Summary.A retrospective study of 37 patients with haematological malignancy (21 acute myeloid leukaemia, 11 acute lymphoid leukaemia, two lymphoma, two hairy cell leukaemia, one Hodgkin's disease) and histologically documented mucormycosis was conducted to evaluate the clinical characteristics and ascertain the factors which influenced the outcome from mycotic infection. Patients were admitted to 18 haematology divisions in tertiary care or university hospitals in Italy between 1987 and 1995.Fever, thoracic pain, dyspnoea and cough were the most frequent presenting symptoms. At the onset, 89% patients were neutropenic (neutrophil counts < 0 . 5 × 10 9 /l) with a median duration of previous neutropenia of 14 d (range 6-60). The most frequent sites of infection were lungs (81%), CNS (27%), sinus (16%), liver (16%) and orbital space (10%). Only three patients were asymptomatic. A correct in vivo diagnosis was made in only 13 (35%) patients. When performed, thoracic and cranial CT scan were the most useful diagnostic investigations. Despite the fact that 26 febrile patients were treated with empirical antifungal treatment, 28 of the 37 patients (76%) died from fungal infection at a median time of 17 d from the onset of clinical symptoms. Nine patients were cured by antifungal therapy plus, in five cases, radical surgery procedures.An analysis of factors influencing outcome demonstrated that the resolution of chemotherapy-induced neutropenia and prolonged treatment with amphotericin B and, if feasible, radical surgical debridement treatment, were significantly correlated with recovery from infection. Mucormycosis, a rare filamentous fungal infection that occurs most frequently in neutropenic acute leukaemia patients, is characterized by a high mortality rate. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.

The prognostic value of 12 clinical and haematological parameters, recorded at diagnosis, in myelofibrosis with myeloid metaplasia (MMM) was retrospectively analysed in a consecutive series of 133 patients followed for a minimum of 60 months. Multivariate analysis showed that the following features were associated with a significantly shorter survival: (1) short period of time (less than 13 months) between first symptoms and diagnosis; (2) anaemia (haemoglobin less than 10 g/dl); (3) leucocyte count greater than 12 x 10(9)/l; (4) peripheral blood granulocyte precursors greater than 10%. Age, splenectomy and percentage of peripheral blood metamyelocytes were found significantly to affect survival only from univariate analysis, whereas sex, size of spleen, thrombocytopenia and thrombocytosis were of no prognostic significance. These data suggest that a more intensive chemotherapy might be useful for younger patients with bad prognostic factors at diagnosis.

One hundred and twenty-six patients were treated for 137 episodes of fungal infection with liposomal amphotericin B (AmBisome) at 43 investigational centres. Among the patients were 72 with malignancies, 17 organ transplant recipients, 20 patients with immunological disorders and 17 others. AmBisome treatment was instituted after toxicity from previous amphotericin B treatment in 49 cases, nephrotoxicity or renal insufficiency in 40 and failure of previous antifungal treatment in 41. One hundred and eight episodes were clinically evaluable; among these 52 were caused by Candida spp. and 34 by Aspergillus spp. Ninety-nine patients were treated for at least eight days with a maximum dose of 0.7-5 mg/kg/day. Among 64 cases with proven invasive fungal infection 58% were cured. Fungi were eradicated in 35 of 54 (65%) mycologically evaluable cases. The cumulative dose was 3.2 +/- 3.2 (mean +/- S.D.) in cases where fungi were eradicated in comparison with 3.3 +/- 2.3 g in cases where fungi persisted. The eradication rate was 83% for Candida spp. compared with 41% for Aspergillus spp. (P less than 0.01). Among 24 cases with presumptive invasive fungal infections 14 (58%) were cured. Candida spp. were eradicated in seven of ten of these cases. Among 11 cases with superficial fungal infections eight were cured and three improved. Candida spp. were eradicated in four of five patients. It is concluded that AmBisome is an effective antifungal agent in a majority of patients with invasive or superficial fungal infections.

Common anionic nucleophiles such as those derived from inorganic salts have not been used for enantioselective catalysis because of their insolubility. Here, we report that merging hydrogen bonding and phase-transfer catalysis provides an effective mode of activation for nucleophiles that are insoluble in organic solvents. This catalytic manifold relies on hydrogen bonding complexation to render nucleophiles soluble and reactive, while simultaneously inducing asymmetry in the ensuing transformation. We demonstrate the concept using a chiral bis-urea catalyst to form a tridentate hydrogen bonding complex with fluoride from its cesium salt, thereby enabling highly efficient enantioselective ring opening of episulfonium ion. This fluorination method is synthetically valuable considering the scarcity of alternative protocols and points the way to wider application of the catalytic approach with diverse anionic nucleophiles.