ANTIMYCOTIC THERAPY WITH LIPOSOMAL AMPHOTERICIN-B FOR PATIENTS UNDERGOING BONE-MARROW OR PERIPHERAL-BLOOD STEM-CELL TRANSPLANTATION

Suspected deep or systemic mycosis in patients undergoing high-dose th erapy and autologous or allogeneic bone marrow transplantation (BMT) r equires 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, B MT patients often receive other potential nephrotoxic drugs such as Cs A or virustatics. In this study, we report 74 BMT-patients treated wit h 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 wit h 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 wa s therapy stopped due to severe chills and fever. Severe organ impairm ent was not observed under therapy with liposomal amphotericin-B. Crea tinine decreased in five patients after an increase under preceding th erapy with the conventional formulation. Influence of liposomal amphot ericin-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, veno-occlusive disease (VOD), and graft-v ersus-host disease (GVHD). 10/11 culture positive patients died from a spergillosis (5/5) or candidiasis (5/6), but in 9/11 of these subjects the immunity was additionally compromised by GvHD, steroid therapy, a nd VOD. Liposomal amphotericin-B was effective in preventing relapse o f 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 o f liposomal amphotericin-B randomised against the conventional formula tion and that the comparison of patients undergoing BMT with patients under standard chemotherapy might be difficult because of additional r isk factors of the BMT-patients.