1.
Effectiveness of in vivo T-cell-depleted regimen containing porcine anti-lymphocyte globulin or rabbit anti-thymocyte globulin in preventing acute graft-versus-host disease after haploidentical haematopoietic stem cell transplantation
Xu, Z., Zhou, X., Zhao, X., Lu, X., Wang, H.
British journal of haematology. 2023
Abstract
To compare the clinical efficacy of porcine anti-lymphocyte globulin (p-ALG) and rabbit anti-thymocyte globulin (r-ATG) in the treatment of haematological malignancies using haploidentical haematopoietic stem cell transplantation (haplo-HSCT), this study was conducted. The incidences of neutrophil and platelet engraftment, respectively, were 100%, 93.6% and 94.4%; 100%, 93.6% and 90.3% in p-ALG 75 mg/kg (n = 57), p-ALG 90 mg/kg (n = 49), and r-ATG 7.5 mg/kg (n = 72). The median time to neutrophil engraftment and platelet engraftment were 11, 12 and 12 days (p = 0.032); 13, 14 and 13 days (p = 0.013), respectively. The incidence of grades II-IV acute graft-versus-host disease and cumulative incidence of chronic graft-versus-host disease were 16.7% versus 12.5% versus 13.3% (p = 0.817) and 14.7% versus 12.1% versus 19.5% in p-ALG 75 mg/kg, p-ALG 90 mg/kg and r-ATG groups. Notably, the cytomegalovirus infection rate in the p-ALG 75 mg/kg group was significantly lower than the other two groups. The cumulative incidence of 2-year relapse and 2-year overall survival rates were similar (p = 0.901, p = 0.497). The lower dose of p-ALG (75 mg/kg) had a similar efficacy and safety profile compared with r-ATG (7.5 mg/kg) in the setting of haplo-HSCT. Therefore, p-ALG (75 mg/kg) may be an appropriate alternative to r-ATG in the conditioning regimen of haplo-HSCT.
2.
Delay expression of NKp30 on NK cells correlates with long-term mycophenolate mofetil treatment and higher EBV viremia post allogenic hematological stem cells transplantation
Yu, X., Cao, X., Yan, H., Luo, X. Y., Zhao, X., Sun, Y., Wang, Y., Xu, L., Zhang, X., Chang, Y., et al
Clinical immunology (Orlando, Fla.). 2019
Abstract
Mycophenolate mofetil (MMF) is an immunosuppressive agent that is widely used in graft-versus-host disease prophylaxis because of its inhibitory function on T cells and B cells. However, the effect of MMF on natural killer cell reconstitution after allogenic hematological transplantation is largely unknown. The present study examined the effects of different MMF administration durations after haploidentical allo-HSCT on NK cell reconstitution. Ninety patients were enrolled in this study and defined into two groups in term of MMF duration. We found that MMF patients in the long-term MMF group were associated with a poor reconstitution of NK cells and a significantly lower cytotoxicity from day 30 to day 180 post-transplantation. Especially, the long-term MMF group inhibits reconstitution of NKp30 NK subsets, which correlated with higher risk of EBV viremia. Multivariate analysis showed that a better reconstitution of NKp30 cells was associated with lower EBV viremia (HR0.957, p=.04). In vitro experiments demonstrated that the active metabolite of MMF, mycophenolic acid (MPA), inhibited the proliferation and cytotoxicity of NK cells from healthy donors or patients at day 30 post-transplantation. In summary, our findings demonstrated that long-term MMF administration delayed the quality and quantity of NK cells, especially NKp30 subpopulations, which was associated with decreased EBV viremia post allogeneic HSCT.
3.
The efficacy and safety of sirolimus-based graft-versus-host disease prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials
Wang, L., Gu, Z., Zhai, R., Li, D., Zhao, S., Luo, L., Zhao, X., Wei, H., Pang, Z., Wang, L., et al
Transfusion. 2015;55(9):2134-41
Abstract
BACKGROUND The efficacy and safety of sirolimus (SIR)-based graft-versus-host disease (GVHD) prophylaxis in patients who were subjected to allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain to be clarified; this meta-analysis was conducted to evaluate these factors. STUDY DESIGN AND METHODS Data from original research were obtained from PubMed, Embase, and Cochrane central register of controlled trials databases. Randomized controlled trials (RCTs) evaluating the efficacy of SIR-based prophylaxis in allo-HSCT were included. The risk ratio (RR), with a 95% confidence interval (CI), was used to pool data. The random effects model was used, irrespective of the presence or absence of heterogeneity. RESULTS Five RCTs were included in the meta-analysis. SIR was observed to significantly decrease the incidence of Grade II to IV acute GVHD (aGVHD; RR, 0.65; 95% CI, 0.47-0.89). However, the incidence of Grade III to IV aGVHD and chronic GVHD was not decreased (RR, 0.91; 95% CI, 0.59-1.40; RR, 1.04; 95% CI, 0.88-1.23, respectively). An analysis of the toxic effects of SIR revealed that SIR effected a significant increase in the incidence of sinusoidal obstructive syndrome (RR, 2.24; 95% CI, 1.26-4.01), while that of thrombotic microangiopathy was not significantly increased (RR, 2.48; 95% CI, 0.87-7.06). Moreover, SIR did not improve event-free survival and overall survival (RR, 0.97; 95% CI, 0.85-1.10; and RR, 0.92; 95% CI, 0.82-1.02, respectively). CONCLUSION This meta-analysis indicated that the SIR-based regimen is an effective and safe alternative prophylaxis strategy for GVHD.