Delayed introduction of G-CSF after chemotherapy does not affect peripheral blood stem cell yield and engraftment kinetics in children with high-risk malignancies: retrospective study of 45 cases

We retrospectively compared the effects of two time points of G-CSF (Filgrastim) introduction for PBSC mobilization in 45 children with different malignancies. Seventeen patients received the first G-CSF dose on day 2 or 3 following chemotherapy (group 1). Twenty-eight patients received a "flexible" G-CSF injection schedule when the G-GSF was started at the time of the first platelet count rise during post-chemotherapy recovery phase (group 2). Leukapheresis was performed when WBC recovery reached >2.0 x 10(9)/l or if the peripheral blood CD34(+) cell level was >0.01 x 10(9)/l. A median of 2 (1-4) leukapheresis procedures was performed in both groups to yield a median of 4.2 and 6.1 x 10(6) CD34(+) cells/kg in groups 1 and 2, respectively, which was generally sufficient for auto-transplantation. The proportion of patients with a failure of PBSC collection was similar and G-CSF consumption estimated through the total cycle dose was 2.3 times less in group 2 without increasing infectious risks. The short-term hematological recovery and the early post-transplant course were similar in the two groups. Delayed introduction of G-CSF after chemotherapy allowed PBSC harvest equivalent to that obtained after early G-CSF introduction. This approach could be an interesting alternative in PBSC mobilization but should be assessed by a prospective controlled study.     

New quantitative parameters on a recently introduced automated blood cell counter – the XE 2100TM

The XE 2100 (Sysmex Corporation) is a cell counter that furthers the technology of fluorescent flow cytometry developed from the earlier range of Sysmex analysers. The new diagnostic features are a nucleated red cell count (NRBC), the ability to measure platelets by impedance as well as an ‘optical’ platelet count using a fluorescence dye and an immature granulocyte (IG) count. The NRBC count was highly correlated (r=0.97) with the manual reference count. For counts below 100 × 10⁹/l the ‘optical’ method and the immunocount gave good a correlation (r=0.97) optical and impedance counts were also well correlated (r=0.89). The use of the ‘optical’ platelet count significantly improves the reliability of low platelet counts. The IG count correlated with visual counts (r=0.81) and allows the detection of immature cells at an earlier stage in the laboratory process. The introduction of fluorescent flow cytometric analysis allows extended quantification of additional cell populations and so potentially improves screening and monitoring of various pathological conditions.     

The lipocalin 24p3, which is an essential molecule in IL-3 withdrawal-induced apoptosis, is not involved in the G-CSF withdrawal-induced apoptosis

Many hematopoietic cells undergo apoptosis when deprived of specific cytokines. Lipocalin 24p3, reported to be induced in hematopoietic cells by interleukin 3 (IL-3) depletion, induces hematopoietic cell apoptosis despite the presence of IL-3. As granulocyte colony stimulating factor (G-CSF) depletion also induces the apoptosis of G-CSF-dependent cell line cells, we examined the effect of 24p3 on the apoptotic function induced by G-CSF depletion. 24p3 was induced by the depletion of IL-3, but not G-CSF, in cytokine-dependent cell lines. Although 24p3 suppressed growth induced by IL-3, it did not influence G-CSF-dependent cell growth. These observations show that 24p3 is not involved in the G-CSF withdrawal-induced apoptosis, although it is essential in IL-3 withdrawal-induced apoptosis.     

药物雾化吸入治疗小儿呼吸道感染的临床疗效及其对血清 C-反应蛋白、中性粒细胞、白细胞水平的影响

目的：探讨药物雾化吸入治疗小儿呼吸道感染的临床疗效及共对血清C-反应蛋白（ CRP）、中性粒细胞、白细胞水平的影响。方法将204例呼吸道感染患儿随机分为试验组和对照组各102例。试验组给予盐酸氨溴索雾化吸入治疗,对照组给予盐酸氨溴索静脉注射治疗。2组患者均给予相同对症治疗,抗生素抗感染和营养支持,检测2组患者治疗前后CRP、中性粒细胞及白细胞水平,观察2组患者治疗效果,比较其差异。结果治疗前2组CRP、中性粒细胞和白细胞差异均无统计学意义（P＞0．05）。治疗后2组CRP、中性粒细胞、白细胞水平均低于治疗前,且试验组低于对照组,差异均具有统计学意义（P＞0．05）。试验组患者咳嗽消失时间、啰音消失时间和住院时间均短于对照组,差异均有统计学意义（P＜0．05）。试验组患者治疗总有效率为91．18％远高于对照组的74．51％,差异有统计学意义（P＜0．05）。结论药物雾化吸入治疗小儿呼吸道感染可显著降低患者血清CRP、中性粒细胞、白细胞水平,缩短患者治疗所需时间,提高治疗效果。     

