There is increasing evidence that stem cell (SC) mobilization to the heart and their differentiation into cardiac cells is a naturally occurring process. We sought to assess the safety and feasibility of granulocyte-colony stimulating factor (G-CSF) administration in humans to enhance SC mobilization and left ventricle (LV) injury repair during myocardial infarction (MI).

Antimicrobial solutions are widely used in the nursing care of chemotherapy induced oral mucositis (OM). There is little evidence, however, supporting their use for reducing mucosal damage. In our study, 132 patients were randomized to use normal saline (n=65) or povidone-iodine diluted 1:100 (n=67) mouthwashes for OM prophylaxis and treatment after high-dose chemotherapy comprising BEAM or HD-L-PAM followed by autologous peripheral stem cell transplantation. The study groups were well balanced in respect of age, sex, chemotherapy and the number of CD34+ cells in the graft. No significant difference was found between the groups in respect of OM characteristics, fever of unknown origin (FUO) and other infections. The antimicrobial solution was less tolerable for patients. OM occurred significantly more often in females than in males (86% vs 60%, P=0.0016) and was worse and of longer duration. The mechanical effect of mouthwashes might have a certain importance in FUO prevention. When indicating oral rinses, the patient's individual preference and tolerance of solutions offered should be considered.

The prognosis for women with primary breast cancer involving multiple axillary nodes remains poor. High-dose chemotherapy with stem-cell support produced promising results in initial clinical trials conducted at single institutions.

The number of circulating endothelial progenitor cells (EPCs) correlates with endothelial dysfunction and cardiovascular risk in humans. We explored whether angiotensin II receptor antagonist therapy affects the number of regenerative EPCs in patients with type 2 diabetes. In a prospective double-blind parallel group study, we randomly treated 18 type 2 diabetics with olmesartan (40 mg) or placebo for 12 weeks. We analyzed circulating CD34+ hematopoietic progenitor cells (flow cytometry) and EPCs (in vitro assay) before and after therapy. We verified the results in a second open trial treating 20 type 2 diabetics with 300 mg of irbesartan for 12 weeks. The number of EPCs was significantly lower in diabetic patients as compared with 38 age-matched healthy subjects (210+/-10 versus 258+/-18 per high-power field; P<0.05), whereas there was no significant difference with respect to hematopoietic progenitor cells. Treatment with olmesartan (n=9) significantly increased EPCs from 231+/-24 to 465+/-71 per high-power field (P<0.05), but not hematopoietic progenitor cells. In contrast, placebo treatment (n=9) did not affect EPCs and hematopoietic progenitor cells. With irbesartan therapy, EPC number increased significantly from 196+/-15 to 300+/-23 per high-power field (P<0.05) already after 4 weeks of treatment. At the end of 12-week therapy, patients had 310+/-23 EPCs per high-power field (P<0.05 versus baseline). Angiotensin II receptor antagonists increase the number of regenerative EPCs in patients with type 2 diabetes mellitus. This action may be of therapeutic relevance contributing to their beneficial cardiovascular effects.

Patients undergoing autologous hematopoietic stem cell transplantation (autoHCT) are at increased risk for infection with Streptococcus pneumoniae and have impaired antibody responses to pneumococcal polysaccharide vaccines. We performed this study to examine the ability of autoHCT patients to respond to a heptavalent pneumococcal conjugate vaccine (PCV7) given after transplantation and to determine whether there was a potential benefit of immunizing these patients before stem cell collection. Sixty-one patients scheduled for autoHCT were randomized to receive either PCV7 or no vaccine before stem cell collection. After stem cell reinfusion, all study patients were immunized with PCV7 at 3, 6, and 12 months. Pneumococcal immunoglobulin G antibody concentrations were measured at the time of each immunization and 1 month after the 12-month dose. Serotype-specific pneumococcal antibody concentrations were significantly higher in patients immunized with PCV7 before stem cell collection compared with patients not immunized before their stem cells were collected for 6 of 7 serotypes at 3 months, 6 of 7 serotypes at 6 months, 4 of 7 serotypes at 12 months, and 3 of 7 serotypes at 13 months. After the 3-dose series of PCV7 after autoHCT, >60% of study patients had protective concentrations of antibody to all 7 vaccine serotypes regardless of immunization before stem cell collection. Pneumococcal conjugate vaccine is immunogenic in autoHCT patients and may be an effective strategy to prevent invasive disease after transplantation.

