Distribution of BCL2 breakpoints in follicular lymphoma and correlation with clinical features: specific subtypes or same disease?

The t(14;18)(q32;q21) translocation is closely associated with follicular lymphoma (FL), and is routinely assessed with molecular methods exploring BCL2 breakpoints for both diagnosis and minimal residual disease (MRD) monitoring. We and others have previously reported new recurrent breakpoints (3'BCL2 and 5'mcr) which could be easily analyzed. In this study, we characterized the BCL2 breakpoints in 113 untreated patients with t(14;18)-positive FL and correlated their location with the location of JH break and with the clinical features. Breakpoints were respectively located at the major breakpoint region (MBR) in 73 cases (65%), at the minor cluster region (mcr) in 10 cases (9%), at 3'BCL2 in 14 cases (12%) and at 5'mcr in seven cases (6%). Finally, the breakpoint could not be located in nine patients (8%). 5'mcr cases were associated with bulky and high-stage disease, with frequent extranodal involvement and bone marrow infiltration. Survival studies did not show any correlation between breakpoint location and clinical outcome. The joining JH6 segment was the most frequently involved whatever the breakpoint location. In conclusion, unusual BCL2 breakpoints are found in about 20% of newly diagnosed follicular lymphomas and their study should be considered in the investigation of BCL2-JH rearrangement. It was not possible, in this series, to demonstrate any correlation between breakpoint location and either initial characteristics of the disease or survival of the patients.

Itraconazole oral solution for primary prophylaxis of fungal infections in patients with hematological malignancy and profound neutropenia: a randomized, double-blind, double-placebo, multicenter trial comparing itraconazole and amphotericin B.

Systemic and superficial fungal infections are a major problem among immunocompromised patients with hematological malignancy. A double-blind, double-placebo, randomized, multicenter trial was performed to compare the efficacy and safety of itraconazole oral solution (2.5 mg/kg of body weight twice a day) with amphotericin B capsules (500 mg orally four times a day) for prophylaxis of systemic and superficial fungal infection. Prophylactic treatment was initiated on the first day of chemotherapy and was continued until the end of the neutropenic period (>0.5 x 10(9) neutrophils/liter) or up to a maximum of 3 days following the end of neutropenia, unless a systemic fungal infection was documented or suspected. The maximum treatment duration was 56 days. In the intent-to-treat population, invasive aspergillosis was noted in 5 (1.8%) of the 281 patients assigned to itraconazole oral solution and in 9 (3.3%) of the 276 patients assigned to oral amphotericin B; of these, 1 and 4 patients died, respectively. Proven systemic fungal infection (including invasive aspergillosis) occurred in 8 patients (2.8%) who received itraconazole, compared with 13 (4.7%) who received oral amphotericin B. Itraconazole significantly reduced the incidence of superficial fungal infections as compared to oral amphotericin B (2 [1%] versus 13 [5%]; P = 0.004). Although the incidences of suspected fungal infection (including fever of unknown origin) were not different between the groups, fewer patients were administered intravenous systemic antifungals (mainly intravenous amphotericin B) in the group receiving itraconazole than in the group receiving oral amphotericin B (114 [41%] versus 132 [48%]; P = 0.066). Adequate plasma itraconazole levels were achieved in about 80% of the patients from 1 week after the start of treatment. In both groups, the trial medication was safe and well tolerated. Prophylactic administration of itraconazole oral solution significantly reduces superficial fungal infection in patients with hematological malignancies and neutropenia. The incidence of proven systemic fungal infections, the number of deaths due to deep fungal infections, and the use of systemic antifungals tended to be lower in the itraconazole-treated group than in the amphotericin B-treated group, without statistical significance. Itraconazole oral solution is a broad-spectrum systemic antifungal agent with prophylactic activity in neutropenic patients, especially for those at high risk of prolonged neutropenia.