泊沙康唑预防造血干细胞移植患者侵袭性真菌病临床观察

目的 观察泊沙康唑预防恶性血液病患者造血干细胞移植(HSCT)后侵袭性真菌病的临床效果和安全性。方法 收集我院血液科2015年3月-2016年2月HSCT 19例,2例移植前有肺部真菌病史,从预处理开始口服泊沙康唑600mg/天,至中性粒细胞恢复,之后异基因造血干细胞移植患者改为伊曲康唑或伏立康唑口服至 75天。结果 19例患者未发生突破性真菌感染,在泊沙康唑使用过程中未观察到严重毒副反应发生,到随访结束时,17例存活。结论 泊沙康唑对预防恶性血液病患者造血干细胞移植后侵袭性真菌病是安全、有效的。     

艾沙康唑与伏立康唑作为口服序贯治疗恶性血液病患者侵袭性曲霉菌病的疗效及安全性比较

目的:探究并分析比较口服艾沙康唑胶囊与伏立康唑片剂在血液病患者抗真菌口服序贯治疗的疗效及安全性。方法:回顾性分析中国医学科学院血液病医院干细胞移植中心2019年11月至2023年1月诊断为侵袭性曲霉菌病,并应用伏立康唑针剂抗真菌治疗的患者共45例。其中22例患者应用伏立康唑片口服序贯治疗,23例患者应用艾沙康唑胶囊口服序贯治疗。结果:艾沙康唑组中仅1例患者评价治疗无效,其余22例治疗有反应的患者中17例评估为完全缓解,治疗缓解率为95.65%(22/23),完全缓解率为73.91%(17/23)。伏立康唑治组的治疗缓解率为86.36%(19/22),完全缓解率为50.00%(11/22)。2组患者在治疗缓解率上差异无统计学意义,且2组患者服药期间耐受性良好。结论:应用伏立康唑针剂静脉抗真菌治疗后应用艾沙康唑胶囊口服序贯与伏立康唑片口服序贯治疗相比疗效相当,且安全性良好。     

伏立康唑治疗血液病合并侵袭性真菌病61例临床观察

目的:观察伏立康唑治疗血液病合并侵袭性真菌感染(IFD)患者的疗效。方法:回顾性分析61例伏立康唑治疗血液病合并IFD患者的临床资料。结果:足量足疗程的伏立康唑治疗血液病合并IFD的总有效率为67.2%,其中预防治疗31例中24例(77.4%)有效,经验治疗24例中13例(54.2%)有效,两者的差异无统计学意义(P0.05)。9例患者用药后出现肝功能轻度异常,2例出现皮疹,1例出现恶心呕吐,均不影响治疗。结论:足量足疗程的伏立康唑治疗血液病合并IFD患者有一定疗效,不良反应较少。     

重型再生障碍性贫血强化免疫抑制治疗中三唑类抗真菌药物与环孢素的相互作用

目的:评价重型再生障碍性贫血(SAA)患者采用强化免疫抑制治疗过程中,三唑类预防性抗真菌药物泊沙康唑和伊曲康唑对环孢素(CsA)的影响。方法:SAA患者接受抗胸腺细胞免疫球蛋白和CsA治疗,分别给予泊沙康唑或伊曲康唑口服,预防真菌感染,分析不同抗真菌药物对CsA的血药浓度影响及药物剂量调整情况,比较其不良反应及医疗费用。结果:共入组55例SAA患者,分为泊沙康唑组(POSA组)(31例)和伊曲康唑组(ITRAC组)(24例),2组患者的临床特征具有可比性。POSA组和ITRAC组分别有54.8%和66.7%的患者需要降低CsA药物剂量,ITRAC组CsA维持剂量明显低于POSA组(P0.01),肝损害发生率明显高于POSA组(70.8%vs 38.7%,P=0.018)。结论:泊沙康唑和伊曲康唑与CsA有明显相互作用,在SAA强化免疫抑制治疗中,CsA的剂量应根据合并用药的类型减量,联用泊沙康唑肝损害发生率低于联用伊曲康唑。     