This study was performed to investigate the effects of a relaxation breathing exercise on anxiety, depression, and leukocyte count in patients who underwent allogenic hemopoietic stem cell transplantation. Thirty-five patients were randomly selected, with 18 assigned to an exercise group and 17 assigned to a control group. The exercise intervention was applied to the exercise group for 30 minutes every day for 6 weeks. It consisted of physical exercises combined with relaxation breathing. Anxiety was measured by the State-Trait Anxiety Inventory and depression was measured by the Beck Depression Inventory. The total number of leukocytes was calculated from total and differential counts of peripheral white blood cells. The exercise group had a greater decrease in anxiety and depression than did the control group, but the total number of leukocytes did not significantly differ between the two groups. These findings indicate that a relaxation breathing exercise would improve anxiety and depression levels in patients who undergo allogenic hemopoietic stem cell transplantation, but would not affect the number of leukocytes.

Minimal residual disease (MRD) present in peripheral blood stem cell (PBSC) products of AML patients may contribute to relapse. Our goal was to 1) predict leukemia recurrence based on the frequency of MRD present in PBSC products, 2) establish the efficacy of different purging procedures, and 3) integrate this into a model that enables to predict whether or not to purge.

Eosinophils develop from CD34+ haematopoietic progenitor cells. Allergen exposure in susceptible individuals is known to induce a local eosinophilic inflammation, but the effect on progenitor cells is much less understood.

Bone marrow (BM) and blood stem cell (BSC) allografts differ considerably with respect to their content of progenitor cells and progenitor cell subsets as well as mature lymphocytes. The aim of this prospective, randomized study was to determine whether these differences have an impact on early post-transplant immune recovery.

Dietary n-3 polyunsaturated fatty acids (PUFA) may represent a mode of allergy prevention. Cord blood (CB) CD34+ hemopoietic progenitors are altered in infants at risk of atopy. We therefore studied the effects of dietary n-3 PUFA supplementation during pregnancy on numbers and function of progenitors in neonates at high risk of atopy. In a double-blind study, atopic, pregnant women were randomized to receive fish oil capsules or placebo from 20 wk gestation until delivery. At birth, CB CD34+ cells were isolated and analyzed by flow cytometry for expression of cytokine (IL-5Ralpha, IL-3Ralpha, granulocyte/macrophage colony-stimulating factor Ralpha) or chemokine (CXCR4 and CCR3) receptors. CB cells were also cultured in methylcellulose assays for eosinophil/basophil colony-forming cells. At age 1 y, infants were clinically assessed for atopic symptoms and skin tests. Percentages of CB CD34+ cell numbers were higher after n-3 PUFA than placebo. Co-expression of cytokine or chemokine receptors on CD34 cells was not altered by n-3 PUFA supplementation. However, there were significantly more IL-5-responsive CB eosinophil/basophil colony forming units (Eo/B-CFU) in the fish oil, compared with the control, group. Overall, there was a positive association between CD34+ cells and IL-5-responsive Eo/B-CFU in CB and 1 y clinical outcomes, including atopic dermatitis and wheeze. Dietary n-3 PUFA supplementation during pregnancy in atopic mothers alters infant cord blood hemopoietic progenitor phenotype. This may have an impact on development of atopic disease.

The ability of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration to increase the content of blood leucocytes and hematopoietic progenitor cells (HPCs) is well established, yet the effect of these cytokines on immune function is less well described. Recent data indicate that plasmacytoid dendritic cells (DC2) may inhibit cellular immune response. We hypothesized that administration of the combination of G-CSF and GM-CSF after chemotherapy would reduce the type 2, or plasmacytoid, DC2 content of the autologous blood HPC grafts compared with treatment with G-CSF alone. To test this hypothesis, 35 patients with lymphoma and myeloma were randomized to receive either G-CSF or the combination of G-CSF plus GM-CSF after chemotherapy, and blood HPC grafts were collected by apheresis. Cytokine-related adverse events between the 2 groups were similar. More than 2 x 10(6)CD34 + cells per kilogram were collected by apheresis in 14 of 18 subjects treated with G-CSF and in 16 of 17 subjects treated with GM-CSF plus G-CSF ( p = not significant). There were minor differences between the 2 groups with respect to the content of T cells and CD34 + cells in the apheresis products. However, grafts collected from recipients of the combination of GM-CSF plus G-CSF had significantly fewer DC2 cells and similar numbers of DC1 cells compared with recipients treated with G-CSF alone. A third cohort of patients received chemotherapy followed by the sequential administration of G-CSF and the addition of GM-CSF 6 days later. Grafts from these patients had a markedly reduced DC2 content compared with those from patients treated either with G-CSF alone or with the concomitant administration of both cytokines. These data, and recent data that cross-presentation of antigen by DC2 cells may induce antigen-specific tolerance among T cells, suggest that GM-CSF during mobilization of blood HPC grafts may be a clinically applicable strategy to enhance innate and acquired immunity after autologous and allogeneic HPC transplantation.

