Salter S P, Salter M M, Kirklin J K, Bourge R C, Naftel D C
University of Alabama at Birmingham, Department of Radiation Oncology 35233, USA.
Int J Radiat Oncol Biol Phys. 1995 Aug 30;33(1):83-8. doi: 10.1016/0360-3016(95)00135-L.
Recurrent acute cardiac allograft rejection is an important cause of repeat hospitalization and a major mode of mortality, particularly during the 6 months immediately following transplant. Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecdotal reports of clinical experience have also suggested efficacy of TLI in treatment of recurrent cardiac rejection. The purpose of this study is to evaluate the safety and efficacy of TLI for treatment of early or recurrent heart transplant rejection.
Between January 1990 and June 1992, 49 patients postallograft cardiac transplant were given courses of TLI for treatment of early or recurrent rejection after conventional therapy with Methylprednisolone, antithymocyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a second TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6). The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment was 8 to 106 days. These variations were secondary to leukopenia or thrombocytopenia.
The mean posttransplant follow-up is 15 +/- 1.2 months (maximum 27 months). Among patients initiating TLI within 1 month posttransplant (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/month post-TLI (p < 0.001). For those who began TLI 1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/patient/month (p < 0.001). When TLI was started more than 3 months posttransplant (n = 11), the pre-TLI and post-TLI rejection frequencies were 0.67 and 0.07/patient/month (p < 0.001), respectively. The reduced post-TLI rejection frequencies were maintained to 24 months. There was no increase in the frequency of infection after TLI, nor were there any deaths during or immediately following TLI.
Total lymphoid irradiation is a safe and effective adjunct for prolonged control of early or recurrent cardiac rejection. Bone marrow suppression is transient in nearly all patients and is not associated with an increased incidence of infection. The long-term benefits, possible late deleterious effects, and the potential role of TLI as induction therapy remain to be elucidated.
心脏移植术后急性排斥反应复发是再次住院的重要原因及主要死亡方式，尤其在移植后的头6个月内。实验表明，在移植前给予全身淋巴照射（TLI）可诱导部分耐受状态。临床经验的轶事报道也提示TLI治疗心脏排斥反应复发有效。本研究旨在评估TLI治疗早期或复发性心脏移植排斥反应的安全性和有效性。
1990年1月至1992年6月期间，49例心脏移植术后患者在接受甲泼尼龙、抗胸腺细胞球蛋白、OKT3和甲氨蝶呤常规治疗后，接受TLI疗程以治疗早期或复发性排斥反应。2例患者未完成治疗，未纳入评估。另外2例患者接受了第二个TLI疗程，共进行了49个疗程。TLI的适应证为早期排斥反应（n = 5）、复发性排斥反应（n = 38）和伴有血管炎的复发性排斥反应（n = 6）。TLI方案的剂量目标是每周两次，分10次给予8 Gy。使用三个独立野覆盖所有主要含淋巴结区域。实际平均剂量为7 Gy（范围2.4 - 8.4 Gy），治疗持续时间为8至106天。这些差异继发于白细胞减少或血小板减少。
移植后平均随访时间为15±1.2个月（最长27个月）。在移植后1个月内开始TLI的患者中（n = 15），排斥反应频率从TLI前的1.83次/患者/月降至TLI后的0.13次/患者/月（p < 0.001）。对于在移植后1 - 3个月开始TLI的患者（n = 21），排斥反应从1.43次/患者/月降至0.10次/患者/月（p < 0.001）。当在移植后3个月以上开始TLI时（n = 11），TLI前和TLI后的排斥反应频率分别为0.67次/患者/月和0.07次/患者/月（p < 0.001）。TLI后排斥反应频率降低的情况维持至24个月。TLI后感染频率未增加，TLI期间或之后也无死亡病例。
全身淋巴照射是长期控制早期或复发性心脏排斥反应的安全有效辅助治疗方法。几乎所有患者的骨髓抑制都是短暂的，且与感染发生率增加无关。TLI作为诱导治疗的长期益处、可能的晚期有害影响及潜在作用仍有待阐明。
