Antimycotic therapy with liposomal amphotericin B for patients undergoing bone marrow or peripheral blood stem cell

WH Krüger, BC Rüssmann, N Kröger, N Ekopf, N Fuchs, I Sobottka, R Erttmann, H Kabisch, AR Zander


Suspected deep or systemic mycosis in high-dose therapy and autologous or allogeneic bone marrow- transplantation (BMT) patients requires an immediate systemic antimycotic therapy. Intravenous therapy with the standard drug conventional (conv) amphotericin-B (am-B) is associated with severe adverse effects like nephrotoxicity and chills. Furthermore, BMT patients receive often other potential nephrotoxic drugs such as CsA or virustatics. In this study, we report 110 BMT-patients treated with liposomal (lip) amphotericin-B for culture-documented aspergillosis (n = 7) or candidosis (n = 7), or for serologically or clinically suspected mycosis, or as prophylaxis (n = 2). Therapy was initiated with a median dose of 2.9 (0.64-5.22) mg/kg bodyweight and continued for 13 (1-61) days. The median dose at the end of therapy was 3 (1-10.5) mg/kg. The drug tolerance was excellent, only in one man therapy was stopped due to massive chills and fever. Severe organ impairment was not observed under therapy with lip am-B. Creatinine decreased in 25 patients below the base line, seven of these patients had a history of a creatinine increase under conv am-B. Influence of lip am-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, suspected or documented veno-occlusive disease (VOD), and graft-versus-host disease (GvHD). 13/14 culture-positive patients died directly or secondary from their mycoses, but in 10/14 of the culture-positive subjects, the immunity was additionally compromised by GvHD, steroid therapy, and documented or suspected VOD. The overall response rate including fever and clinical course was 51.8% (57/110, 18 not evaluable). Lip am-B was effective in preventing relapse of systemic mycosis in 15/19 patients with a history of preceding mycosis. We conclude, that favourable toxicity of lip am-B should encourage dose escalation studies of lip am-B randomised against the conv 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. Furthermore, lip Am-B seems to be effective to prevent relapse of systemic mycosis in patients undergoing BMT.

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39th meeting of the American Society for Haemotology
    • ASH 39th (1998)