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Summary:Cardiotoxicity has rarely been reported as a complication of melphalan or fludarabine administration as single agents. Recently, melphalan and fludarabine have been used in combination as non-myeloablative conditioning chemotherapy prior to allogeneic stem cell transplantation. We have observed the development of severe left ventricular failure in three of 21 patients treated with this combination. Cardiotoxicity in this context has not previously been reported and has implications for the assessment, monitoring and treatment of patients undergoing pre-transplant conditioning with melphalan and fludarabine. Bone Marrow Transplantation (2001) 28, 101-103. Keywords: emlphalan; fludarabine; BMT; cardiotoxity The alkylating agent melphalan, either alone or in combination with other agents such as busulphan and total body irradiation, has been widely used in myeloablative conditioning regimens prior to stem cell transplantation for diseases such as multiple myeloma, 1 non-Hodgkin lymphoma 2 and Hodgkin's disease. 3 The clinical utility of melphalan has recently been extended by the development of nonmyeloablative transplant regimens intended to exploit the graft-versus-tumour effect of allogeneic T cell chimerism whilst reducing the toxicities associated with myeloablative conditioning. 4 Non-myeloablative regimens have seen melphalan used in novel combinations with agents such as the purine analogue, fludarabine. 5 The application of these novel regimens is particularly attractive in patients considered too old for standard allografts.It is conceivable that these regimens may lead to unexpected toxicities due to the cumulative or synergistic effects of the individual drugs, particularly in an older patient population. Although cardiac dysfunction is well described with other alkylating agents such as cyclophosphamide, 6 single-agent melphalan has not been shown to affect cardiac contractility in prospective studies. also only been rarely associated with cardiac dysfunction, with a single report of non-fatal congestive heart failure in two of 27 patients treated for chronic lymphocytic leukaemia. 8 Conditioning regimens combining fludarabine and melphalan have been associated with veno-occlusive disease and mucosal toxicity, but development of cardiotoxicity had not been specifically assessed in earlier reports. 5,9 Recently, in an updated series, reduced-intensity conditioning with melphalan and purine analogues was associated with the development of Bearman grade 3-4 cardiotoxicity in four of 86 patients. 10 The clinical features of cardiotoxicity in this setting have not, however, been documented. We describe the development of severe left ventricular failure (LVF) in three of 21 patients undergoing non-myeloablative stem cell transplantation (NMSCT) following conditioning with these agents. Case reportsTwenty-one patients have undergone NMSCT following conditioning with melphalan and fludarabine at our institution for multiple myeloma (11), chronic lymphocytic leukaemia (3), chronic myeloid leukaemia (2),...

Treatment of invasive fungal infections is increasingly complex. Amphotericin B deoxycholate has long been the mainstay of treatment. However, there has been increasing recognition of both the propensity for nephro-toxicity in haematology, transplant and intensive care patients as well as its adverse impact on morbidity and mortality. This has coincided with the availabilty of newer, and in certain settings, more effective antifungal agents. Although the newer agents clearly cause less nephrotoxicity than amphotericin B, drug interactions, hepatic effects and unique side-effects need to be considered. The spectrum of the newer triazoles and echinocandins varies, highlighting the importance of accurate identification of the causative organism where possible. Consensus Australian guidelines have been developed to assist clinicians with treatment choices by reviewing the current evidence for the efficacy, the toxicity and the cost of these agents.

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Evidence-based guidelines for the treatment of established fungal infections in the adult haematology/oncology setting were developed by a national consensus working group representing clinicians, pharmacists and microbiologists. These updated guidelines replace the previous guidelines published in the Internal Medicine Journal by Slavin et al. in 2004. The guidelines are pathogen-specific and cover the treatment of the most common fungal infections including candidiasis, aspergillosis, cryptococcosis, zygomycosis, fusariosis, scedosporiosis, and dermatophytosis. Recommendations are provided for management of refractory disease or salvage therapies, and special sites of infections such as the cerebral nervous system and the eye. Because of the widespread use newer broad-spectrum triazoles in prophylaxis and empiric therapy, these guidelines should be implemented in concert with the updated prophylaxis and empiric therapy guidelines published by this group. This section of the guidelines is dedicated to the management of established invasive antifungal infections (IFI) in the adult haematology/oncology setting. Our recommendations are based on the antifungal agents licensed for use in Australia at the time of writing, and are organized according to pathogen.Where there is a radiological abnormality on computed tomography (CT)/high resolution computed tomography (HRCT) without early microbiological confirmation, clinicians should consider the most common clinical scenario. Microbiological confirmation with histology and/or culture should be pursued in all cases where the patient's clinical status permits additional investigations, such as bronchoscopy and/or biopsy. Newer diagnostic modalities such as polymerase chain reaction (PCR), galactomannan (GM) testing and molecular sequencing, are becoming increasingly available, particularly at specialist centres, and will play an increasing role in identifying probable and proven fungal infections. They are discussed in detail in the previous section of the guidelines by Morrissey et al.When considering the possibility of mould infections, Aspergillus is still the most likely organism within the Australasian setting.