| Objective:Invasive fungal infections are a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation(allo-HSCT). During the past2decades, changes in transplantation practices and strategies to diagnose and treat IFI have likely impacted the epidemiology of IFI. Polymorphism of genes, which take part in the allogeneic immune response after allo-HSCT, lead to allograft immunoreactivity differences between individuals. It also may affect IFI after transplantation.The risk of recurrence of fungal infection following allo-HSCT in patients with a previous history of IFI is high, effective secondary prophylaxis of IFI for patients undergoing allo-HSCT might significantly improve outcomes, including reduced transplant-related mortality. Nevertheless, lack of data from well designed prospective studies leaves questions such as the optimal treatment or duration of treatment unsettled.We retrospectively analyzed the incidence of IFI after allo-HSCT to summarize the characteristics of the epidemiology of IFI, analysis of risk factor for IFI, look for related factors may predict IFI from gene level, and observe the safety and efficacy of secondary prophylaxis of IFI for patients undergoing allo-HSCT. The aim of the study is to reduce the incidence rate of IFI after allo-HSCT transplantation and improve the outcome of patients with allo-HSCT. Part1Risk Factors and Epidemiology of Invasive Fungal Infection in allogeneic hematopoietic stem cell transplantationMethods:We analyzed allo-HSCT recipients with a proven or probable IFI at our hospital during the period November1998through December2009. We summarized the incidence of IFI after HSCT, pathogen distribution, Univariate and multivariable analyses were used to evaluate the risk factors.Results:A total of408allo-HSCT recipients were included in this study. The patients included251males and157females with a median age of28years (age range,8-52years), the median follow-up time was28months (1-145months).92(22.5%) patients with a proven or probable IFI after allo-HSCT(4patients were proven,88patients were probable). The cumulative incidence rate of IFI for100days,6months and1year was6.83%,12.79%,20.48%respectively. According to the time after allo-HSCT,27patients with early IFI (29.35%),65patients with late IFI (70.65%), of which43cases occurred in the+180days after allo-HSCT(66.15%). Candida is the most common pathogen of early IFI. Mould is the most common pathogen of late IFI. IFI was significantly associated with survival (P＜0.001).Multivariable analyses showed that previous history of IFI, HLA mismatched, neutrophil＜0.5×109/L more than2weeks, serious aGVHD as risk factors of early IFI after allo-HSCT, and previous history of IFI, treated with corticosteroids, CMV disease and cGVHD as risk factors of late IFI after allo-HSCT.Conclusion:The results indicate that IFI after allo-HSCT was was significantly associated with survival. The distribution of pathogens and risk factors in different period after allo-HSCT is differences. According to characteristic of IFI after allo-HSCT, the importance of the optimal treatment strategies should be emphasized. Part2Relationship between Gene Polymorphism of Recipient/Donor Immune Pathway and Invasive Fungal Infection after Allogeneic Hematopoietic Stem Cell TransplantationMethods:We analyzed allo-HSCT recipients at our center during the period January2001through March2009. We analysis gene polymorphism of innate immune gene TLRs among240pairs of specimens of recipients and donors, in order to find out IFI individual difference and high risk genotype of IFI after transplantation.Results:There were99patients (41.2%) occured IFI after allo-HSCT. Hematological malignant diseases, serious acute GVHD, and extensive chronic GVHD were risk factor for IFI after allo-HSCT. Univariate analysis of the relationship between risk factors of IFI after allO-HSCT and the TLRs gene polymorphism, we found that in the10SNP loci in5TLRs, two polymorphisms of TLR8gene,(+1A/G, rs3764880;+354C/T, rs2159377) effect the incidence of IFI after allo-HSCT. Other gene polymorphism of TLRs(TLR1,TLR2,TLR3, TLR9) had no significant effects on the risk of IFI after allo-HSCT.Conclusion:The study of the relationship between the gene polymorphism of natural immune molecule TLRs and the risk factors after allo-HSCT showed that TLR8genotype of donor stem cell significantly influenced the incidence of IFI after allo-HSCT at the first time. It provide the evidence to establishment a fungal infection index system, which based on risk stratification of genetic background before transplantation of donors and recipients stem cell, and provide basis for selection of unrelated donor and prevention and treatment of IFIPart3Secondary Prophylaxis of Invasive Fungal Infection in Allogeneic Hematopoietic Stem Cell Transplantation recipientsMethods:We analyzed allo-HSCT recipients at our center from2008to2009. The patients with previous proven or probable IFI treated with Itraconazole as secondary antifungal prophylaxis in allo-HSCT during agranulocytosis phase, and to evaluate its efficacy and safety.Results:A total of125allo-HSCT recipients were included in this study. The patients included72males and53females with a median age of25years (age range,9-48years), the median follow-up time was19.2months (1-39.5months).29patients (23.2%) with a proven or probable IFI after allo-HSCT(1cases were proven,28cases were probable). According to the time after allo-HSCT, there were6patients of early IFI and23patiemts of late IFI, including16cases of IFI occurred in180days after HSCT. The cumulative incidence rate of IFI for100days,6months andl year was4.96%,11.08%,21.40%respectively.The incidence of early IFI and mortality were significantly lower than historical controls (P＜0.05).Conclusion:This study shows that secondary prophylaxis for patients with previous proven or probable IFI can obviously reduce the incidence of IFI during agranulocytosis phase after allo-HSCT. The prevention strategies of late IFI should plan new attempt. |
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