0
selected
-
1.
Real-world assessment of the effectiveness of posaconazole for the prophylaxis and treatment of invasive fungal infections in hematological patients: A retrospective observational study
Chen, X., Wang, J., Wang, S., Jin, J., Li, J., Gao, S., Li, J., Li, J., Liu, Q., Hu, Y., et al
Medicine. 2021;100(30):e26772
-
-
Free full text
-
Abstract
The aim of the study was to analyze the efficacy of posaconazole for the prophylaxis and treatment of invasive fungal diseases (IFDs) in patients with hematological malignancies.In this retrospective observational multi-center study, 762 patients from 25 Chinese hematological centers were enrolled. Inclusion criteria were patients with hematological malignancy or they had undergone hematopoietic stem cell transplantation and received at least 1 dose of posaconazole. The primary endpoints were the observation of breakthrough rates and the clinical efficacy of posaconazole prophylaxis. The secondary endpoint was the efficacy of posaconazole for the treatment of IFDs.Of the 762 enrolled patients, 456 (59.8%) were prescribed posaconazole prophylactically while 243 (31.9%) received posaconazole as an IFD treatment (12 proven, 61 probable, 109 possible, and 61 unclassified IFD cases) for ≥7 days. The overall IFD breakthrough rate (probable cases) for the ≥4 days prophylactic treatment (n = 445) group was 1.6% (95% Cl: 0.6%-3.2%), with breakthrough rates of 2.6% for acute myeloid leukemia/myelodysplastic syndrome patients undergoing chemotherapy and 2.2% for hematopoietic stem cell transplantation patients. For primary antifungal prophylaxis, the breakthrough rate was 1.9% and for secondary antifungal prophylaxis 0%. The overall effective IFD remission rate of patients treated for ≥7 days with posaconazole was 56.0% and the effective remission rate of proven/probable/possible IFD cases was 59.3%. The effective remission rate of posaconazole as salvage therapy was 50% (95% CI: 32.4%-67.6%) including 75% (CI: 19.4%-99.4%) for Aspergillus infections.The present retrospective study confirmed posaconazole as IFD prophylaxis and medication for hematological malignancy patients undergoing various treatments in China.
-
2.
Clinical risk score for predicting invasive fungal disease after allogeneic hematopoietic stem cell transplantation: Analysis of the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study
Sun, Y., Hu, J., Huang, H., Chen, J., Li, J., Ma, J., Li, J., Liang, Y., Wang, J., Li, Y., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2021;:e13611
Abstract
BACKGROUND AND OBJECTIVE Invasive fungal disease (IFD) is associated with a high mortality for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed not only to develop a proven/probable IFD risk-scoring model but to identify high-risk populations that would benefit from anti-fungal prophylaxis. METHODS Data from the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study were retrieved, and all patients (n=1053) undergoing allo-HSCT were randomly divided into the training set (n=685) for model development and the validation set (n=368) for model verification. A weighted risk score for proven or probable IFD was established through multivariate logistic regression analysis. RESULTS The study population had a mean age of 28.95 years and the majority underwent myeloablative transplantation in complete remission 1 (53.4%). Five risk factors of IFD were identified, namely neutropenia lasting longer than 14 days, corticosteroid use, diabetes, haploidentical donor, and unrelated donor. Based on the risk score for IFD, the patients were categorized into three groups: low risk (score 0-4, 1.5%-4.0%), intermediate risk (score 5-8, 9.8%), and high risk (score>8, 24.7%-14.0%). Anti-fungal prophylaxis may provide benefits for patients with intermediate (8.5% vs. 18.5%, P=0.0085) or high risk (19.4% vs. 30.8%, P=0.4651) but not low risk (2.1% vs. 3.8%, P=0.6136) of IFD. CONCLUSION A practical weighted risk score for IFD in patients receiving allo-HSCT was established, which can aid decision-making regarding administration of anti-fungal prophylaxis.
-
3.
