Perales M-A, Ishill N, Lomazow W A, Weinstock D M, Papadopoulos E B, Dastigir H, Chiu M, Boulad F, Castro-Malaspina H R, Heller G, Jakubowski A A, O'Reilly R J, Small T N, Young J W, Kernan N A
Allogeneic Bone Marrow Transplantation Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Bone Marrow Transplant. 2007 Sep;40(5):481-6. doi: 10.1038/sj.bmt.1705762. Epub 2007 Jul 9.
Daclizumab has been shown to have activity in acute GVHD, but appears to be associated with an increased risk of infection. To investigate further the long-term effects of daclizumab, we performed a retrospective review of 57 patients who underwent an allogeneic hematopoietic stem cell transplant from January 1993 through June 2000 and were treated with daclizumab for steroid-refractory acute GVHD. The median number of daclizumab doses given was 5 (range 1-22). GVHD was assessed at baseline, days 15, 29 and 43. By day 43, 54% patients had an improvement in their overall GVHD score, including 76% patients aged < or =18. Opportunistic infections developed in 95% patients. Forty-three patients (75%) died following treatment with daclizumab. The causes of death included active GVHD and infection (79%), active GVHD (5%), chronic GVHD (2%) and relapse (14%). Patients with grade 3-4 GVHD had a significantly shorter median survival than patients with grade 1-2 GVHD (2.0 vs 5.1 months, P=0.001). Daclizumab has no infusion-related toxicity, is active in steroid-refractory GVHD, especially among pediatric patients, but is associated with significant morbidity and mortality due to infectious complications. Careful patient selection and aggressive prophylaxis against viral and fungal infections are recommended.
已证明达克珠单抗在急性移植物抗宿主病（GVHD）中有活性，但似乎与感染风险增加有关。为了进一步研究达克珠单抗的长期影响，我们对1993年1月至2000年6月期间接受异基因造血干细胞移植并因类固醇难治性急性GVHD接受达克珠单抗治疗的57例患者进行了回顾性研究。达克珠单抗给药的中位数剂量为5剂（范围1 - 22剂）。在基线、第15天、第29天和第43天评估GVHD。到第43天，54%的患者总体GVHD评分有所改善，其中年龄≤18岁的患者中有76%。95%的患者发生了机会性感染。43例患者（75%）在接受达克珠单抗治疗后死亡。死亡原因包括活动性GVHD和感染（79%）、活动性GVHD（5%）、慢性GVHD（2%）和复发（14%）。3 - 4级GVHD患者的中位生存期明显短于1 - 2级GVHD患者（2.0个月对5.1个月，P = 0.001）。达克珠单抗无输注相关毒性，在类固醇难治性GVHD中具有活性，尤其是在儿科患者中，但由于感染并发症会导致显著的发病率和死亡率。建议仔细选择患者并积极预防病毒和真菌感染。