伴肺部侵袭性真菌病史的血液病患者行异基因造血干细胞移植的临床分析

目的探讨血液病伴肺部侵袭性真菌病(IFD)病史患者行异基因造血干细胞移植(allo-HSCT)后其肺部IFD的复发、疗效及影响因素。方法2005年3月至2006年10月南方医科大学南方医院14例肺部IFD病史的血液病患者接受allo-HSCT,移植前经抗真菌治疗10例完全缓解(CR),4例部分缓解(PR),移植中均给予预防性抗真菌治疗。调查移植后肺部IFD的复发、疗效,IFD相关病死率,Logistic回归模型分析移植方式、移植前IFD状态、预处理方案、移植物抗宿主病(GVHD)预防方案[含抗胸腺球蛋白(ATG)和不含ATG]、供受关系、急性GVHD(aGVHD)及WBC重建对移植后肺部IFD转归的影响。结果移植后肺部IFD的复发率为71.4%(10/14),移植前10例CR患者6例复发,4例PR患者全部复发;其复发时间分别为移植后3个月内7例,4~6个月内3例;10例复发患者中9例接受抗真菌治疗后4例获CR,2例PR,3例无效(NR),总有效率为6/9;移植后IFD相关病死率为35.7%(5/14);二性霉素B、伊曲康唑及伏立康唑预防肺部IFD的复发率差异无显著性意义(P=0.122);经Logisitic回归分析未发现与移植后肺部IFD复发相关的危险因素及影响其转归的危险因素。结论肺部IFD病史不是allo-HSCT的绝对禁忌证;有肺部IFD病史的患者,其移植后IFD复发率及相关病死率高。     

卡泊芬净治疗高龄患者侵袭性真菌病29例临床分析

目的 观察卡泊芬净治疗高龄患者侵袭性真菌病(IFD)的疗效和安全性. 方法 回顾分析我院老年病房接受过卡泊芬净治疗的IFD患者的临床资料. 结果 2007年1月至2009年8月共有29例患者接受卡泊芬净治疗,且均为80岁以上高龄患者.除1例于用药当天死亡外,28例可评价疗效的患者中,痊愈13例(46.4%),显效6例(21.4%),进步3例(10.8%),无效6例(21.4%),总有效率为67.8%.13例痊愈者中,12例为念珠菌菌血症患者,1例为拟诊肺白念珠菌病患者.无效6例患者中,2例为念珠菌菌血症患者,1例为拟诊肺念珠菌病患者,3例为疑诊肺IFD患者.治疗过程中1例患者出现谷丙转氨酶升高,考虑为与用药有关的肝功能受损. 结论 卡泊芬净是治疗高龄患者侵袭性真菌病的安全有效药物.     

几种常用抗真菌药物在恶性血液病合并侵袭性真菌病中的疗效分析

目的探讨临床上常用抗真菌药物在恶性血液病合并侵袭性真菌病(IFD)患者中的总体疗效、分层诊断疗效、疗效与感染部位的关系以及常见毒副反应。方法回顾性分析2005年1月至2008年8月在中山大学附属第一医院住院的117例恶性血液病合并IFD患者的临床资料。结果伊曲康唑、伏立康唑、卡泊芬净和脂质体两性霉素B治疗的总有效率分别为69.0%(40/58)、77.4%(24/31)、64.7%(11/17)和63.6%(7/11)(P=0.726);肺部感染患者中,4种药物的有效率分别为63.0%(17/27)、85.7%(12/14)、50.0%(4/8)和62.5%(5/8)(P=0.283);在肝脾念珠菌病、真菌血症及不明部位感染患者中,各用药组患者疗效相似;6周时各组存活率分别为86.2%、87.1%、70.6%和72.7%。伊曲康唑和伏立康唑常见副反应主要为胃肠道反应和轻度低钾血症,前者副反应有胃肠道反应(12.1%)、低钾血症(20.7%),伏立康唑组个别患者出现视觉异常(9.7%)和椎体外系症状(6.4%);卡泊芬净毒副反应轻微,仅见胃肠道反应(15.4%);脂质体两性霉素B组毒副反应较常见,为寒战发热(81.8%)、低钾血症(100%)、胃肠道反应(18.2%)和肝损害(9.1%)。结论伊曲康唑、伏立康唑、卡泊芬净和脂质体两性霉素B在恶性血液病合并IFD中总体疗效、分层诊断疗效以及6周存活率相当,临床治疗可根据患者特点选择个性化用药方案。     

