Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.

Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 106 CD34+ cells/kg for a single or ≥5 × 106 CD34+ cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34+ cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34+ cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 106 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19+ and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

The European LeukemiaNet: achievements and perspectives.

The only way to cure leukemia is by cooperative research. To optimize research, the European LeukemiaNet integrates 105 national leukemia trial groups and networks, 105 interdisciplinary partner groups and about 1,000 leukemia specialists from 175 institutions. They care for tens of thousands of leukemia patients in 33 countries across Europe. Their ultimate goal is to cure leukemia. Since its inception in 2002, the European LeukemiaNet has steadily expanded and has unified leukemia research across Europe. The European LeukemiaNet grew from two major roots: 1) the German Competence Network on Acute and Chronic Leukemias; and 2) the collaboration of European Investigators on Chronic Myeloid Leukemia. The European LeukemiaNet has improved leukemia research and management across Europe. Its concept has led to funding by the European Commission as a network of excellence. Other sources (European Science Foundation; European LeukemiaNet-Foundation) will take over when the support of the European Commission ends.

Role of the respiratory burst in co-operative reduction in neutrophil survival by influenza A virus and Escherichia coli.

Influenza A virus (IAV)-induced impairment of neutrophil function or survival may be a cause of bacterial superinfection of IAV-infected subjects. This study was performed to determine the mechanism through which the combination of IAV and Escherichia coli co-operatively reduces neutrophil survival. Neutrophil binding of annexin-V and caspase-3 activation was significantly increased by either IAV or E. coli, supporting the concept that the micro-organisms accelerate neutrophil apoptosis. The anti-apoptotic agent granulocyte-macrophage colony stimulating factor (GM-CSF) did not improve, but further reduced, survival of neutrophils treated with IAV and E. coli. As addition of E. coli resulted in greater neutrophil uptake of IAV and greater neutrophil respiratory burst responses to IAV, this study tested whether respiratory burst activation by IAV and E. coli contributes to reducing neutrophil survival. The cell-permeant NADPH oxidase inhibitor, diphenylene iodonium, significantly increased survival of neutrophils treated with either E. coli alone or the combination of IAV and E. coli. In contrast, catalase, which is not cell permeant, did not alter survival of E. coli- and IAV-treated neutrophils. Azide enhanced neutrophil hydrogen peroxide responses to IAV and E. coli, and reduced survival of these cells. These results indicate that co-operative induction of intracellular respiratory burst responses by IAV and E.coli mediates the reduced neutrophil survival caused by these pathogens in vitro.

Tetranectin Binds to the Kringle 1-4 Form of Angiostatin and Modifies Its Functional Activity.

Tetranectin is a plasminogen kringle 4 domain-binding protein present in plasma and various tissue locations. Decreased plasma tetranectin or increased tetranectin in stroma of cancers correlates with cancer progression and adverse prognosis. A possible mechanism through which tetranectin could influence cancer progression is by altering activities of plasminogen or the plasminogen fragment, angiostatin. Tetranectin was found to bind to the kringle 1-4 form of angiostatin (AST $;{\text{K1-4}}$ ). In addition, tetranectin inhibited binding of plasminogen or AST $;{\text{K1-4}}$ to extracellular matrix (ECM) deposited by endothelial cells. Finally, tetranectin partially counteracted the ability of AST $;{\text{K1-4}}$ to inhibit proliferation of endothelial cells. This latter effect of tetranectin was specific for AST $;{\text{K1-4}}$ since it did not counteract the antiproliferative activities of the kringle 1-3 form of angiostatin (AST $;{\text{K1-3}}$ ) or endostatin. These findings suggest that tetranectin may modulate angiogenesis through interactions with AST.

Management of infections in critically ill neutropenic cancer patients.

Because of improving antineoplastic treatment options with increasing cure rates, prolonging survival, and improving quality of life, the reluctance to admit patients with malignant disease to an intensive care unit is not justified; thus, the number of patients with malignancies treated in intensive care units rises. The use of more aggressive anticancer regimens leads to an increase of attendant infections, which are the most frequent and often life-threatening complications in cancer patients. A multidisciplinary practical approach to evaluation and treatment is needed to optimize treatment results and to meet the various diagnostic and therapeutic challenges in this subset of patients on an intensive care unit.