Moxifloxacin is more effective than tosufloxacin in reducing chemotherapy-induced febrile neutropenia in patients with hematological malignancies.

Recent studies have shown the prophylactic efficacy of fluoroquinolones against infections in patients with chemotherapy-induced neutropenia. However, little is known about the differences between fluoroquinolones, and there are some concerns about the emergence of resistant bacteria. In this retrospective study, we compared the prophylactic efficacy of moxifloxacin (MFLX) and tosufloxacin (TFLX) for chemotherapy-induced febrile neutropenia. The cumulative incidences of febrile neutropenia were 74.7% (59 of 79) in the MFLX group and 81.1% (219 of 270) in the TFLX group (log-rank test p = 0.044). Subgroup analysis revealed a more prominent prophylactic advantage of MFLX in patients with acute myeloid leukemia (AML) or long duration of neutropenia (p = 0.013 and 0.008, respectively). There were no significant differences in the incidences of adverse events and fluoroquinolone resistant bacteria in both groups. This study indicates that prophylaxis with MFLX is more beneficial to reduce febrile neutropenia episodes than TFLX, especially in patients with high-risk disease.

Gain-of-function mutations and copy number increases of Notch2 in diffuse large B-cell lymphoma.

Signaling through the Notch1 receptor has a pivotal role in early thymocyte development. Gain of Notch1 function results in the development of T-cell acute lymphoblastic leukemia in a number of mouse experimental models, and activating Notch1 mutations deregulate Notch1 signaling in the majority of human T-cell acute lymphoblastic leukemias. Notch2, another member of the Notch gene family, is preferentially expressed in mature B cells and is essential for marginal zone B-cell generation. Here, we report that 5 of 63 (approximately 8%) diffuse large B-cell lymphomas, a subtype of mature B-cell lymphomas, have Notch2 mutations. These mutations lead to partial or complete deletion of the proline-, glutamic acid-, serine- and threonine-rich (PEST) domain, or a single amino acid substitution at the C-terminus of Notch2 protein. Furthermore, high-density oligonucleotide microarray analysis revealed that some diffuse large B-cell lymphoma cases also have increased copies of the mutated Notch2 allele. In the Notch activation-sensitive luciferase reporter assay in vitro, mutant Notch2 receptors show increased activity compared with wild-type Notch2. These findings implicate Notch2 gain-of-function mutations in the pathogenesis of a subset of B-cell lymphomas, and suggest broader roles for Notch gene mutations in human cancers.