title: A prospective feasibility study of primary prophylaxis against invasive fungal disease with voriconazole following umbilical cord blood transplantation with fludarabine-based conditioning.
abstract: 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.
authors.affiliation: Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-0001, Japan, shinsuke-takagi@umin.net.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Takagi
authors.forename: Hideki
authors.initials: H
authors.lastname: Araoka
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Uchida
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Uchida
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kaji
authors.forename: Hikari
authors.initials: H
authors.lastname: Ota
authors.forename: Aya
authors.initials: A
authors.lastname: Nishida
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Masanori
authors.initials: M
authors.lastname: Tsuji
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Ito
authors.forename: Naofumi
authors.initials: N
authors.lastname: Matsuno
authors.forename: Go
authors.initials: G
authors.lastname: Yamamoto
authors.forename: Yuki
authors.initials: Y
authors.lastname: Asano-Mori
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Izutsu
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Masuoka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Wake
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Makino
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoneyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology; D006402:Hematologic Diseases / Q000150:complications / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control*; D011292:Premedication; D011446:Prospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D065819:Voriconazole / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D014740:Vidarabine; D065819:Voriconazole; C024352:fludarabine