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The indirect effects of CMV reactivation on patients following allogeneic hematopoietic stem cell transplantation: an evidence mapping
Wu, X., Ma, X., Song, T., Liu, J., Sun, Y., Wu, D.
Annals of hematology. 2024
Abstract
Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a challenging problem, and the impact on the risk of overall mortality (OM) and non-relapse mortality (NRM) in patients following allo-HSCT is still controversial. Utilizing the evidence mapping method, we aimed to assess the effect of CMV infection on outcomes of patients post-transplantation and identify research gaps through systematic reviews (SRs) and clinical studies. PubMed, EMBASE, Web of Science, and Cochrane library databases were searched from inception until 5 July 2022 to identify relevant literature. After systematic literature screening and data extraction, evidence mapping of the effects of CMV reactivation on patients post-allo-HSCT was conducted. Three SRs and 22 clinical studies were included. In one SR, CMV reactivation was associated with an increased risk of mortality (HR 1.46; 95% CI, 1.24-1.72; Pāā¤ā0.001). In two SRs, CMV reactivation was associated with NRM. One SR reported CMV reactivation was potentially associated with significant protection against relapse in patients with acute myelocytic leukemia (AML), but no significant correlation with graft-versus-host disease (GVHD) was found. Lastly, in one SR CMV reactivation significantly increased the risk of invasive fungal disease (IFD). Most clinical articles reported that CMV reactivation increased the risk of renal dysfunction, poor graft function, re-hospitalization, and bacterial infections. CMV reactivation following allo-HSCT is associated with an increased risk of OM, NRM, IFD, and renal dysfunction, as well as a reduced risk of relapse in patients with AML.
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2.
Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review
Cho, S. Y., Ar, M. C., Machado, C. M., Wu, D., Singh, I., Sandhu, A., Demuth, D., Slavin, M.
Transplant infectious disease : an official journal of the Transplantation Society. 2023;:e14083
Abstract
BACKGROUND Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post-HCT outside of Europe and North America. METHODS The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia-Pacific, Latin America, and Middle East (search period: 1 January 2011-17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatments, refractory, resistant CMV, and burden. RESULTS Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%-61.2% (23 studies) and 2.9%-15.7% (10 studies), respectively. Recurrence occurred in 19.8%-37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV-related causes. In all countries, first-line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%-10% of recipients (five studies). Patient-reported outcomes and economic data were scarce. CONCLUSION The incidence of CMV infection and disease post-HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments.
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3.
Donor-specific antibodies and primary graft failure in allo-hematopoietic stem cell transplant: a systematic review and meta-analysis: DSA and primary graft failure in allo-HSCT
Xie, Y., Parekh, J., Tang, Z., Wu, D., Wu, X.
Transplantation and cellular therapy. 2021
Abstract
BACKGROUND With increase in the number of non-matched hematopoietic stem cell transplants (HSCT), there has been growth in evidence regarding factors affecting graft outcomes. One of the factors affecting graft outcomes that are currently being evaluated is anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs). OBJECTIVE We designed our study to analyze the clinical relevance of anti-HLA DSAs in patients who have undergone hematopoietic stem cell transplant at a population level by conducting a systematic review of existing literature. STUDY DESIGN A comprehensive search was conducted through PUBMED, Embase, Cochrane library and Web of Science from inception to January 1, 2021. A meta-analysis was performed of the association between anti-HLA DSAs and primary graft failure with further subgroup analyses. It was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS A total of 920 eligible citations were identified out of which 15 studies were included in the final meta-analyses after application of rigorous selection criteria and independent review. A total of 2436 patients were included. Patients with anti-HLA DSAs prior to HSCT had a 7.47-fold increased risk of primary graft failure compared to patients without DSA (OR 7.47, 95%CI 4.54-12.28, p<0.001; I2= 28.91%, P?=?0.1315). In subgroup and meta-regression analyses, areas, NOS, mean fluorescence intensity (MFI) cut off, primary diseases, HSCT types, graft sources, and pre-transplant desensitization did not affect the impact of anti-HLA DSAs on primary graft failure (PGF). There was no significant difference between the impact of HLA class I and II on PGF as well. CONCLUSION We conclude that prior presence of anti-HLA DSAs had negative impact on graft outcomes in patients with haploidentical and umbilical cord blood hematopoietic stem cell transplants.
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4.
Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis
Zhang, R., Zhou, M., Qi, J., Miao, W., Zhang, Z., Wu, D., Han, Y.
Frontiers in immunology. 2020;11:564647
Abstract
BACKGROUND Transplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Eculizumab has been used in the treatment of TA-TMA, and several studies have confirmed the benefit of Eculizumab in patients with TA-TMA. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Eculizumab for TA-TMA. MATERIALS AND METHODS We searched PubMed and Embase for studies on the efficacy and safety of Eculizumab in TA-TMA patients. Efficacy outcomes consisted of overall response rate (ORR), complete response rate (CRR), and survival rate at the last follow-up (SR). Safety outcomes were adverse events (AEs), including infection, sepsis, impaired liver function, infusion reactions, and death. RESULTS A total of 116 patients from six studies were subjected to meta-analysis. The pooled estimates of ORR, CRR, and SR for TA-TMA patients were 71% (95% CI: 58-82%), 32% (95% CI: 11-56%), and 52% (95% CI: 40-65%), respectively. Only one patient presented with a severe rash, and infection was the most common AEs. The main causes of death were infection and GvHD. CONCLUSION Current evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed.
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5.
Autologous stem cell transplantation for patients with viral hepatitis-induced liver cirrhosis: a systematic review and meta-analysis
Chen, B., Pang, L., Cao, H., Wu, D., Wang, Y., Tao, Y., Wang, M., Chen, E.
European journal of gastroenterology & hepatology. 2019
Abstract
BACKGROUND Recently, stem cells have been used in the treatment of viral hepatitis-induced liver cirrhosis (LC), and stem cell therapy is showing potential therapeutic effects on liver function improvement. The consensus on effects and safety of stem cell therapy has not been reached, thus it is essential for us to conduct a systematic review and meat-analysis to investigate the efficacy and safety of stem cell therapy for viral hepatitis-induced LC. MATERIALS AND METHODS Medline, Embase, SinoMed and Cochrane Library databases were searched with appropriate keywords through 5 August 2018. We included eight trials involving 467 patients. The pooled weight mean difference (WMD) and 95% confidence interval (CI) were calculated using a fixed or random effects model. Quality assessment and publication bias were also performed. The selected studies were considered for meta-analysis using RevMan V5.3. RESULTS Compared with traditional therapy group, autologous stem cell transplantation increased the level of albumin (WMD: 2.47, 95% CI: 1.05-3.90, P<0.001), but decreased the level of total bilirubin (WMD: -2.26, 95% CI: -3.61 to -0.90, P=0.001), alanine aminotransferase (WMD: -9.16, 95% CI: -16.47 to -1.85, P=0.01) and prothrombin time (WMD: -3.02, 95% CI: -4.83 to -1.22, P=0.001). Clinical symptoms such as edema, fatigue, anorexia and abdominal distention were alleviated. Model for End-Stage Liver Disease and Child-Pugh scores were decreased after stem cell therapy. Whereas, there was no statistically significant difference between two groups regarding aspartate aminotransferase, prothrombin time activity, ascites and pleural fluid. No procedure-related complications were found. CONCLUSION Autologous stem cell transplantation might have beneficial effects on patients with viral hepatitis-induced LC and is relatively safe for these patients. Further high-quality randomized controlled trials are needed.
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6.
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.