Analysis Of The Efficacy And Safety Of Primary Antifungal Prophylaxis Of IFD After Allogeneic Hematopoietic Stem Cell Transplantation

Objective:Exploring economical and effective primary prevention strategies for IFD after allogeneic hematopoietic stem cell transplantation.Methods:A retrospective analysis of allogeneic hematopoietic stem cell transplant patients who met the screening conditions from January 2014 to September 2017 at the Department of Hematology,First Affiliated Hospital of Jilin University.According to the difference of primary prevention and early medication,patients was divided into fluconazole prophylaxis group,micafungin prophylaxis group and posaconazole prophylaxis group.After the recovery of grain defects,follow-up preventive medications were adjusted according to whether or not GVHD occurred.Follow-up to the patient’s death or cut-off date(end-to-end for the lost follow-up patient).Clinical characteristics such as gender,age,disease type,remission status,transplantation type,graft source,and pretreatment regimen,cell engraftment after transplantation,IFD occurrence,graft-versus-host disease and other transplant related complications were collected,the adverse reactions and discontinuation were recorded.After comparison and analysis,IFD breakthrough rate,total survival,event-free survival and adverse drug reactions in different drug groups were evaluated.Results:A total of 105 allo-HSCH patients who met the inclusion criteria were screened.The number of patients treated with fluconazole prophylaxis,micafungin prophylaxis,and posaconazole prophylaxis was 23,60,and 22,respectively.Compared with the general characteristics of the three groups,gender,age,underlying disease,and disease status were not statistically significant.The median follow-up time was compared with fluconazole group 9.7 months,micafungin group28.82 months,posaconazole group 15.23 months,and the follow-up time of fluconazole was shorter than the other two groups,with statistical significance(P <0.05).The age and type of transplantation constituted three groups.Posaconazole group had higher age and higher haploid ratio than the other two groups(average age: 34.77 years in posaconazole group,28.13 years in fluconazole group,micafon)The net group was28.22 years old;haploid proportions were 81.82% in the posaconazole group,60.87% in the fluconazole group,and 80% in the micafungin group,but not statistically significant.There was no statistically significant difference between the three groups after implantation.Comparing transplantation-related complications,the occurrence of III-IV a-GVHD in the posaconazole group was higher than that in the fluconazole group,and P<0.05,statistically significant,and there was no difference in other transplant-related complications among the three groups.According to the latest revised guideline for the diagnosis and treatment of invasive fungal disease(IFD)in 2017,IFD diagnosis is divided into confirmed,clinically diagnosed,suspected and undefined.This study was conducted as a breakthrough in the IFD for suspected and suspected diagnoses.In the fluconazole group,1 case(4.3%)was diagnosed,5 cases(21.74%)were diagnosed,2 cases(3.3%)were diagnosed in the micafungin group,6 cases(10%)were diagnosed,and the posaconazole group was included.One case(4.5%)was clinically diagnosed and 0 cases were diagnosed.No IFD was diagnosed in all three groups.As of the follow-up period(April 18,2018),cumulative rates of100-day cumulative fungal infection in the fluconazole group,micafungin group,and posaconazole group were 23% in the fluconazole group and micafungin group.5.0% in the posaconazole group 4.5%;the cumulative incidence of fungi for 180 days was 23% in the fluconazole group,5.0%in the micafungin group,and 4.5% in the posaconazole group;the cumulative incidence of the fungi for 1 year was: 29.8% of the fluconazole group,13.8% of the micafungin group,and 4.5% of the posaconazole group.In the three groups,the cumulative incidence of fungal infection in the micafungin and posaconazole groups was lower than that in the fluconazole group.Among them,the posaconazole group was lower than the fluconazole group in the cumulative fungal incidence rate,and P = 0.049,statistically significant,while the micafungin group was higher than the fluconazole group,posaconazole,and micafungin group had a decrease in IFD trends but not statistically significant.The recurrence of the three groups was compared,there was no recurrence in the fluconazole group,11 in the micafungin group,and 4 in the posaconazole group.Comparison of deaths,fluconazole group died in6 cases,are all related to death,including IFD related death in 1 case,related mortality was 16.7%(1/6).There were 16 deaths in the micafungin group,10 relapse-related deaths,6 graft-related deaths,and no IFD-related deaths.There were 8 deaths in the posaconazole group,1recurrence-related death,7 graft-related deaths,and no IFD-related deaths.Comparison of the three groups of data found that the recurrence rate was lower in the fluconazole group than in the other two groups,and consideration may be related to the shorter follow-up time in this group of patients.Comparison of overall survival and event-free incidence in the three groups,1-year overall survival rate: fluconazole group: 71.7%,micafungin group: 81.7%,posaconazole group: 62.0%;3-year overall survival rate: fluorine Conazole group: 71.7%,micafungin group: 74.7%,posaconazole group: 62.0%.1 year event free survival rate: fluconazole group: 73.7%,micafungin group: 84.4%,posaconazole group: 84.8%;3year event free survival rate: fluconazole group: 61.5%,Mika Fenjing group: 69.2%,posaconazole group: 59.4%.There were no statistically significant differences between the three groups.In the micafungin,posaconazole,and fluconazole groups,the adverse drug reactions(including gastrointestinal symptoms and hepatic impairment)were small,and there was no statistically significant difference between the three groups.There were no cases of discontinuation due to adverse reactions in all three groups and the tolerance of patient was good.Conclusion:1.Fluconazole,micafungin,and posaconazole are effective prophylactics for IFD in patients undergoing hematopoietic stem cell transplantation.2.Posaconazole group compared with fluconazole group can effectively reduce the incidence of IFD,micafungin group compared with fluconazole group,posaconazole group compared with micafungin group have a tendency to reduce the incidence of IFD.3.Patients with haplotypes and GVHD transplants may be prevented by early application of Aspergillus coated drugs,which may reduce the incidence of IFD.4.Early prevention of high-risk patients with posaconazole or micafungin may be an effective and economical preventive measure when mitogen-free replacement is followed by fluconazole prophylaxis.5.The adverse reactions of micafungin and posaconazole were less,and patients were better tolerated.