[Clinical study of anti-human T cell porcine immunoglobulin with recombinant human tumor necrosis factor-α receptor II: IgG Fc in the treatment of 35 cases of grade III/IV acute graft-versus-host disease after allo-HSCT].

Objective: To evaluate the efficacy and safety of anti-human T lymphocyte porcine immunoglobulin (P-ATG) with recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (rhTNFR∶Fc, Etanercept) on grade Ⅲ/Ⅳ acute graft-versus-host disease (aGVHD) after allogenic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Thirty-five patients with Grade Ⅲ/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 grade Ⅲ/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 grade Ⅲ 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 grade Ⅲ aGVHD group was also higher than of grade Ⅳ 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 grade Ⅲ aGVHD group was superior to grade Ⅳ 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.

Urinary magnesium loss in aging diabetic mellitus rats.

Past studies on urinary loss of magnesium (Mg) have focused on young diabetic rats. The aims of the present study were to determine the rapidity at which glycosuria and magnesuria occur after the induction of diabetes mellitus (DM) in old male rats, and the maximal amount of Mg and glucose (Glu) loss in the urine and whether or not the loss is persistent and (3) the most sensitive means of correlating the Mg and Glu loss in the urine. Three methods of expressing urinary Mg and Glu concentrations were selected: Method A: mg/24 h; Method B: mg/24 h/kg body weight (BW), and Method C: ratio of Mg to creatinine (Mg/Crea) or ratio of Glu to Crea (Glu/Crea). Our study indicated a maximal and rapid loss of Mg and Glu occurring within 1 week after induction of DM (by streptozotocin injection) and remained in effect for 6 weeks, the end of the study. The urinary Mg loss due to DM correlated best with urinary Glu when expressed as mg/24 h/kg BW. In addition, the increase in urinary Mg concentration paralleled the degree of glycosuria and reached a maximum of 5-12 times baseline values when expressed by Method B. This was 4-10 times when expressed by Method A, and 2-6 times when expressed by Method C. Since polyuria is a feature of DM, we also correlated the relationship between these two factors, and found a significantly positive correlation (r = 0.735) particularly when Mg was expressed as mg/24 h. In summary, rapid and significant urinary Mg loss is observed in old rats made diabetic with streptozotocin.(ABSTRACT TRUNCATED AT 250 WORDS)