Blood and Marrow Stem Cell Transplantation Program, Division of Hematology/Oncology, Department of Pediatrics, University of Michigan Medical Center,1500 E.Medical Center Drive, Ann Arbor, MI 48109, USA.
Biol Blood Marrow Transplant. 2012 Jul;18(7):1044-54. doi: 10.1016/j.bbmt.2011.11.031. Epub 2011 Dec 10.
Subacute lung disease, manifested as either obstructive (OLD) or restrictive (RLD) lung dysfunction, is a common complication following allogeneic stem cell transplantation. In each case, therapeutic options are limited, morbidity remains high, and long-term survival is poor. Between 2001 and 2008, 34 patients with noninfectious, obstructive (25) or RLD restrictive lung dysfunction (nine) received etanercept (Enbrel®, Amgen Inc.) 0.4 mg/kg/dose, subcutaneously, twice weekly, for 4 (group A) or 12 weeks (group B). Corticosteroids (if present at study entry) were kept constant for the initial 4 weeks of therapy and then tapered as tolerated. Thirty-one of 34 (91%) subjects were evaluable for response, and 10 (32%) met primary response criteria. There was no difference in response based on the duration of treatment (29% group A versus 35% group B; P = .99), the presence of RLD or OLD (33% versus 32%; P = .73), or the severity of pulmonary disease at study onset. Estimated 5-year overall survival rates following therapy were 61% (95% confidence interval, 46%-80%) for all subjects and 90% (95% confidence level, 73%-100%) for the 10 who met the primary response criteria. Five-year survival estimates for subjects treated with RLD was 44%, compared with 67% for those treated for OLD (P = .19). Etanercept was well tolerated, with no bacteremia or viremia observed. Pathogens were noted on posttherapy bronchoalveolar lavage in two cases. These data support the development of expanded clinical trials to study etanercept as a therapeutic agent for subacute lung injury after allogeneic stem cell transplantation.
亚急性肺疾病，表现为阻塞性（OLD）或限制性（RLD）肺功能障碍，是异基因干细胞移植后的常见并发症。在每种情况下，治疗选择都很有限，发病率仍然很高，长期存活率也很差。2001 年至 2008 年间，34 名非感染性、阻塞性（25 名）或 RLD 限制性肺功能障碍（9 名）患者接受依那西普（Enbrel®，安进公司）0.4mg/kg/剂量，皮下，每周两次，4 周（A 组）或 12 周（B 组）。如果在研究开始时存在皮质类固醇，则在治疗的最初 4 周内保持不变，然后根据耐受情况逐渐减少剂量。34 名患者中的 31 名（91%）可评估反应，10 名（32%）符合主要反应标准。根据治疗持续时间（A 组 29%与 B 组 35%；P=0.99）、RLD 或 OLD 的存在（33%与 32%；P=0.73）或研究开始时肺部疾病的严重程度，反应无差异。治疗后估计的 5 年总生存率为所有患者的 61%（95%置信区间，46%-80%）和符合主要反应标准的 10 名患者的 90%（95%置信水平，73%-100%）。RLD 治疗患者的 5 年生存率估计为 44%，而 OLD 治疗患者为 67%（P=0.19）。依那西普耐受性良好，未观察到菌血症或病毒血症。在 2 例患者的治疗后支气管肺泡灌洗中发现病原体。这些数据支持开展扩大临床试验，研究依那西普作为异基因干细胞移植后亚急性肺损伤的治疗药物。