伏立康唑治疗血液病侵袭性真菌感染93例报道

目的观察伏立康唑治疗血液病患者并发侵袭性真菌感染(IFI)的临床疗效及安全性。方法回顾分析2006—2008年天津医科大学总医院住院的93例血液病患者并发IFI的临床表现及使用伏立康唑的疗效和不良反应。结果93例IFI患者中确诊4例(4.3%)、临床诊断76例(81.7%)、拟诊13例(14.0%)。感染部位以肺部为主(87例,占93.5%),鼻腔感染2例(2.2%),血流感染2例(2.2%)、中枢神经系统和肝脏感染各1例。G试验阳性者74例(80.0%)。22例有真菌学依据,其中念珠菌12例(54.5%),曲霉菌7例(32.0%),隐球菌1例(4.5%),其他2例(9.0%)。出现影像学改变者71例(76.3%),以磨玻璃影最多(44例),其次为多发斑片状阴影(13例),不规则多发结节高密度影5例,有晕轮征者4例,有空洞形成者2例,其他改变3例。伏立康唑静脉用药时间平均14d,序贯伏立康唑口服平均20d,总疗程约34d。93例IFI患者治疗有效71例(76.4%),疗效不佳11例(11.8%),死亡11例(11.8%)。其中拟诊组有效率84.6%,临床诊断组有效率77.6%,两者之间差异无统计学意义(P=0...     

伏立康唑治疗急性髓系白血病诱导化疗期肺部侵袭性真菌感染的疗效

目的观察伏立康唑对急性髓系白血病诱导化疗期肺部侵袭性真菌感染的临床治疗效果。方法选取该院2012年1月至2016年9月收治的40例急性髓系白血病化疗后发生肺部侵袭性真菌感染的患者作为研究对象,观察患者使用伏立康唑治疗后的临床疗效。结果治疗后患者有效率为82.5%(33/40)。其中痊愈32.5%(13/40),显效22.5%(9/40),进步27.5%(11/40),无效17.5%(7/40)。此疗效与白血病患者的性别、年龄无关,与预后分层、化疗疗效有关。结论可选择伏立康唑治疗急性髓系白血病诱导化疗后肺部真菌感染,其效果显著,经济性较高,可推广使用。     

侵袭性真菌感染患者肺泡灌洗液中半乳甘露聚糖的水平变化及临床意义

目的探讨侵袭性真菌感染患者肺泡灌洗液中半乳甘露聚糖(GM)的水平变化及临床意义。方法连续性纳入50例怀疑IFD的恶性血液病患者,25例非IFD的恶性血液病患者作为对照组。检测血清和肺泡灌洗液GM水平,利用ROC曲线分析肺泡灌洗液GM实验对IFD患者的诊断价值。通过单因素和Logistic回归分析计算OR值比较不同临床指标对于GM实验的影响。结果疑似组,拟诊组和确诊组患者肺泡灌洗液GM平均值均高于血清GM平均值(0.31±0.09 ng/ml,0.46±0.12 ng/ml,0.49±0.07 ng/ml vs.0.24±0.08 ng/ml,0.44±0.22 ng/ml,0.48±0.20 ng/ml)。阳性率方面,疑似组,拟诊组和确诊组患者肺泡灌洗液GM阳性率均高于血清GM阳性率(17.5%,33.3%,66.7%vs.3.2%,18.5%,33.3%)。ROC曲线分析示确诊组患者,确诊组+拟诊组患者以及所有患者AUC分别为0.76,0.69和0.60。抗真菌药物的使用与肺泡灌洗液GM实验阳性率密切相关(P0.05)。结论在恶性血液病患者中,肺泡灌洗液GM实验有助于对IFD的诊断。     