Fluconazole is as effective as other anti-mold agents in preventing early invasive fungal disease after allogeneic stem cell transplantation: assessment of antifungal therapy in haematological disease in China
Sun, Y., Hu, J., Huang, H., Chen, J., Li, J., Ma, J., Li, J., Liang, Y., Wang, J., Li, Y., et al
Translational cancer research. 2020;9(11):6900-6911
Abstract
BACKGROUND The introduction of mold-active antifungal drugs has led clinicians to reconsider the use of fluconazole for preventing invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study of recipients of allo-HSCT, we evaluated the effects of different antifungal prophylaxes on the incidence of IFD at different times after transplantation. METHODS Among the 1,401 patients registered in the prospective China Assessment of Antifungal Therapy in Haematological Disease (CAESAR) study database, there were 661 eligible patients who received primary antifungal prophylaxis. The incidence of IFD at different times after transplantation (early, late, and very late) and overall survival were compared for patients who received different drugs. RESULTS The overall incidence of probable IFD was 7.0% in the fluconazole group, 12.6% in the itraconazole group, 1.4% in the voriconazole group, and 5.2% in the micafungin group (P=0.0379). However, the four groups had no significant differences in early, late, or very late IFD. The risk factors associated with IFD were neutropenia for more than 14 days, age greater than 18 years, and receipt of transplantation from an alternative (unrelated and haploidentical) donor (P<0.05). Sub-group analysis of alternative donors indicated that the efficacy of fluconazole was similar to the other three drugs in preventing early IFD. CONCLUSIONS Our results suggest that the efficacy of fluconazole is similar to that of mold-active drugs in preventing early IFD in HSCT patients, even in high-risk patients receiving transplantation from alternative donors. Further prospective randomized studies are needed to confirm this conclusion.
-
4.
Efficacy of Posaconazole Prophylaxis for Fungal Disease in Hematology Patients Treated With Chemotherapy and Transplantation: An Open-Label, Prospective, Observational Study
Li, W., Xia, F., Zhou, H., Qiu, H., Wu, D., Ma, X., Sun, A.
Frontiers in microbiology. 2020;11:349
Abstract
Background: Posaconazole (PCZ) is used prophylactically to prevent invasive fungal infections (IFIs) in patients with hematological malignancies. Objective: To evaluate the cut-off serum concentration of PCZ for successful IFI prophylaxis in Chinese subjects. Patients and Methods: A total of 74 patients treated with induction chemotherapy (n = 10) and allogeneic hematopoietic stem cell transplantation (HSCT) (n = 64), who received PCZ prophylactically as an oral suspension for >7 days, were included in the study. Clinical, radiological, microbiological culture results, and treatment responses were analyzed and drug concentration assays performed. Results: The overall incidence of possible, probable, and proven IFIs was 13.5% (10/74), with five patients in the chemotherapy group and five in the HSCT group. The PCZ serum concentration in most patients (54/63) was in the range of 0.25-1.0 mug/ml, and this concentration range was significantly associated with the success rate of PCZ prophylaxis. A cut-off value of 0.47 mug/ml can be considered as an evaluation index for PCZ prophylaxis. Taking a proton pump inhibitor (PPI) would reduce the PCZ blood concentration, but not affect the IFD breakthrough point. PCZ treatment for hematopoietic malignancy or HSCT patients with a serum concentration of PCZ < 0.47 mug/ml were risk factors for PCZ prophylaxis of IFIs, determined by univariable and multivariable regression analyses. Conclusion: The serum concentration of PCZ was related to the incidence of IFIs and a serum concentration of >0.47 mug/ml is highly recommended to avoid IFIs after chemotherapy or HSCT. Clinical Trial Registration: Chinese Clinical Trial Registry: ChiCTR1900026294.
-
5.
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.
-
6.
Antifungal prophylaxis of patients undergoing allogenetic hematopoietic stem cell transplantation in China: a multicenter prospective observational study
Gao, L., Sun, Y., Meng, F., Han, M., Huang, H., Wu, D., Yu, L., Ren, H., Huang, X., Zhang, X.
Journal of hematology & oncology. 2016;9(1):97
Abstract
BACKGROUND Antifungal prophylaxis is currently regarded as the gold standard in situations with allo-genetic hematopoietic stem cell transplantation (allo-HSCT). However, the epidemiological information regarding prophylaxis of invasive fungal diseases (IFDs) is not clear in China. METHODS We report the first large-scale (1053 patients) observational study of the prophylaxis and management of IFDs among patients with allo-HSCT in China. RESULTS The incidence rates of IFD after primary antifungal prophylaxis (PAP), secondary antifungal prophylaxis (SAP), and non-prophylaxis were 22.7 vs. 38.6 vs. 68.6 %, respectively (P=0.0000). The median time from transplantation to IFD was 45 days in PAP patients, 18 days in SAP patients, and 12 days in non-prophylaxis patients. Aspergillus spp. represents the most common type of fungal infection. Independent risk factors for IFD in allo-HSCT patients with PAP were age, having human leukocyte antigen (HLA)-haploidentical or matched unrelated donor, decreased albumin levels, and the use of itraconazole as the prophylactic antifungal agent. Among SAP transplant recipients, there was no significant risk factor for IFDs. The incidence rates of overall survival (OS) in the PAP, SAP, and no prophylaxis groups were 85.07, 78.80, and 74.82, respectively (P=0.01). CONCLUSIONS This observational study indicates that prophylaxis of IFD is helpful to reduce the incidence of IFDs and improve the OS of patients after allo-HSCT.