El-Cheikh J, Venton G, Crocchiolo R, Fürst S, Faucher C, Granata A, Oudin C, Coso D, Bouabdallah R, Vey N, Duran S, Fougereau E, Berger P, Chabannon C, Blaise D
1] Unité de Transplantation et de Thérapie Cellulaire (U2T), Institut Paoli-Calmettes, Marseille, France [2] Département d'Onco-Hématologie, Institut Paoli-Calmettes, Marseille, France.
Bone Marrow Transplant. 2013 Nov;48(11):1472-7. doi: 10.1038/bmt.2013.87. Epub 2013 Jun 10.
Invasive fungal infections (IFIs) such as candidiasis and mold infections have caused significant morbidity and mortality among immunocompromised patients in recent years. Micafungin, a new echinocandin, inhibits fungal cell wall β-glucan synthesis, with potent activity against most species of Candida and Aspergillus. The aim of this observational study was to investigate the efficacy and safety of micafungin in prophylaxis of IFIs in 26 high-risk adult patients with various hematological diseases receiving haplo-identical Allo-SCT. Only two patients had a history of possible aspergillosis before transplant treated by voriconazole. The patients received a median of four lines (2-7) of treatment before Allo-SCT. Thirteen patients (50%) received at least one prior Auto-SCT; and eight patients (31%) received a previous Allo-SCT. Patients received a median of 29 infusions (range, 15-85) of micafungin (50 mg/day i.v. as a 1-h infusion). The treatment was initiated at the beginning of the transplant conditioning regimen until the hospital discharge. None of our patients discontinued the treatment for drug-related adverse events. Micafungin was not associated with any hepatotoxicity. Only one patient (4%) discontinued the treatment because of early disease progression. In all patients no Candida and/or Aspergillus species was documented after 3 and 6 months from transplant. None of our patients presented a positive galactomannan antigenemia >0.5. Nine patients (35%) presented a CMV reactivation. Four patients presented an acute GVHD grade II and two patients presented a chronic GVHD. The median follow-up was 11 months (3-23). At the last follow-up, there were 20 patients (77%) who were alive; four patients (12%) died because of disease progression and two patients because of graft failure. Micafungin has a good safety and tolerability profile, with an efficacy in preventing IFI in this high-risk population. Our data provide support for an efficacy study in a prophylaxis setting, but prospective and comparative clinical trials using micafungin are urgently needed to define the role of this drug in prophylaxis after haplo-identical Allo-SCT.
近年来,侵袭性真菌感染(IFI),如念珠菌病和霉菌感染,在免疫功能低下的患者中已导致显著的发病率和死亡率。米卡芬净是一种新型棘白菌素,可抑制真菌细胞壁β-葡聚糖合成,对大多数念珠菌和曲霉菌具有强大活性。本观察性研究的目的是调查米卡芬净在26例接受单倍体相合异基因造血干细胞移植(allo-SCT)的患有各种血液系统疾病的高危成年患者中预防IFI的疗效和安全性。只有两名患者在移植前有过可能的曲霉病病史,曾接受伏立康唑治疗。患者在allo-SCT前接受的治疗中位数为4个疗程(2 - 7个疗程)。13例患者(50%)至少接受过一次自体造血干细胞移植(auto-SCT);8例患者(31%)接受过一次异基因造血干细胞移植。患者接受米卡芬净的输注中位数为29次(范围为15 - 85次)(50mg/天静脉输注,输注1小时)。治疗从移植预处理方案开始时启动,直至出院。我们的患者中没有因药物相关不良事件而停药的。米卡芬净未引起任何肝毒性。只有一名患者(4%)因疾病早期进展而停药。在所有患者中,移植后3个月和6个月均未记录到念珠菌和/或曲霉菌种。我们的患者中没有半乳甘露聚糖抗原血症>0.5阳性的。9例患者(35%)出现巨细胞病毒(CMV)再激活。4例患者出现急性移植物抗宿主病(GVHD)Ⅱ级,2例患者出现慢性GVHD。中位随访时间为11个月(3 - 23个月)。在最后一次随访时,有20例患者(77%)存活;4例患者(12%)因疾病进展死亡,2例患者因移植物失败死亡。米卡芬净具有良好的安全性和耐受性,在这一高危人群中预防IFI有效。我们的数据为预防性研究中的疗效研究提供了支持,但迫切需要进行使用米卡芬净的前瞻性和比较性临床试验,以确定该药物在单倍体相合allo-SCT后预防中的作用。