28.6±6.2小时。所有患者均接受以他克莫司为基础的治疗,未进行放疗、细胞减灭或诱导性抗淋巴细胞制剂治疗。在移植前及移植后定期采血,用于检测嵌合体及进行免疫学研究。平均随访11.1±5.8个月,36例研究患者全部存活,33例(92%)移植肾功能良好,平均血清肌酐为1.9±1.2毫克/分升,血尿素氮为26±9毫克/分升。未在任何患者中观察到移植物抗宿主病。排斥反应发生率为72%;11%的患者因激素抵抗性排斥反应需要使用OKT3或抗胸腺细胞球蛋白。巨细胞病毒(CMV)感染发生率为14%,移植肾功能延迟发生率为17%。共有18例(90%)对照患者存活,17例(85%)移植肾功能良好,平均血清肌酐为2.1±1.3毫克/分升,血尿素氮为30±13毫克/分升。排斥反应发生率为60%,10%的患者需要使用OKT3或抗胸腺细胞球蛋白。CMV感染见于15%的患者,移植肾功能延迟见于20%的患者(P = 无显著性差异)。在研究患者中,通过聚合酶链反应(PCR)或流式细胞术在31例可评估患者中的30例(97%)外周血中检测到了嵌合体。在对照患者中,14例可评估患者中的9例(64%)观察到了嵌合体(P < 0.02)。在6/29(21%)可评估的研究患者和4/14(29%)可评估的对照患者中观察到供者特异性反应性降低(P = 无显著性差异)。我们得出结论,肾/骨髓联合移植与可接受的患者及移植物存活率、嵌合体增加以及移植后早期事件无变化相关。