Branco Carlos, Prieto David, Antunes André, Batista Manuel, J Antunes Manuel
CCT-CHUC, Portugal.
Rev Port Cir Cardiotorac Vasc. 2017 Jul-Dec;24(3-4):119.
The management of induction and maintenance immunosuppression therapy after heart transplantation (HT) remains a controversial issue. The dosage and the timing has been a changing target. We aimed at evaluate the incidence of acute cellular rejection (ACR) [≥1R grade], major infection and survival in first year after HT in patients receiving two different induction immunosuppression regimes and with a reduction in intensity of triple maintenance immunosuppression dose.
From November-2003 to June-2016, 317 patients were submitted to HT. After excluding those with pediatric age (n=8), those with previous renal or hepatic transplantation (n=2), those submitted to retransplantation (n=2), patients with early death without endomiocardial biopsy (n=10) and those in a transition maintenance regime (n=26), the study population resulted in 269 patients. These patients were divided in two groups: patients receiving the previous regime of two doses of basiliximab (group A, n=211) and those receiving a single dose of basiliximab (group B, n=58). All the patients were treated with a maintenance standard triple immunosuppressive regimen of corticosteroids, an inhibitor of calcineurin and mycophenolate mofetil but more immunosuppressive load in group A.
Mean age of the recipients (group A vs. group B) was 54.6±10.6vs.55.0±9.8 years (p=0.808); 77.3%vs.75.9% were male (p=0.861); 28.4%vs.28.1% were diabetic (p=0.957); and ischemic etiology was present in 39.8%vs 41.0% of the patients (p=0.798), respectively. No differences were found, at first year, between the two groups concerning global ACR incidence (55.0%vs.56.9%, p=0.882, respectively) but major ACR (≥2R grade) was slightly superior in group B (16.6%vs.27.6%, p=0.080, respectively). Time-free from major ACR at 3rd, 6th and 12th months was, respectively 91.0±2.0%vs.84.5%±4.8%; 86.7±2.3%vs.74.1±5.7%; and 83.4±2.6%vs.72.4±5.9% (p=0.048). Time-free from major infection at 3rd, 6th and 12th months was, respectively 89.6±2.1%vs.82.8±5.0%; 87.7±2.3%vs.79.3±5.3%; and 84.4±2.5%vs.79.3±5.3% (p=0.253). No differences were found concerning survival at 3rd, 6th and 12th months (94.3±1.6%vs.94.8±2.9%; 92.4±1.8%vs.93.1±3.3%; and 90.0±2.1%vs.91.4±3.7%, (p=0.771) respectively).
With this study, we verified that lowering doses of induction and maintenance therapy was responsible for increase cases of major ACR at first year of heart transplant. However, no differences were found concerning the incidence of major infection and early survival. Hence, effective immunosuppression induction regimen can apparently be done safely with a single dose regime without compromising survival at first year after HT.
心脏移植（HT）后诱导和维持免疫抑制治疗的管理仍然是一个有争议的问题。剂量和时机一直是变化的目标。我们旨在评估接受两种不同诱导免疫抑制方案且三联维持免疫抑制剂量强度降低的患者在HT后第一年的急性细胞排斥反应（ACR）[≥1R级]、主要感染发生率和生存率。
2003年11月至2016年6月，317例患者接受了HT。排除儿童患者（n = 8）、既往有肾或肝移植史的患者（n = 2）、再次移植的患者（n = 2）、未进行心内膜心肌活检而早期死亡的患者（n = 10）以及处于过渡维持方案的患者（n = 26）后，研究人群为269例患者。这些患者分为两组：接受两剂巴利昔单抗既往方案的患者（A组，n = 211）和接受一剂巴利昔单抗的患者（B组，n = 58）。所有患者均接受皮质类固醇、钙调神经磷酸酶抑制剂和霉酚酸酯的标准三联维持免疫抑制方案治疗，但A组的免疫抑制负荷更高。
接受者的平均年龄（A组与B组）分别为54.6±10.6岁和55.0±9.8岁（p = 0.808）；男性分别为77.3%和75.9%（p = 0.861）；糖尿病患者分别为28.4%和28.1%（p = 0.957）；缺血性病因分别存在于39.8%和41.0%的患者中（p = 0.798）。在第一年，两组之间的总体ACR发生率没有差异（分别为55.0%和56.9%，p = 0.882），但主要ACR（≥2R级）在B组略高（分别为16.6%和27.6%，p = 0.080）。第3、6和12个月无主要ACR的时间分别为91.0±2.0%对84.5%±4.8%；86.7±2.3%对74.1±5.7%；83.4±2.6%对72.4±5.9%（p = 0.048）。第3、6和12个月无主要感染的时间分别为89.6±2.1%对82.8±5.0%；87.7±2.3%对79.3±5.3%；84.4±2.5%对79.3±5.3%（p = 0.253）。在第3、6和12个月的生存率没有差异（分别为94.3±1.6%对94.8±2.9%；92.4±1.8%对93.1±3.3%；90.0±2.1%对91.4±3.7%，p = 0.771）。
通过本研究，我们证实降低诱导和维持治疗剂量会导致心脏移植第一年主要ACR病例增加。然而，在主要感染发生率和早期生存率方面没有发现差异。因此，有效的免疫抑制诱导方案显然可以通过单剂量方案安全地进行，而不会影响HT后第一年的生存率。
