1.
Evaluating the Impact of Post-Transplant Cyclophosphamide and Anti-Thymocyte Globulin on CMV Reactivation Following Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Literature Review
Dybko, J., Giordano, U., Pilch, J., Mizera, J., Borkowski, A., Dereń-Wagemann, I.
Journal of clinical medicine. 2023;12(24)
Abstract
Anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) are two frequently utilised strategies in graft-versus-host disease (GvHD) prophylaxis following allogeneic hematopoietic cell transplantation (allo-HCT), currently approved for different recipient-donor settings. In addition, being efficacious in preventing GvHD owing to their T-cell depleting capacity, the employment of these two agents increases the risk of infections, including CMV reactivation, which stands as one of the most common and serious infections following allo-HCT. We performed a systematic literature review of articles published until 1 September 2023, through PubMed, MEDLINE, and Scopus, with the main endpoint being CMV reactivation after PTCy or ATG allo-HCT. The majority of the studies included in the analysis provide supporting evidence for a reduced risk of CMV reactivations following the use of PTCy compared to ATG, although not all findings reached statistical significance. Additionally, it appears that utilising a haploidentical donor leads to a higher incidence of CMV infections and clinically significant CMV infections (CS-CMVis) compared to other donor settings in PTCy allo-HCT. This study aims to compare the risk of CMV infections following allo-HCT in patients who have received either ATG or PTCy as GvHD prophylaxis and discuss other factors that could influence the infectious outcomes of patients who have undergone allo-HCT.
2.
Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis
Ahn, H., Tay, J., Shea, B., Hutton, B., Shorr, R., Knoll, G. A., Cameron, D. W., Cowan, J.
Transfusion. 2018
Abstract
BACKGROUND Prophylactic immunoglobulin has been used with varying efficacy to reduce complications in hematopoietic stem cell transplant recipients. STUDY DESIGN AND METHODS A systematic review and meta-analysis was conducted of randomized controlled trials that assessed clinical outcomes (overall survival, transplant-related mortality, graft-versus-host disease [GVHD], veno-occlusive disease [VOD], interstitial pneumonitis, disease relapse, cytomegalovirus [CMV] infection and disease, non-CMV infection) of immunoglobulin prophylaxis versus placebo in hematopoietic stem cell transplant recipients. MEDLINE, EMBASE, EBM Reviews, and the Cochrane Central Register of Controlled Trials were searched up to June 2017. Quality of included studies and outcomes were evaluated via Risk of Bias assessment and Grading of Recommendations, Assessment, Development and Evaluation criteria, respectively. RESULTS Of 899 citations screened, 27 studies (n = 3934) were included. Immunoglobulin prophylaxis had no impact on survival (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.88-1.01; 11 studies, n = 1962) but decreased risk of acute GVHD (RR, 0.78; 95% CI, 0.65-0.94; eight studies, n = 1097) and CMV disease (RR, 0.52; 95% CI, 0.28-0.97; two studies, n = 167). Meta-analysis revealed increased risk of VOD (RR, 3.04; 95% CI, 1.10-8.41; three studies, n = 384) and disease relapse (RR, 1.26; 95% CI, 1.07-1.49; seven studies, n = 1647). Other outcomes were small in sample size or nonsignificant. Results should be interpreted cautiously given the low quality of studies and evidence of outcomes. CONCLUSION Immunoglobulin prophylaxis did not have a significant effect on survival. Positive clinical effects were shown for acute GVHD and CMV disease and negative effects against VOD and disease relapse. No studies examined the effect of immunoglobulin treatment in hypogammaglobulinemic patients despite current guidelines, warranting further studies in this population.
3.
Dose adjustment of immunosuppressants during co-administration of posaconazole: a systematic review
Fu, C., Chen, J., Xu, Y., Wu, D.
Clinical and investigative medicine. Medecine clinique et experimentale. 2018;41(1):E5-e15
Abstract
PURPOSE The purpose of this retrospective study was to analyze the dose adjustment of immunosuppressants (cyclosporine, tacrolimus and sirolimus) for the patients with allogeneic hematopoietic stem cell and solid-organ (heart/lung) transplantation during co-administration of posaconazole. METHODS MEDLINE, EMBASE and Cochrane Library were searched from January 1, 2000 to June 30, 2017 for clinical reports of patients who received allogeneic hematopoietic stem cell and organ transplantation and were co-administered posaconazole and immunosuppressants (cyclosporine, tacrolimus or sirolimus). RESULTS Seven studies were included in the systematic review with a total of 215 patients. Five studies involved hematopoietic stem cell transplant, one heart transplant and one lung transplant. In general, the co-administration of posaconazole with sirolimus, tacrolimus or cyclosporine necessitated immunosuppressant dose reductions to maintain the levels of the drug in the optimal therapeutic range. Reported dose reductions were 50%-68% for sirolimus, 75% for tacrolimus and 14%-49% for cyclosporine. The findings were similar for hematopoietic stem cell, heart or lung transplantation studies. CONCLUSION Our findings indicate that, when posaconazole is co-administered, the dosage of sirolimus and tacrolimus should be reduced by 60%-70% and for cyclosporine and by 30%-40% following allogeneic hematopoietic stem cell and solid-organ transplantation.