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma.

This prospective and randomized study was conducted to evaluate clinical and economic consequences of using granulocyte colony-stimulating factor (G-CSF) following autologous peripheral blood progenitor cell (PBPC) transplantation in children. Between January 1999 and December 2003, 117 patients underwent autologous PBPCT: 51 patients received G-CSF following PBPCT, while 66 patients did not receive G-CSF. Median time to absolute neutrophil count > 0.5 x 10(9)/l was 10 days in the treatment group and 11 days in the control group (P < 0.009). The median time to platelets >20 x 10(9)/l was 12 days in both groups (P = NS). The median time to platelets >50 x 10(9)/l was 15 days in the G-CSF group and 14 days in the control group (P<0.005). In patients who received <5 x 10(6)/kg CD34+ cells, the median time to platelets >20 x 10(9)/l and >50 x 10(9)/l was similar with or without G-CSF (12 and 15 days, respectively). Platelet transfusion requirements were lower in the control group (2 vs 3 U in G-CSF group). There was a trend towards higher total costs with G-CSF: 8146.82 Euros and 7873.34 Euros with and without G-CSF, respectively (P = 0.1). Our data suggest that there is no indication of the standard application of G-CSF in children following PBPC transplantation. The only possible indication is the group of patients with a lower yield of CD34+ cells.

The infarct size determines the long-term prognosis of patients with acute myocardial infarction (AMI). There is a growing interest in repairing scar area by transplanting bone marrow stem cells. However, effectiveness of intracoronary injection of bone marrow mesenchymal stem cells (BMSCs) in patients with AMI still remains unclear.

The Transplantation of Progenitor Cells And Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) trial investigates both safety, feasibility, and potential effects on parameters of myocardial function of intracoronary infusion of either circulating progenitor cells (CPC) or bone marrow-derived progenitor cells (BMC) in patients with acute myocardial infarction (AMI).

To observe the combined effect of etoposide (Vp-16) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) on mobilization of autologous peripheral blood stem cells (APBSC) in malignant tumor patients and find out the suitable dose of Vp-16.

We designed a prospective, randomized clinical trial to evaluate the immune response to thymic and peripheral infusions of donor haematopoietic stem cells (HSCs) to create tolerance in recipients of cadaver renal allografts.

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.

Breast cancer patients with four or more positive axillary lymph nodes who are treated with conventional adjuvant therapy have a poor prognosis. In uncontrolled studies, high-dose chemotherapy produced much better results than conventional therapy. We compared the benefits of a single cycle of high-dose chemotherapy and the benefits of conventional chemotherapy in patients with high-risk breast cancer in a prospective, unblinded, randomized trial.

Nitric oxide synthase (NOS) inhibitors are considered promising as a therapeutic option in severe septic shock. The aim of this study was to investigate the effects of N-nitro-L-arginine methyl ester (L-NAME) application on neutrophil (PMN) respiratory burst, phagocytosis, and elimination of Escherichia coli from blood and tissue in rabbits. Twenty-eight female chinchilla rabbits were randomized to a treatment and control group. To quantify the bacterial clearance process, 10 colony forming units (CFU) of E. coli were injected intravenously into anesthetized rabbits. Animals in the L-NAME group had a significantly higher mortality compared with controls. NOS inhibition resulted in a significant delay of bacterial clearance (P < 0.001). These findings correlated with a significant augmentation of all organ E. coli findings (P = 0.002-0.035). PMN phagocytosis activity was notably reduced by L-NAME treatment during the experimental observation. Neutrophil burst, on the other hand, was amplified by NOS inhibition (P = 0.008). Our findings point to an interference with the PMN-dependent immune mechanisms after L-NAME treatment. The augmented PMN burst reaction could be a compensatory mechanism, potentially leading to tissue damage. Therefore, in this model, we find sufficient evidence pointing to a possible cause for the deleterious effect of early nonselective NOS inhibition in critically ill patients.