Sarina Barbara, Mariotti Jacopo, Bramanti Stefania, Morabito Lucio, Crocchiolo Roberto, Rimondo Andrea, Tordato Federica, Pocaterra Daria, Casari Erminia, De Philippis Chiara, Carlo-Stella Carmelo, Santoro Armando, Castagna Luca
Bone Marrow Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Italy.
Infectious Diseases Unit, Hospital Health Direction, IRCCS Istituto Clinico Humanitas, Rozzano, Italy.
Transpl Infect Dis. 2018 Aug;20(4):e12906. doi: 10.1111/tid.12906. Epub 2018 May 16.
Invasive fungal infections (IFI) represent a common side effect of allogeneic hematopoietic stem cell transplant (allo-SCT), resulting in increased non relapse mortality (NRM) and reduced overall survival (OS) rates. Seventy-five days of Fluconazole 400 mg/d represents the standard primary antifungal prophylaxis (PAP) after allo-SCT, especially for low-risk transplants. However, the ideal dosage of fluconazole has never been tested.
Here, we report the experience of our institution on 113 consecutive patients receiving an allo-SCT from a HLA identical sibling between 1999 and 2015, where PAP consisted of fluconazole 100 mg/d only during the pre-engraftment phase. At the time of transplant, all patients were considered at low-risk for mold infection according to ECIL-5 guidelines.
Cumulative incidence of possible-probable-proven IFI was 11.7%, while proven-probable (PP-IFI) occurred in 5.5% of patients by day 100 post transplant. Of note, only 1 patient developed invasive Candidiasis due to a non-albicans strain and stool-screening tests were negative for colonization by Candida albicans species. The incidence of 1-year acute and 2-year chronic graft-versus-host-disease (GVHD) was 30% and 45%, respectively. Three-year OS and 1-year NRM were 53% and 11.3%, respectively.
In summary, fungal prophylaxis with fluconazole 100 mg/d results in very low incidence of PP-IFI, GVHD and NRM in low-risk allo-SCT.
侵袭性真菌感染（IFI）是异基因造血干细胞移植（allo-SCT）的常见副作用，会导致非复发死亡率（NRM）增加和总生存率（OS）降低。氟康唑400mg/d使用75天是allo-SCT后标准的一级抗真菌预防（PAP）措施，尤其是对于低风险移植。然而，氟康唑的理想剂量从未经过测试。
在此，我们报告了本机构1999年至2015年间连续113例接受来自 HLA 相同同胞的 allo-SCT 患者的经验，其中PAP仅在植入前阶段使用100mg/d氟康唑。移植时，根据ECIL-5指南，所有患者被认为发生霉菌感染的风险较低。
可能-很可能-确诊的IFI累积发生率为11.7%，而确诊-很可能（PP-IFI）在移植后100天时发生在5.5%的患者中。值得注意的是，只有1例患者因非白色念珠菌菌株发生侵袭性念珠菌病，且粪便筛查试验显示白色念珠菌属定植为阴性。1年急性和2年慢性移植物抗宿主病（GVHD）的发生率分别为30%和45%。三年总生存率和一年非复发死亡率分别为53%和11.3%。
总之，对于低风险allo-SCT，100mg/d氟康唑进行真菌预防导致PP-IFI、GVHD和NRM的发生率非常低。
