Influence of Pretreatment with Amphotericin B on Treatement-Related Mortality (TRM) Following Allogeneic Stem Cell Transplantations.

Conventional amphotericin B (C-AMB) is one of the most frequently used antifungal first line agents in patients with hematological malignancies diagnosed to have invasive fungal infections or persistent neutropenic fever despite of its well documented adverse effect profile. To evaluate the influence of pretreatment with C-AMB on the outcome of allogeneic HSCT, a retrospective analysis including 270 consecutive allogeneic HSCT between 1/2002 and 12/2003 at out institution was performed. Median patient age was 42 years, female to male ratio 46/51 and CMV positivity 83 %. Diagnosis was AML (n=90), ALL (n=72), CML (n=45), MDS (n=21), NHL (n=14), MM (n=8) or micellaneous (n=20). Sixty percent (164/270) of patients were in early, the remainders in advanced disease stages. Conditioning therapy was TBI or chemotherapy in 237 and 33 patients, respectively. Donors were identical siblings (n=110), non-identical family members (n=3), matched unrelated (n=116) or mismatched unrelated (n=41). Pretreatment with antimycotics was reported in 74 cases (C-AMB, n=73; voriconazole, n=1) for FUO (n=23), not specified fungal pneumonia (n=23), pneumonia due to aspergillus sp.(n=18), hepatosplenic candidiasis (n=6), fungemia (n=3), and IFI by scedosporium prolificans (n=1). A Cox regression model was used to test C-AMB pretreatment as an independent risk factor on TRM. Age in decades, disease stage, preceding neutropenia, renal impairment (creatinine > 1mg/dl) was also included. Only previous treatment with C-AMB (p=0.001; RR 3), and advanced disease stage (p=0.008; RR2,5) remaind statistically significant. Subsequently, to identify patients at increased risk, we defined following strata: 1. patients without previous neutropenia; 2. patients with previous neutropenia; 3. patients with C-AMB pretreatment, creatinin < 1,0 mg%; 4. patients with C-AMB pretreatment and creatinin > 1,0mg%; 5. patients with renal impairment for other causes; 6. patients with renal impairment or C-AMB pretreatment and antimycotic therapy during transplant procedure. TRM was 3.2%, 5.43%, 19.57%, 26.67%, 29.63% and 24.14%, respectively. We conclude that patients being pretreated with conventional C-AMB have an increased independent risk for TRM (RR 4; p<0.001).