Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study.
BACKGROUND
Recurrence of prior invasive fungal infection (relapse rate of 30-50%) limits the success of stem cell transplantation. Secondary prophylaxis could reduce disease burden and improve survival.


METHODS
A prospective, open-label, multicenter trial was conducted evaluating voriconazole (4 mg/kg/12 h intravenously or 200 mg/12 h orally) as secondary antifungal prophylaxis in allogeneic stem cell transplant recipients with previous proven or probable invasive fungal infection. Voriconazole was started 48 h or more after completion of conditioning chemotherapy and was planned to be continued for 100-150 days. Patients were followed for 12 months. The primary end-point of the study was the incidence of proven or probable invasive fungal infection.


RESULTS
Forty-five patients were enrolled, 41 of whom had acute leukemia. Previous invasive fungal infections were proven or probable aspergillosis (n=31), proven candidiasis (n=5) and other proven or probable infections (n=6); prior infection could not be confirmed in three patients. The median duration of voriconazole prophylaxis was 94 days. Eleven patients (24%) died within 12 months of transplantation, but only one due to systemic fungal disease. Three invasive fungal infections occurred post-transplant: two relapses (one candidemia and one fatal scedosporiosis) and one new zygomycosis in a patient with previous aspergillosis. The 1-year cumulative incidence of invasive fungal disease was 6.7±3.6%. Two patients were withdrawn from the study due to treatment-related adverse events (i.e. liver toxicity).


CONCLUSIONS
Voriconazole appears to be safe and effective for secondary prophylaxis of systemic fungal infection after allogeneic stem cell transplantation. The observed incidence of 6.7% (with one attributable death) is considerably lower than the relapse rate reported in historical controls, thus suggesting that voriconazole is a promising prophylactic agent in this population.
Cordonnier
Catherine
C
Service d'Hématologie Clinique, Hôpital Henri Mondor, 51 Av. Maréchal de Lattre de Tassigny, Créteil, France. carlcord@club-internet.fr
Rovira
Montserrat
M
Maertens
Johan
J
Olavarria
Eduardo
E
Faucher
Catherine
C
Bilger
Karin
K
Pigneux
Arnaud
A
Cornely
Oliver A
OA
Ullmann
Andrew J
AJ
Bofarull
Rodrigo Martino
RM
de la Cámara
Rafael
R
Weisser
Maja
M
Liakopoulou
Effie
E
Abecasis
Manuel
M
Heussel
Claus Peter
CP
Pineau
Marc
M
Ljungman
Per
P
Einsele
Hermann
H
D000328:Adult; D000368:Aged; D000935:Antifungal Agents; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000517:prevention & control*; D011743:Pyrimidines / Q000008:administration & dosage*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D065819:Voriconazole; D055815:Young Adult
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole