title: Antimycotic therapy with liposomal amphotericin-B for patients undergoing bone marrow or peripheral blood stem cell transplantation.
abstract: Suspected deep or systemic mycosis in patients undergoing high-dose therapy and autologous or allogeneic bone marrow transplantation (BMT) requires an immediate systemic antimycotic therapy. Intravenous therapy with the standard drug conventional amphotericin-B is associated with severe adverse effects like nephrotoxicity and chills. Furthermore, BMT patients often receive other potential nephrotoxic drugs such as CsA or virustatics. In this study, we report 74 BMT-patients treated with liposomal amphotericin-B for culture-documented aspergillosis (n = 5) or candidiasis (n = 6), or for serologically (n = 35) or clinically suspected mycosis or as prophylaxis (n = 2). Therapy was initiated with a median dose of 2.8 (0.64-5.09) mg/kg body-weight and continued for 13 (1-55) days. The drug was excellently tolerated and only in one was therapy stopped due to severe chills and fever. Severe organ impairment was not observed under therapy with liposomal amphotericin-B. Creatinine decreased in five patients after an increase under preceding therapy with the conventional formulation. Influence of liposomal amphotericin-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, veno-occlusive disease (VOD), and graft-versus-host disease (GvHD). 10/11 culture-positive patients died from aspergillosis (5/5) or candidiasis (5/6), but in 9/11 of these subjects the immunity was additionally compromised by GvHD, steroid therapy, and VOD. Liposomal amphotericin-B was effective in preventing relapse of systemic mycosis in 10/12 patients with a history of aspergillosis (n = 11) or candidiasis (n = 1). We conclude, that favourable toxicity of liposomal amphotericin-B should encourage dose escalation studies of liposomal amphotericin-B randomised against the conventional formulation and that the comparison of patients undergoing BMT with patients under standard chemotherapy might be difficult because of additional risk factors of the BMT-patients.
authors.affiliation: Department of Oncology/Haematology, University-Hospital Eppendorf, Hamburg, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Krüger
authors.forename: M
authors.initials: M
authors.lastname: Stockschläder
authors.forename: I
authors.initials: I
authors.lastname: Sobottka
authors.forename: R
authors.initials: R
authors.lastname: Betker
authors.forename: M
authors.initials: M
authors.lastname: De Wit
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.forename: J
authors.initials: J
authors.lastname: Grimm
authors.forename: M
authors.initials: M
authors.lastname: Arland
authors.forename: W
authors.initials: W
authors.lastname: Fiedler
authors.forename: R
authors.initials: R
authors.lastname: Erttmann
authors.forename: A R
authors.initials: AR
authors.lastname: Zander
mesh_terms: D000293:Adolescent; D000328:Adult; D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D000666:Amphotericin B