The impact of positive T-cell lymphocytotoxic crossmatch on intestinal allograft rejection and survival
The impact of positive T-cell lymphocytotoxic crossmatch on intestinal allograft rejection and survival
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DOI：
10.1016/s0041-1345(00)01181-7
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发表时间：
2000-09-01
影响因子：
0.9
通讯作者：
Abu-Elmagd, K
中科院分区：
文献类型：
--
作者：
Bond, G;Reyes, J;Abu-Elmagd, K
材料与方法在9年的时间里，124例患者在本中心接受了130例同种异体肠移植：51个离体肠和79个复合内脏移植(62个肝/肠和17个多个内脏)。其中，51%是男性，58%是儿童。所有捐献者都是身体，ABO完全相同。人类白细胞抗原配型是随机的，没有试图对移植物进行免疫调节。基线免疫抑制药物为他克莫司和类固醇。最后17例患者使用Daclizumab作为诱导治疗，OKT3用于治疗类固醇耐药性排斥反应。27例同种异体移植物中，4例XM阳性。2 3阴性XM)，移植后2 4h内单次静脉输注未修饰的供者骨髓细胞(3~5×10 8个/kg体重)。XM试验是在所有患者中进行的，方法是在移植前立即获取受者血清，检测针对供者T淋巴细胞的细胞毒抗体活性，如前所述。2为缩短冷缺血时间，常在XM检查结果出来前开始受体手术。移植物中有23例(18%)二硫苏糖醇(DTT)阳性。所有移植物均为一期移植物，其中7例(30%)为离体肠，16例(70%)为含肝的复合内脏移植物。12例为儿童，11例为成人，成年女性相对占优势(39%)。XM阳性和阴性受者的临床特征相似，包括腹部手术次数、手术时间、冷缺血时间、供受者巨细胞病毒状态和中位随访期。供者和受者的手术以及围手术期的管理策略在两组中都是相同的，如其他地方所述。4、5采用Kaplan-Meier法计算生存率。结果平均随访27个月，23例XM阳性移植物中有10例(离体肠2例，复合内脏8例)失活，总存活率为57%。造成10例移植物(患者)丢失的原因是机会性感染5例(PTLD=3例，巨细胞病毒1例，真菌败血症1例)，排斥反应3例(急性=2例，慢性=1例)，1例升主动脉夹层。剩余的移植物(肝/肠)通过高淋巴细胞毒抗体效价(1：512)移植给1例黑人儿童受者，移植后4天死于移植物失败。尽管免疫组织化学和病理研究未能证实诊断，但不能排除这种情况下的超急性排斥反应。以阴性的XM移植物为对照，预先形成的淋巴细胞毒性抗体的存在对5年精算(Kaplan-Meier)患者和移植物存活率没有显著影响。
MATERIALS AND METHODSOver a 9-year period, 124 consecutive patients received a total of 130 intestinal allografts at our center: 51 isolated intestines and 79 composite visceral grafts (62 liver/intestine and 17 multivisceral). Of these, 51% were male and 58% were children. All donors were cadaveric and ABO identical. The HLA match was random and no attempts were made to immunomodulate the graft. The baseline immunosuppression was tacrolimus and steroids. Daclizumab was used as an induction therapy for the last 17 patients and OKT3 was utilized to treat steroid-resistant rejection. In 27 allografts (4 positive XM. 23 negative XM), a single dose (3 to 5× 10 8 cells/kg body weight) of unmodified donor bone marrow cells were infused intravenously within 24 hours after graft implantation. The XM test was performed in all patients by obtaining recipient sera immediately before transplantation that tested for cytotoxic antibody activity against donor T lymphocytes as previously described. 2 To shorten the cold-ischemia time, the recipient operation was often started before the results of the XM were available. The XM was positive with dithiothreitol (DTT) in 23 (18%) grafts. All were primary grafts with 7 (30%) isolated intestines and 16 (70%) composite visceral grafts that contained liver. Twelve were children and 11 were adults with a relative predominance of adult females (39%). The clinical features of both positive and negative XM recipients were similar, including number of previous abdominal operations, operative time, cold-ischemia time, donor/recipient CMV status, and median follow-up period. The donor and recipient operations as well as the perioperative management strategy were the same in both groups as described elsewhere. 4, 5 The Kaplan-Meier method was used to calculate survival rates. Chi-square and standard t tests were used for statistical analysis.RESULTSWith a mean follow-up of 27 months, 10 (2 isolated intestine, 8 composite visceral) of the 23 positive XM allografts were lost, with an overall survival of 57%. The causes of the 10 graft (patient) losses were opportunistic infections in 5 (PTLD= 3, CMV= 1, fungal sepsis= 1), rejection in 3 (acute= 2, chronic= 1), and dissection of the ascending thoracic aorta in 1. The remaining graft (liver/intestine) was transplanted across a high-lymphocytotoxic antibody titer (1: 512) to a black pediatric recipient who died of primary graft failure 4 days after transplantation. Hyperacute rejection could not be excluded in such a case despite failure of the conducted immunohistochemical and pathologic studies to confirm the diagnosis. Using the negative XM grafts as control, the presence of preformed lymphocytotoxic antibodies did not significantly affect the 5-year actuarial (Kaplan–Meier) patient and graft survival.