Trivedi H L, Kaneku H, Terasaki P I, Feroz A, Vanikar A V, Trivedi V B, Khemchandani S I, Dave S D, Modi P R, Jahr F, Idica A, Everly M J
Institute of Kidney Diseases and Research Centre-Institute of Transplantation Sciences (IKDRC-ITS), Ahmedabad, India.
Clin Transpl. 2009:265-80.
A total of 69 individuals received a kidney from a living donor after a TLI-based clonal deletion protocol with no post-transplant maintenance immunosuppression planned. If needed, immunosuppression was started on a patient-specific basis, adding one drug at a time, a strategy we AWN". call "Drugs Added When Needed," or "DAWN. Following this strategy, at last follow-up 40 of the 69 patients (58%) had to be rescued by conventional immunosuppression, 23 (33%) had to be started on daily prednisone and six (9%) remained with no maintenance immunosuppression. The overall rate of de novo donor-specific antibody produced was 36% (in 25 of the 69 patients), and mean time to detection was about four months. The incidence of acute rejection episodes that displayed humoral components was 27% (19 cases), of which 14 were pure antibody-mediated rejection, five combined antibody- and T-cell-mediated rejection, and six were episodes (9%) of pure T-cell-mediated rejection. Finally, this study shows that although complete clonal deletion was not achieved, an important proportion of patients--42%, or 29 of the original 69--could be maintained with prednisone alone or even with no immunosuppression for a total mean follow-up of 13.3 months. Moreover, 16 patients with recent follow-up are surviving with no maintenance immunosuppression or just on prednisone. The mean serum creatinine at last follow-up for these 16 patients is 1.33 +/- 0.2 mg/dL with a mean follow-up of 19.3 months. Clonal deletion can be used to transplant patients without maintenance immunosuppression, adding drugs only as needed.
共有69名个体在基于胸腺淋巴细胞清除(TLI)的克隆清除方案后接受了活体供肾,且未计划进行移植后维持免疫抑制。如有需要,根据患者具体情况开始免疫抑制,每次添加一种药物,我们将这种策略称为“按需加药”(DAWN)。按照该策略,在最后一次随访时,69名患者中有40名(58%)不得不接受传统免疫抑制治疗来挽救,23名(33%)不得不开始每日服用泼尼松,6名(9%)仍未进行维持免疫抑制治疗。新产生的供者特异性抗体总体发生率为36%(69名患者中有25名),平均检测时间约为4个月。表现出体液成分的急性排斥反应发生率为27%(19例),其中14例为纯抗体介导的排斥反应,5例为抗体和T细胞介导的混合排斥反应,6例为纯T细胞介导的排斥反应(9%)。最后,这项研究表明,尽管未实现完全克隆清除,但相当一部分患者——42%,即最初69名患者中的29名——在平均13.3个月的总随访期内仅用泼尼松或甚至不进行免疫抑制就能维持。此外,16名近期接受随访的患者在未进行维持免疫抑制治疗或仅服用泼尼松的情况下存活。这16名患者在最后一次随访时的平均血清肌酐为1.33±0.2mg/dL,平均随访时间为19.3个月。克隆清除可用于对患者进行无维持免疫抑制的移植,仅按需添加药物。