Comparison of invasive fungal diseases between patients with acute myeloid leukemia receiving posaconazole prophylaxis and those not receiving prophylaxis: A single-center,observational, case-control study in South Korea

Posaconazole prophylaxis is effective in decreasing the incidence of invasive fungal diseases (IFDs) in patients with acute myeloid leukemia (AML). However, the use of antifungal prophylaxis varies in real-life practice, and only a small number of studies have compared the incidence of IFDs between those receiving posaconazole prophylaxis and those without prophylaxis. We compared the clinical characteristics and outcomes of IFDs between patients with AML who received posaconazole prophylaxis and those without antifungal prophylaxis.We reviewed the medical records of adult AML patients who underwent induction chemotherapy between June 2016 and October 2019 at Asan Medical Center (Seoul, South Korea), where posaconazole prophylaxis is not administered in patients with gastrointestinal symptoms that may hinder sufficient absorption of oral prophylactic agents, and in patients with abnormal liver functions considering the possible exacerbation of adverse events. Patients who received posaconazole prophylaxis for ≥7 days were included in the prophylaxis group. Clinical characteristics and outcomes including the incidence of IFDs were compared between the 2 groups.Of the 247 patients with AML who underwent induction chemotherapy, 162 (66%) received posaconazole prophylaxis and 85 (34%) did not receive any prophylaxis. The incidence of proven/probable IFD was significantly higher in the no prophylaxis group than in the prophylaxis group (9.4% [8/85] vs 2.5% [4/162], P = .03). Of the 8 cases of IFDs in the no prophylaxis group, 7 were mold infections and 1 was invasive candidiasis. Of the 4 cases of IFDs in the prophylaxis group, 3 were mold infections and 1 was invasive candidiasis. Patients with posaconazole prophylaxis less frequently received therapeutic antifungal therapy (2.5% vs 9.4%, P = .03) and had a longer median, duration from chemotherapy to antifungal therapy compared with the no prophylaxis group (18 vs 11 days, P < .01). The rate of IFD-related mortality was similar between the 2 groups (0.6% vs 0%, P > .99).Patients with AML who received posaconazole prophylaxis had a lower incidence of breakthrough IFDs compared with those who did not receive any prophylaxis. Invasive mold infection was the most common IFD regardless of antifungal prophylaxis.     

Real-world assessment of the effectiveness of posaconazole for the prophylaxis and treatment of invasive fungal infections in hematological patients: A retrospective observational study

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.     

The incidence of invasive fungal infections in neutropenic patients with acute leukemia and myelodysplastic syndromes receiving primary antifungal prophylaxis with voriconazole

The objective of this study is to characterize the outcomes of primary antifungal prophylaxis with voriconazole in patients receiving intensive chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). We conducted a single center, retrospective, cohort study of consecutive adult patients with AML or MDS at Mayo Clinic between January 1, 2006 and July 1, 2010. The study included patients undergoing induction or first relapse combination chemotherapy who received voriconazole 200 mg orally twice daily as prophylaxis during the neutropenic phase. Patient records were evaluated until 30 days after neutrophil recovery for development of invasive fungal infection (IFI) as defined per EORTC/MSG 2008 criteria with computed tomography scans independently reviewed by a radiologist. Therapeutic drug monitoring and reasons for voriconazole discontinuation were documented. Twenty four episodes of IFI were detected among 165 consecutive patients for an overall incidence of 145 per 1000 patients. The incidence of IFI was 24, 42, and 78 per 1000 patients for proven, probable, and possible infection, respectively. Four patients developed proven IFI (n = 2 Aspergillus spp., n = 2 Rhizopus spp.). Serum voriconazole trough concentrations were available in 39 patients, and no statistically significant difference in voriconazole trough level was observed between those with versus without an IFI. Voriconazole prophylaxis was discontinued in 81 patients due to suspected IFI (n = 24), fever of unknown origin (n = 19), adverse events (n = 23), and other causes (n = 17). Voriconazole as primary IFI prophylaxis is safe and may be beneficial in AML/MDS patients receiving intensive chemotherapy. Am. J. Hematol. 88:283–288, 2013. © 2013 Wiley Periodicals, Inc.     

