抗人T细胞猪免疫球蛋白联合重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗异基因造血干细胞移植后Ⅲ/Ⅳ度急性移植物抗宿主病35例临床研究

OBJECTIVE: To evaluate the efficacy and safety of anti-human T lymphocyte porcine immunoglobulin（P-ATG）with recombinant human tumor necrosis factor-α receptorⅡ:IgG Fc fusion protein（rhTNFR∶Fc，Etanercept）on gradeⅢ/Ⅳ acute graft-versus-host disease（aGVHD）after allogenic hematopoietic stem cell transplantation（allo-HSCT）. METHODS: Thirty-five patients with GradeⅢ/Ⅳ aGVHD who received P-ATG with etanercept therapy after allo-HSCT were retrospectively analyzed. P-ATGs（5 mg· kg(−1)· d(−1)） were administrated for 3 to 5 days, and then 5mg/kg was sequentially administrated, QOD to BIW. Etanercepts were administrated 25 mg, twice a week（12.5 mg, BIW for pediatric patients）. RESULTS: Among the 35 patients with gradeⅢ/Ⅳ aGVHD, 21 were males and 14 females, with a median age of 10（3–54）years. A total of 19 cases of acute myeloid leukemia, 13 of acute lymphoblastic leukemia, 1 of severe aplastic anemia, 1 of myelodysplastic syndrome, and 1 of mixed phenotypic acute leukemia were noted. The overall response（OR）rate of P-ATG with etanercept was 85.7％（30/35）, with complete response（CR）and partial response（PR）rates of 34.3％（12/35）and 51.4％（18/35）, respectively, on day 28. The OR rate of gradeⅢ aGVHD group was higher than of grade IV aGVHD group［100％（19/19）vs. 68.8％（11/16）, P＝0.004］. On day 56, the OR rate became 77.2％（27/35）, with CR and PR rates of 62.9％（22/35）and 14.3％（5/35）, respectively．The OR rate of gradeⅢ aGVHD group was also higher than of gradeⅣ aGVHD group［89.5％（17/19）vs. 62.5％（10/16）, P＝0.009］. Thirty-five patients had no adverse effects such as fever, chills, and rash during the P-ATG infusion, and no obvious liver and kidney function damage was observed after treatment. The main treatment-related complication was infection. The reactivation rates of CMV and EBV were 77.1％（27/35）and 22.9％（8/35）, respectively, and the bacterial infection rate was 48.6％（17/35）. With a median follow-up time of 13（1–55）months after HSCT, the 1-year and 2-year OS rates were（68.1±8.0）％ and（64.3±8.4）％, respectively. The 1-year OS rate of gradeⅢ aGVHD group was superior to gradeⅣ aGVHD group［（84.2±8.4）％ vs.（47.6±13.1）％, χ(2)＝3.38, P＝0.05］. CONCLUSION: This study demonstrated that P-ATG with etanercept was effective and safe in treating grade Ⅲ–Ⅳ aGVHD after allo-HSCT.