Humanized anti-CD25 monoclonal antibody treatment of steroid-refractory acute graft-versus-host disease: a Chinese single-center experience in a group of 64 patients

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic approach for hematologic malignancies. However, acute graft-versus-host disease (aGVHD), especially the refractory type, remains a serious barrier to successful allo-HSCT. Various second-line treatment regimens have been proposed; yet, to date, no standard treatment protocol has proven to be the best choice. The anti-CD25 monoclonal antibody (mAb) is one of the most used second-line treatment choices for steroid-refractory aGVHD. Unfortunately, China has limited experience with regard to the application of anti-CD25 mAb in the treatment of steroid-refractory aGVHD. Herein, we report our experience with humanized anti-CD25 mAb treatment in a group of Chinese allo-HSCT patients affected by steroidrefractory aGVHD. Between December 2011 and April 2014, 352 patients were diagnosed with aGVHD at the Department of Hematology in the First Affiliated Hospital of Soochow University, and 64 patients did not respond to first-line treatment and they were enrolled into this study consecutively. The median time of steroid-refractory aGVHD onset after HSCT was 1.67 months (range, 0.73– 14.2 months) in this group of patients. The institutional review board of the First Affiliated Hospital of Soochow University approved this study protocol and the signed informed consent was provided by the enrolled patients or their guardians if the patients were younger than 18 years old. The patient characteristics are summarized in Table 1, and the severity of aGVHD was graded according to the Keystone 1994 consensus criteria. On using standard-dose methylprednisolone (2 mg/kg/day) treatment, if aGVHD still progressed within 3 days or if it was not alleviated after treatment for 5–7 days, then the aGVHD is considered steroid refractory and second-line therapy can be given, and simultaneously, the steroid should be tapered. Humanized anti-CD25 mAb (Xenopax, CP Guojian Pharm, Shanghai, China) that has the same amino-acid sequence as daclizumab (Zenapax, Roche, Nutley, NJ, USA) was administered at a dosage of 1 mg/kg intravenously on days 1, 4, 8, 15 and 22. If the skin or gastrointestinal tract aGVHD did not respond to the systemic glucocorticoid treatment, topically worked glucocorticoid in ointment or capsule was given to avoid the exacerbation of aGVHD due to the tapering of systemic steroid, respectively. In our study, the responses of patients were concluded at day 28 after therapy initiation. Complete response (CR) was defined as resolution of all signs and symptoms of aGVHD in all organs without intervening salvage therapy; and partial response (PR) was an improvement of at least one stage in one or more organs without progression in any other organ. No response (NR) was defined as the absence of improvement or aGVHD progression within 28 days after therapy initiation. Previous studies have demonstrated that daclizumab treatment for steroid-resistant aGVHD could produce a response rate ranging between 29 and 68%. However, our results were even more encouraging, a total response rate of 83% (53/64) was achieved, which included a CR rate of 58% (37/64) and a PR rate of 25% (16/64). Although a total response rate of 89% (31/35) achieved in steroid-refractory aGVHD patient subgroup with single organ involved is higher than that of 76% (22/29) achieved in multiorgan-involved patient subgroup, there is no significant difference between these two groups (P= 0.15). Analyzed from the