Primary antifungal prophylaxis with micafungin in patients with haematological malignancies: real‐life data from a retrospective single‐centre observational study

Mould‐active antifungal prophylaxis is increasingly used in patients at risk for invasive fungal disease. Between June 2011 and June 2012, one hundred patients with various haematological malignancies at risk for invasive fungal disease received primary antifungal prophylaxis with intravenous micafungin at a daily dosage of 50 mg during neutropenia. The median number of days on micafungin prophylaxis was 14 (range, 6–48 d). The incidence of proven and probable breakthrough invasive fungal diseases (bIFDs) was 6% and 3%, respectively. There were two bloodstream infections caused by yeasts or yeast‐like fungi (Candida krusei, Trichosporon asahii) in two patients during the neutropenic phase after allogeneic haematopoietic stem cell transplantation. Four proven bIFDs caused by non‐Aspergillus moulds and three cases of probable pulmonary bIFDs were documented during the neutropenic phase after induction/consolidation chemotherapy for acute leukaemia. Colonisation with Candida spp. was documented in 51% of the patients with none of the isolates being in vitro micafungin resistant. Compared to a historical control, receiving primary prophylaxis with posaconazole micafungin is at least as effective in preventing IFD. In both cohorts, bIFDs were exclusively caused by emerging pathogens with a highly preserved in vitro sensitivity to amphotericin B.     

Voriconazole as primary antifungal prophylaxis in children undergoing allo-SCT

Invasive fungal disease (IFD) causes significant morbidity and mortality among children undergoing allo-SCT. In this prospective pilot study, we analyze voriconazole as primary antifungal prophylaxis. From October 2004 to July 2010, 56 children <18 years of age were enrolled in this study. Patients received voriconazole doses of 5 mg/kg per 12 h (n=23) or 7 mg/kg per 12 h (n=33), with a limiting dose of 200 mg/12 h, from day -1 to day +75 or later in patients with active acute GVHD. Patients were followed up for IFD for 6 months. In this series, 37 (66.1%) patients successfully completed treatment (85.7% during neutropenic period) without empirical or preemptive antifungal therapy, adverse effects or IFD. Nine (16.1%) children needed preemptive (n=2) or empirical (n=7) antifungal therapy, and one (1.8%) of them developed a fatal probable IFD during the study period. A total of 10 (17.8%) children developed adverse effects related to voriconazole prophylaxis, leading to definitive withdrawal on median day 26.5 (in 7 patients after granulocytic recovery). The most frequent adverse effect was persistent elevation of hepatic enzymes in seven (12.5%) children. There were no differences between doses of 5 and 7 mg/kg per 12 h. Our results suggest that voriconazole can be safely used as primary antifungal prophylaxis in children undergoing allo-SCT.     

The prophylactic effect of itraconazole capsules and fluconazole capsules for systemic fungal infections in patients with acute myeloid leukemia and myelodysplastic syndromes: a japanese multicenter randomized, controlled study

We performed a randomized, controlled study comparing the prophylactic effects of capsule forms of fluconazole (n = 110) and itraconazole (n = 108) in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) during and after chemotherapy. There were 4 cases with possible systemic fungal infection in the itraconazole group, and there were 8 possible and 3 probable cases in the fluconazole group. Adverse events did not significantly differ in the 2 groups. In patients with MDS or in the remission-induction phase of chemotherapy, the numbers of cases with probable or possible infections were lower in the itraconazole group than in the fluconazole group, whereas no difference was seen in patients with AML or in the consolidation phase of therapy. In patients with neutrophil counts of >0.1 x 10(9)/L lasting for more than 4 weeks, the frequency of infection in the fluconazole group (5 of 9 patients) was significantly higher than in the itraconazole group (0 of 7 patients; P = .03). Our results suggest that both drugs were well tolerated in patients with AML or MDS who received chemotherapy and that the efficacy of itraconazole for prophylaxis against systemic fungal disease is not inferior to that of fluconazole.     

