Summary:Liposomal amphotericin (AmBisome) 2 mg/kg three times weekly was compared with placebo as prophylaxis against fungal infection in patients undergoing chemotherapy or bone marrow transplantation (BMT) for haematological malignancies. Prophylaxis began on day 1 of chemotherapy and continued until neutrophils regenerated or infection was suspected. Of 161 evaluable patients, 74 received AmBisome and 87 received placebo. Proven fungal infections developed in no patients on AmBisome and in three on placebo (3.4%) (P ؍ NS). Suspected fungal infections requiring intervention with systemic antifungal therapy (usually amphotericin B) occurred in 31 patients on AmBisome (42%) and in 40 on placebo (46%) (P ؍ NS). Suspected deep-seated infections developed in 21 (28.3%) and 31 (35.6%) patients, respectively (P ؍ NS). Time to develop a suspected or proven deep-seated infection showed a trend in favour of AmBisome (P ؍ 0.11). Fifty patients had fungal colonisation (48 with Candida spp, two with Aspergillus spp) of at least one body site during prophylaxis; 15 patients while receiving AmBisome (20%) and 35 while on placebo (40%) (P Ͻ 0.01). Time to colonisation was significantly delayed in the group receiving AmBisome (P Ͻ 0.05). Treatment-related toxicity was modest and no additional toxicity was observed in patients receiving AmBisome. AmBisome 2 mg/kg three times weekly is safe and reduces fungal colonisation in patients receiving intensive chemotherapy or BMT. However, despite encouraging trends, prophylactic AmBisome did not lead to a significant reduction in fungal infection or in requirement for systemic antifungal therapy. Keywords: AmBisome; prophylaxis; neutropenia More than half the fatal infections in neutropenic patients are due to fungi 1 with candida and aspergillus the most commonly-observed pathogens. fungal infection increases with the severity and duration of neutropenia which, in the case of bone marrow transplantation (BMT) or chemotherapy for the treatment of haematological malignancies, can range from a few days to several weeks. The severe immunosuppression induced by high-dose corticosteroids given to recipients of allogeneic BMT to suppress graft-versus-host disease (GVHD) puts them at additional risk of fungal infections 2-4 whereas for patients receiving autologous stem cell support and treatment with growth factors the risk is much lower.5 This provides a rationale for the prophylactic use of antifungal agents.Orally administered agents such as the imidazoles, or non-absorbable amphotericin B, achieve only local decontamination and have little or no impact on invasive fungal infections. 6 A recent meta-analysis 7 has been conducted of 24 trials in which antifungals were used, either as prophylaxis or as empirical therapy, in patients with cancer complicated by neutropenia. This meta-analysis showed that amphotericin B decreased mortality significantly although the studies were small, as was the difference in the number of deaths. Antifungals as a group decreased the incidence of inv...
Summary. Peripheral blood stem cell (PBSC) mobilization using idarubicin and cytarabine was investigated in 40 patients with chronic myeloid leukaemia in first chronic phase (CML CP1). Disease contamination was evaluated in harvests from 41/44 (93%) mobilization episodes. Using cytogenetics, 22/37 (59%) showed a complete or major response; Southern blot analysis demonstrated a complete or major response in 9/17 (53%). No harvests were RT-PCR negative. In the 41 evaluable episodes, more complete or major responses were seen when PBSC mobilization occurred within 24 months [17/23 (74%) versus 6/18 (33%); P ¼ 0 : 02] and within 12 months of diagnosis [10/11 (91%) versus 13/30 (43%); P ¼ 0 : 018]. 20 patients underwent PBSC transplantation and 18/20 successfully engrafted. Post-transplant cytogenetic analysis was available on 15 cases, of whom five achieved a major cytogenetic response at 1-3 months, with five partial cytogenetic remissions. Two of 40 patients died during mobilization therapy (5%) and three of 20 after the transplant (15%). Overall mortality was high at five of 40 patients, and the procedural mortality was 20%. This study demonstrates that Ph-negative PBSCs can be mobilized in a significant proportion of patients with CML CP1, with the best results observed within a year of diagnosis. These cells can subsequently be used for autologous transplantation, however, the impact on long-term survival requires longer follow-up, and potential benefits may be compromised by the high mortality.
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