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To evaluate the efficacy and safety of voriconazole in acute invasive aspergillosis (IA), an open, noncomparative multicenter study was conducted. Immunocompromised patients with IA were treated with intravenously administered voriconazole 6 mg/kg twice a day (b.i.d.) twice and then 3 mg/kg b.i.d. for 6-27 days, followed by 200 mg b.i.d. administered orally for up to 24 weeks. Response was assessed by clinical and radiographic change. A total of 116 patients were assessable. IA was proven in 48 (41%) and probable in 68 patients. Voriconazole was given as primary therapy in 60 (52%). Good responses were seen in 56 (48%); 16 (14%) showed complete response and 40 (34%) partial response. A stable response was seen in 24 patients (21%), and 36 (31%) of the infections failed to respond to therapy. Good responses were seen in 60% of those with pulmonary or tracheobronchial IA (n = 84), 16% with cerebral IA (n = 19), 58% with hematologic disorders (n = 67), and 26% of allogeneic stem cell transplant recipients (n = 23). Voriconazole is efficacious in treating acute IA.

Background. Pulmonary mucormycosis (PM) is a life-threatening fungal infection with an increasing incidence among patients with acute leukemia. In some immunocompromised hosts, the reversed halo sign (RHS) has been described on the pulmonary computed tomographic (CT) scan of patients with mucormycosis. Methods. This study reports a single-center experience with PM exclusively in patients with acute leukemia. Clinical records, laboratory results, and CT scans were retrospectively analyzed to evaluate the clinical usefulness of the RHS for the early identification and treatment of PM, with regard to outcomes in these patients. Results. Between 2003 and 2012, 16 cases of proven PM were diagnosed among 752 consecutive patients receiving chemotherapy for acute myeloblastic or lymphoblastic leukemia. At the time PM was diagnosed, all patients but one were neutropenic. The study of sequential thoracic CT scans showed that during the first week of the disease, the RHS was observed in 15 of 16 patients (94%). Initially, other radiologic findings (multiple nodules and pleural effusion) were less frequent, but appeared later in the course of the disease (6% and 12% before vs 64% and 55% after the first week). After the diagnosis of PM, median overall survival was 25 weeks (range, 3–193 weeks), and 6 patients (38%) died before day 90. Conclusions. In the particular setting of neutropenic leukemia patients with pulmonary infection, the presence of the RHS on CT was a strong indicator of PM. It could allow the early initiation of appropriate therapy and thus improve the outcome.

Deletions of the 1p region appear as a pejorative prognostic factor in multiple myeloma patients (especially 1p22 and 1p32 deletions) but there is a lack of data on the real impact of 1p abnormalities on an important and homogeneous group of patients. To address this issue we studied by fluorescence in situ hybridization (FISH) the incidence and prognostic impact of 1p22 and 1p32 deletions in 1195 patients from the IFM (Institut Francophone du Myélome) cell collection. Chromosome 1p deletions were present in 23.3% of the patients (271): 15.1% (176) for 1p22 and 7.3% (85) for 1p32 regions. In univariate analyses, 1p22 and 1p32 appeared as negative prognostic factors for progression-free survival (PFS): 1p22: 19.8 months vs 33.6 months ( P <0.001) and 1p32: 14.4 months vs 33.6 months ( P <0.001); and overall survival (OS): 1p22: 44.2 months vs 96.8 months ( P =0.002) and 1p32: 26.7 months vs 96.8 months ( P <0.001). In multivariate analyses, 1p22 and 1p32 deletions still appear as independent negative prognostic factors for PFS and OS. In conclusion, our data show that 1p22 and 1p32 deletions are major negative prognostic factors for PFS and OS for patients with MM. We thus suggest that 1p32 deletion should be tested for all patients at diagnosis.

This investigation of the treatment of multiple myeloma compared one cycle of high-dose chemotherapy plus a single autologous stem-cell transplantation with two cycles of high-dose chemotherapy, each followed by stem-cell transplantation. The double-transplantation regimen had a substantial survival benefit. Survival benefits, especially for younger patients. The failure of conventional chemotherapy to improve the outlook in multiple myeloma 1 has led to the treatment of this disease with high-dose chemotherapy plus autologous stem-cell transplantation. Promising results have been obtained in pilot studies, 2 , 3 and randomized trials comparing autologous stem-cell transplantation with conventional chemotherapy in patients with newly diagnosed myeloma have been reported. 4 – 8 These studies demonstrated the superiority of autologous stem-cell transplantation over conventional treatment in terms of the response rate and event-free survival, but the effects on overall survival were unclear. A survival benefit was observed in French and British trials, 4 , 5 but not in others, . . .

In this trial, 700 patients with myeloma were randomly assigned to receive RVD therapy (lenalidomide, bortezomib, and dexamethasone) with or without autologous stem-cell transplantation. Patients who underwent transplantation had significantly longer progression-free survival. For the past 20 years, high-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. 1 – 3 However, this treatment requires hospitalization and can be associated with substantial toxic effects. Over the past decade, immunomodulatory drugs 4 – 14 and proteasome inhibitors 15 – 17 have been shown to have substantial activity in patients with multiple myeloma. The use of combination therapy with immunomodulatory drugs, proteasome inhibitors, and dexamethasone has yielded increased rates of complete response and improved outcomes, both among patients who are eligible for transplantation and among those who . . .

Lenalidomide maintenance after stem-cell transplantation significantly prolonged progression-free and event-free survival in patients with multiple myeloma. At 4 years, overall survival was similar in the lenalidomide-treated and placebo-treated groups. During the past decade, high-dose chemotherapy with autologous stem-cell transplantation has become the standard treatment for newly diagnosed myeloma in patients younger than 65 years of age. However, the median duration of response after this procedure does not exceed 3 years, and few patients remain free of the disease for more than 10 years. 1 – 4 Relapses are due to the failure of high-dose chemotherapy to eradicate all myeloma cells. Maintenance treatments have been proposed to control the proliferation of residual malignant cells after transplantation. For many years, interferon with or without glucocorticoids was used, 1 , 2 , 5 but this approach was . . .

The pharmacokinetics, efficacy, and safety of intravenous (iv) itraconazole (2 days at 400 mg/day, 12 days at 200 mg/day), followed by 12 weeks of oral capsules (400 mg/day) were studied in 31 immunocompromised patients with pulmonary invasive aspergillosis. All patients received iv itraconazole (median duration, 14 days), and 26 then received oral itraconazole (median duration, 78.5 days). After receiving iv itraconazole, concentrations increased rapidly, with trough plasma levels ⩾250 ng/mL in 91% of patients and in all patients by day 7. Concentrations ⩾500 ng/mL were observed in 64% of patients by day 2. Mean trough concentrations after 2 and 14 days were 670 and 850 ng/mL, respectively. Therapeutic levels were maintained after switching to oral capsules. A complete or partial response was seen at the last on-treatment assessment in 15 (48%) of 31 patients, with 6 (19%) showing stable disease. Itraconazole was well tolerated, with no unexpected effects. Overall iv/oral itraconazole was safe and effective in invasive aspergillosis.