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience

Background

Posaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia.

Design and Methods

The impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs.

Results

Proven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs.

Conclusions

Primary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a “real-life” scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous.     

Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period

Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs. 8%, P=0.011), premature discontinuations (46% vs. 22% P<0.001) and empiric antifungal treatment (31% vs. 8.5%, P<0.001). Microbiologically confirmed infections were molds. Posaconazole compared to other drugs was associated with fewer courses requiring computed-tomography (43% vs. 26%, P<0.001). Adoption of voriconazole/posaconazole has decreased invasive fungal disease incidence, empiric antifungal treatment and for posaconazole, computed-tomography demand, with effectiveness of posaconazole comparable to clinical trial experience.     

A Single Center Experience for Antifungal Prophylaxis in Patients with Acute Myelogenous Leukemia

We aimed to provide real-life information about the effectivity of different types of primary antifungal prophylaxis (AFP) in patients with acute myeloid leukemia (AML). Records of AML patients who received remission-induction chemotherapy between June 2010 and February 2013 were retrospectively reviewed. A total of 85 AML remission-induction chemotherapy cycles were identified in 80 patients. Fluconazole prophylaxis (FP) was administered in 29 cycles, and posaconazole prophylaxis was given in 56 cycles. Failure in the AFP was observed in 45 (57.9 %) out of 85 cycles. Any type of invasive fungal diseases were detected in 15 (26.8 %) out of 56 cycles receiving posaconazole and 15 (51.7 %) out of 29 cycles receiving fluconazole (p = 0.023). Relapsing or refractory AML, longer duration of neutropenia and FP were more common in patients with AFP failure. Multivariate logistic regression analysis showed that type of AFP (odds ratio (OR) 3.63; 95 % confidence interval (CI) 1.19–11.07), presence of neutropenia longer than 21 days (OR 3.96; 95 % CI 1.36–11.46), and refractory or relapsing AML (OR 6.09; 95 % CI 2.09–17.73) were independent factors associated with failure of AFP. We observed superiority of posaconazole on fluconazole in the prophylaxis of AML patients receiving remission-induction chemotherapy.     

A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning

Despite the recent introduction of a new class of anti-Aspergillus agents, no standard regimen for the prevention of invasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation has been shown to be superior to fluconazole. The present prospective, single-arm study investigated the feasibility of voriconazole (VOR) administration as primary prophylaxis in 52 recipients of umbilical cord blood transplantation (CBT) with fludarabine-based conditioning, who had no previous IFD episodes. Proven or probable IFD was determined using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group, and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria were considered as breakthrough infections. VOR was administered as prophylaxis for a total of 6884 patient-days following CBT. The mean duration of VOR administration after transplantation was 132 days (range, 1–769); 44 patients (85 %) had advanced disease, 15 (29 %) had a history of allogeneic HSCT, and 29 (56 %) received systemic corticosteroid therapy for allogeneic immune-mediated complications. Under the prophylaxis with VOR, one patient developed probable invasive aspergillosis on day 71, and the cumulative incidence of IFD was 4.5 % at day 180. None of the patients developed breakthrough candida or zygomycetes infections. Under the extensive therapeutic dose monitoring, VOR was safely administered with a calcineurin inhibitor and was well tolerated. These results suggest that VOR represents a feasible primary prophylactic agent for IFD after CBT with fludarabine-based conditioning.