Clinical implications, safety, efficacy of Recombinant Human Granulocyte Colony-Stimulating Factors and Pegylated Equivalent

A wide use of recombinant human granulocyte colony-stimulating factors (G-CSFs) and their pegylated equivalent is a significant step forward in the treatment of both solid tumors and hematological malignancies. Evidence-based use of these molecules resulted in more intensive treatments, safely extended to frail and elderly patients, and development of response- and comorbidity-tailored approaches. The available G-CSFs are filgrastim, and the long-acting PegFilgrastim, which are produced in E. Coli cells, and are chemically different from native human G-CSF, and lenograstim, a molecule produced in mammalian cells, with a chemical structure identical to native human G-CSF. These chemical differences produce a diverse interaction with receptors and stimulated neutrophils. For instance, lenograstim binds to receptors in the same way of endogenous ligand, and neutrophils obtained from stimulation with this G-CSF have a physiological activity profile similar to neutrophils normally generated in humans. Conversely, the different interaction between filgrastim and G-CSF receptor is more frequently associated with morphological abnormalities, reduced motility and chemotaxis and a reduced response to bacterial stimuli in induced neutrophils. On this background, we reviewed available evidence in order to analyze the impact of these chemical and pharmacodynamic differences among G-CSF molecules on safety, particularly in healthy peripheral-blood stem-cells donors, functional qualities of inducted neutrophils, and mobilization of hematopoietic stem cells.&nbsp

Primary cardiac lymphoma with isolated parenchymal central nervous system relapse: Report of two cases and review of the literature

Primary cardiac lymphoma (PCL) is a rare subset of non-Hodgkin's lymphoma involving the heart and/or pericardium with no or minimal evidence of extracardiac involvement at presentation. Distant relapses have infrequently been observed. We report two cases of this disorder that showed isolated central nervous system (CNS) relapse. Diagnosis by endomyocardial biopsy was consistent with diffuse large B-cell lymphoma. After immunochemotherapy they achieved complete remission (CR). Eight and five weeks after, isolated CNS relapses were observed respectively. The first patient was treated with high-dose methotrexate (HD-MTX) and high-dose cytarabine, resulting in a second CR. She then went onto receive autologous stem-cell transplantation but unfortunately died shortly after because of infection. The second patient received systemic CNS prophylaxis with HD-MTX, and later she was treated with an induction chemotherapy strategy with evidencing of progressive disease after two courses of treatment. She was subsequently initiated on a salvage therapy with cytarabine, followed by whole-brain radiotherapy, and autologous stem-cell transplant (ASCT), finally achieving a complete remission. Isolated CNS relapse is a very uncommon pattern in PCL and a standard approach to treatment is not yet well established. Nevertheless, the importance of CNS evaluation, using magnetic resonance imaging (MRI) and lumbar puncture, in patients with PCL should be considered, and further studies are recommended to determine the appropriate management of this complication