Trofe Jennifer, Stratta Robert J, Egidi M Francesca, Lo Agnes, Gaber Lillian W, Shokouh-Amiri M Hosein, Grewal Hani P, Honaker Marsha, Hardinger Karen, Alloway Rita R, Gaber A Osama
Department of Pharmacy, University of Tennessee-Memphis, Memphis, TN, USA.
Clin Transplant. 2002;16 Suppl 7:34-44. doi: 10.1034/j.1399-0012.16.s7.5.x.
To review the safety and efficacy of thymoglobulin in pancreas transplant patients receiving tacrolimus and mycophenolate mofetil.
Retrospective, single centre analysis of 45 patients transplanted between 1995 and 2000 who received 54 courses of thymoglobulin, including 36 courses in 29 solitary pancreas transplant recipients (16 pancreas alone, 13 pancreas after kidney transplants) and 18 courses in 16 simultaneous kidney-pancreas transplant patients. Thirty-two patients (71%) were primary pancreas transplants, 10 (22%) were second transplants and three (7%) were third transplants. Of the 54 treatment courses, 19 (35%) were for induction, 27 (50%) were for primary rejection and eight (15%) were rescue therapy for rejection. All rejection episodes were biopsy-proven in at least one organ.
The median thymoglobulin dose was 1.5 mg/kg/d with a mean of six doses (range 3-10). Dose reduction or interruption was required in 28 courses (52%), most often due to leukopenia (n = 24), fever (n = 2) and thrombocytopenia (n = 2). Thymoglobulin was resumed in all but three patients, two with persistent fever and one with infection. Infectious complications (n = 25) occurred in 17 patients (38%) within 30 days and included bacterial (n = 16), cytomegalovirus (n = 4), polyoma (n = 1), fungal (Candida albicans, n = 1), toxoplasmosis (n = 1) and ehrlichiosis (n = 2). Post-transplant lymphoproliferative disease occurred in two patients (4%) at a mean of 70 d post-thymoglobulin treatment. In the 19 patients that received thymoglobulin induction, one simultaneous kidney-pancreas transplant, two pancreas alone and four pancreas after kidney transplant recipients developed rejection (37% incidence), while all remaining patients followed by surveillance protocol biopsies were rejection-free. In the 35 patients that received thymoglobulin for rejection, reversal occurred in 26 of the patients (74%). Rejection recurred within 30 d in five patients and post-treatment biopsies revealed persistent rejection in three of 20 pancreas and two of eight renal biopsies. After a mean follow-up of 6 months, the actual patient and pancreas graft survival rates were 93% and 71%, respectively.
Thymoglobulin was effective as induction therapy in high-risk pancreas transplant recipients, and resulted in initial reversal of rejection in 74% of patients. Dose adjustments were required in over half the cases and were usually due to leukopenia. Infections occurring subsequent to thymoglobulin were not uncommon and reflected the immunosuppressive burden of the patient population.
回顾在接受他克莫司和霉酚酸酯的胰腺移植患者中使用抗胸腺细胞球蛋白的安全性和有效性。
对1995年至2000年间接受移植的45例患者进行回顾性单中心分析，这些患者接受了54个疗程的抗胸腺细胞球蛋白治疗，其中包括29例单独胰腺移植受者（16例单纯胰腺移植，13例肾移植后胰腺移植）的36个疗程，以及16例同时进行肾-胰腺移植患者的18个疗程。32例患者（71%）为初次胰腺移植，10例（22%）为二次移植，3例（7%）为三次移植。在54个治疗疗程中，19个（35%）用于诱导，27个（50%）用于原发性排斥反应，8个（15%）用于排斥反应的挽救治疗。所有排斥反应均经至少一个器官的活检证实。
抗胸腺细胞球蛋白的中位剂量为1.5mg/kg/d，平均6剂（范围3 - 10剂）。28个疗程（52%）需要减少剂量或中断治疗，最常见的原因是白细胞减少（n = 24）、发热（n = 2）和血小板减少（n = 2）。除3例患者外，其余患者均恢复使用抗胸腺细胞球蛋白，其中2例持续发热，1例感染。17例患者（38%）在30天内发生感染并发症（n = 25），包括细菌感染（n = 16）、巨细胞病毒感染（n = 4）、多瘤病毒感染（n = 1）、真菌感染（白色念珠菌，n = 1）、弓形虫病（n = 1）和埃立克体病（n = 2）。移植后淋巴细胞增生性疾病在抗胸腺细胞球蛋白治疗后平均70天发生在2例患者（4%）中。在接受抗胸腺细胞球蛋白诱导治疗的19例患者中，1例同时进行肾-胰腺移植、2例单纯胰腺移植和4例肾移植后胰腺移植受者发生排斥反应（发生率37%），而其余所有接受监测方案活检的患者均无排斥反应。在接受抗胸腺细胞球蛋白治疗排斥反应的35例患者中，26例患者（74%）排斥反应逆转。5例患者在30天内排斥反应复发，治疗后活检显示20例胰腺活检中有3例、8例肾活检中有2例存在持续性排斥反应。平均随访6个月后，实际患者和胰腺移植物存活率分别为93%和71%。
抗胸腺细胞球蛋白作为高危胰腺移植受者的诱导治疗有效，74%的患者排斥反应初步逆转。超过半数的病例需要调整剂量，通常是由于白细胞减少。抗胸腺细胞球蛋白治疗后发生感染并不罕见，反映了该患者群体的免疫抑制负担。