Impaired phagocyte respiratory burst responses to opportunistic fungal pathogens in transplant recipients: in vitro effect of r-metHuG-CSF (Filgrastim)

Abstract: Phagocyte respiratory burst capacity in response to pathogenic fungi and the in vitro effects of granulocyte colony-stimulating factor (G-CSF) were examined in 15 normal volunteers and 39 transplant recipients (4 autologous and 4 allogeneic bone marrow, 3 heart, 10 liver, 8 lung, and 10 kidney). Chemiluminescence was measured for reaction mixtures of diluted whole blood, opsonized fungi, and luminol, with and without in vitro incubation with r-metHuG-CSF (Filgrastim). Transplant patients exhibited significantly impaired respiratory burst responses to conidia and yeast compared with controls, but this was reversed with Filgrastim. Responses to hyphae were low for both groups, and G-CSF had little or no effect. There was excellent correlation between responses to fungi and responses to opsonized zymosan. In vitro respiratory burst capacity is impaired in transplant recipients. This may predict susceptibility to invasive fungal infections. G-CSF can reverse impaired phagocyte function and is of potential benefit in the prevention and/or treatment of fungal infection in transplant patients.     

Absence of mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene in patients with myelodysplastic syndrome/acute myeloblastic leukaemia occurring after treatment of aplastic anaemia with G-CSF

The development of myelodysplastic syndrome/acute myeloblastic leukaemia (MDS/AML) has been reported in patients with aplastic anaemia (AA) after administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Similarly, patients with severe congenital neutropenia (SCN) have an increased risk of developing MDS/AML after treatment with rhG-CSF. Point mutations in the G-CSF receptor gene are found in about 20% of SCN patients who are predisposed to MDS/AML. We investigated the occurrence of mutations in the G-CSF receptor in eight patients with AA who developed MDS/AML. No mutations were detected around the cytoplasmic domain of the gene in our patients, indicating that the mechanisms of clonal evolution to MDS/AML in patients with AA might be different from those with SCN.     

Use of granulocyte colony-stimulating factor (G-CSF) for mobilizing peripheral blood stem cells: risk of mobilizing clonal myeloma cells in patients with bone marrow infiltration

Peripheral blood stem cells have been used for autologous reconstitution of haemopoiesis after high dose cytotoxic therapy and produce similar disease response rates as autologous bone marrow transplants. Peripheral blood stem cell transplants are an especially attractive option for patients in whom marrow harvest is not feasible due to bone marrow damage or infiltration. Recombinant growth factors mobilize adequate numbers of stem cells from the marrow but their effect on tumour cell circulation kinetics is not known. We report a patient with multiple myeloma and bone marrow infiltration in whom the use of G-CSF for stem cell mobilization led to release of plasma cells into the peripheral circulation and contamination of the stem cell harvest.     

Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells

OBJECTIVES: We investigated whether a single episode of exercise could acutely increase the numbers of endothelial progenitor cells (EPCs) and cultured/circulating angiogenic cells (CACs) in human subjects. BACKGROUND: Endothelial progenitor cells and CACs can be isolated from peripheral blood and have been shown to participate in vascular repair and angiogenesis. We hypothesized that exercise may acutely increase either circulating EPCs or CACs. METHODS: Volunteer subjects (n = 22) underwent exhaustive dynamic exercise. Blood was drawn before and after exercise, and circulating EPC numbers as well as plasma levels of angiogenic growth factors were assessed. The CACs were obtained by culturing mononuclear cells and the secretion of multiple angiogenic growth factors by CACs was determined. RESULTS: Circulating EPCs (AC133+/VE-Cadherin+ cells) increased nearly four-fold in peripheral blood from 66 +/- 27 cells/ml to 236 +/- 34 cells/ml (p < 0.05). The number of isolated CACs increased 2.5-fold from 8,754 +/- 2,048 cells/ml of peripheral blood to 20,759 +/- 4,676 cells/ml (p < 0.005). Cultured angiogenic cells isolated before and after exercise showed similar secretion patterns of angiogenic growth factors. CONCLUSIONS: Our study demonstrates that exercise can acutely increase EPCs and CACs. Given the ability of these cell populations to promote angiogenesis and vascular regeneration, the exercise-induced cell mobilization may serve as a physiologic repair or compensation mechanism.