Prophylaxis of invasive aspergillosis with voriconazole or caspofungin during building work in patients with acute leukemia

Background Invasive aspergillosis is a common life-threatening infection in patients with acute leukemia. The presence of building work near to hospital wards in which these patients are cared for is an important risk factor for the development of invasive aspergillosis. This study assessed the impact of voriconazole or caspofungin prophylaxis in patients undergoing induction chemotherapy for acute leukemia in a hematology unit exposed to building work. Design and Methods This retrospective cohort study was carried out between June 2003 and January 2006 during which building work exposed patients to a persistently increased risk of invasive aspergillosis. This study compared the cumulative incidence of invasive aspergillosis in patients who did or did not receive primary antifungal prophylaxis. The diagnosis of invasive aspergillosis was based on the European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria. Results Two-hundred and fifty-seven patients (213 with acute myeloid leukemia, 44 with acute lymphocytic leukemia) were included. The mean age of the patients was 54 years and the mean duration of their neutropenia was 21 days. Eighty-eight received antifungal prophylaxis, most with voriconazole (n=74). The characteristics of the patients who did or did not receive prophylaxis were similar except that pulmonary antecedents (chronic bronchopulmonary disorders or active tobacco use) were more frequent in the prophylaxis group. Invasive aspergillosis was diagnosed in 21 patients (12%) in the non-prophylaxis group and four (4.5%) in the prophylaxis group (P=0.04). Pulmonary antecedents, neutropenia at diagnosis and acute myeloid leukemia with high-risk cytogenetics were positively correlated with invasive aspergillosis, whereas primary prophylaxis was negatively correlated. Survival was similar in both groups. No case of zygomycosis was observed. The 3-month mortality rate was 28% in patients with invasive aspergillosis. Conclusions This study suggests that antifungal prophylaxis with voriconazole could be useful in acute leukemia patients undergoing first remission-induction chemotherapy in settings in which there is a high-risk of invasive aspergillosis.

[1]  H. Dombret,et al.  Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Patricia Muñoz,et al.  Revised definitions of invasive fungal disease from 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) Consensus Group. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  B. Thiers.  Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia , 2008 .

[4]  G. Wassmer,et al.  A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML). , 2007, The Journal of infection.

[5]  J. Reiffers,et al.  Adding lomustine to idarubicin and cytarabine for induction chemotherapy in older patients with acute myeloid leukemia: the BGMT 95 trial results , 2007, Haematologica.

[6]  Philippe Broët,et al.  Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients. , 2007, Blood.

[7]  C. Lass‐Flörl,et al.  Primary antifungal prophylaxis in leukaemia patients , 2007 .

[8]  C. Heussel,et al.  Liposomal amphotericin B as initial therapy for invasive mold infection: a randomized trial comparing a high-loading dose regimen with standard dosing (AmBiLoad trial). , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  J. Perfect,et al.  Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. , 2007, The New England journal of medicine.

[10]  Peter G. Pappas,et al.  Invasive Fungal Pathogens: Current Epidemiological Trends , 2006 .

[11]  F. Lucht,et al.  Efficacy of environmental measures to decrease the risk of hospital-acquired aspergillosis in patients hospitalised in haematology wards. , 2006, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[12]  P. Gastmeier,et al.  Nosocomial aspergillosis in outbreak settings. , 2006, The Journal of hospital infection.

[13]  P. Polgreen,et al.  Incidence of invasive aspergillosis among allogeneic hematopoietic stem cell transplant patients receiving voriconazole prophylaxis. , 2006, Diagnostic microbiology and infectious disease.

[14]  H. Dombret,et al.  High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia , 2006, Leukemia.

[15]  L. Pagano,et al.  Design and Methods , 2022 .

[16]  S. Koscielny,et al.  Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[17]  Richard Sylvester,et al.  Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. , 2002, The New England journal of medicine.

[18]  C. Maslo,et al.  Epidemiology of invasive aspergillosis in France: a six-year multicentric survey in the Greater Paris area. , 2002, The Journal of hospital infection.

[19]  F. Derouin,et al.  Relationship between environmental fungal contamination and the incidence of invasive aspergillosis in haematology patients. , 2001, The Journal of hospital infection.

[20]  J. Rowe,et al.  Invasive pulmonary aspergillosis in neutropenic patients during hospital construction: Before and after chemoprophylaxis and institution of HEPA filters , 2001, American journal of hematology.

[21]  S J Lin,et al.  Aspergillosis case-fatality rate: systematic review of the literature. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  L. Mannone,et al.  Role of early diagnosis and aggressive surgery in the management of invasive pulmonary aspergillosis in neutropenic patients. , 2001, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[23]  M. Slovak,et al.  Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. , 2000, Blood.

[24]  A. van Belkum,et al.  Density and Molecular Epidemiology ofAspergillus in Air and Relationship to Outbreaks ofAspergillus Infection , 1999, Journal of Clinical Microbiology.

[25]  K. Do,et al.  Interaction of Granulocytopenia and Construction Activity as Risk Factors for Nosocomial Invasive Filamentous Fungal Disease in Patients With Hematologic Disorders , 1990, Infection Control & Hospital Epidemiology.