抗CD25单抗联合ATG在非血缘造血干细胞移植激素耐药重度aGVHD治疗的应用

Anti-CD25 monoclonal antibody with antithymocytic globulin for steroid-resistant severe acute graft-versus-host disease after unrelated donor hematopoietic stem cell transplantation

目的探讨抗CD25单抗（antiCD25）联合兔抗人胸腺细胞球蛋白（ATG）在非血缘造血干细胞移植（UD-HSCT）耐激素重度急性移植物抗宿主病（aGVHD）治疗的效果。方法回顾性分析10例（12例次）白血病患者在UD—HSCT过程出现耐激素重度aGVHD后，接受标准剂量antiCD25与中低剂量ATG联合治疗后的效果以及生存率、感染、复发等情况。结果10例患者中有8例完全缓解，2例获得部分缓解；完全缓解的8例中，有2例分别在移植后3～3．5月再出现aGVHD达Ⅲ度，经再应用antiCD25联合ATG治疗均获完全缓解；12例次联合用药，中位起效时间5d（3～10d）。在完全缓解的10例次中，中位达到完全缓解时间12d（8--30d）。生存时间超过3月以上的8例患者中，7例患者出现慢性移植物抗宿主病（cGVHD），其中广泛性cGVHD4例；未见白血病复发情况。联合治疗后5例患者出现真菌感染，反复CMV-Ag检测阳性者2例。移植后随访2年余，仍存活5例，生存时间均超过2年；有5例死亡，其中1例生存时间超过1年，4例生存时间小于6月。死亡原因包括：aGVHD2例，cGVHD引致多器官功能衰竭1例，真菌感染2例。结论antiCD25联合中低剂量ATG治疗UD—HSCT后耐激素重度aGVHD，可能有较好的治疗缓解率及长期生存率。

Objectives To study the effect of anti-CD25 monoclonal antibody （mAb） combined with antithymocytic globulin （ATG） in the treatment of severe steroid-resistant acute graft-versus-host disease （aGVHD） after unrelated donor hematopoietic stem cell transplantation （UD-HSCT）. Methods Ten leukemic patients who developed severe steroid-resistant aGVHD during UD-HSCT received a standard dose of anti-CD25 mAb and a medium or low dose of ATG. The effect on aGVHD control, patients＇ survival, infection and relapse after the therapy were analyzed. Results Eight of the 10 patients had complete remission and 2 had partial remission after the combined therapy. In the 8 patients with complete remission, 2 developed third degree aGVHD 3-3.5 months after the transplantation, and were managed with a second combined therapy to successfully achieve complete remission. In the total of 12 combined treatments, the median time of therapeutic effect was 5 days （3-10 days）; the median complete relief time was 12 days （8-30 days） in the 10 cases. Among the 8 patients who survived for more than 3 months, 7 were diagnosed to have chronic GVHD including 4 with extensive chronic GVHD. No relapse of leukemia was found in these patients. Five patients survived the 2-year-long follow-up after the transplantation with survival time over 2 years; of the 5 patients who died within 2 years after the transplantation, 1 survived for more than one year, and 4 for less than 6 months. Two patients died from invasive fungal infection, two from aGVHD and one from cGVHD-induced multiple organ failure. Conclusions Anti-CD25 mAb combined with ATG has good therapeutic effect on steroid-resistant sever aGVHD and may help achieve high complete remission rate and long-term survival in leukemic patients after UD-HSCT.