Upfront allogeneic blood stem cell transplantation for patients with high-risk myelodysplastic syndrome or secondary acute myeloid leukemia using a FLAMSA-based high-dose sequential conditioning regimen.

Patients suffering from high-risk myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) secondary to MDS (sAML) are characterized by poor response to conventional cytotoxic chemotherapy. The purpose of our prospective single-center study was to examine the safety and efficacy of an allogeneic hematopoietic stem cell transplantation (HSCT) following a sequential conditioning regimen as first-line therapy for previously untreated patients with high-risk MDS or sAML. Between November 2003 and June 2010, 30 patients (20 high-risk MDS, 10 sAML) received fludarabine (4 × 30 mg/m(2)), amsacrine (4 × 100 mg/m(2)), and Ara-C (4 × 2 g/m(2), FLAMSA). After 2 to 3 days of rest, patients received high-dose melphalan alone (200 mg/m(2) for patients with an age <50 years, 150 mg/m(2) for patients with an age between 50 and 60 years, and 100 mg/m(2) for patients with an age >60 years; n = 24) or melphalan and thiotepa (10 mg/kg, Mel/Thio, n = 6). Following these high-dose conditioning regimens, a median number of 7.7 × 10(6) CD34(+) cells/kg body weight (range: 2.9 × 10(6)-17.2 × 10(6)) were transplanted from 13 related or 17 unrelated donors. Antithymocyte globulin (Fresenius 30-60 mg/kg) as well as tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. All patients except 1 with primary graft failure achieved complete remission after HSCT. After a median follow-up time of 28 months (range: 7-81), 21 patients (70%) were alive and free of disease. Overall, 4 patients relapsed. At 2 years, overall survival, event-free survival, and treatment-related mortality were 70%, 63%, and 30%, respectively. Because of undue toxicity, thiotepa is no longer part of the conditioning regimen. Our results add to the body of evidence that a FLAMSA-based sequential conditioning therapy is effective for previously untreated patients with high-risk MDS or sAML.

Electrochemical Studies of Stainless Steel and Stainless Steel-TiO2 Composite in Reference to Molten Aluminum Alloy Using a Solid-State BaCO3 Electrolyte.

The influence of TiO2 addition on the high-temperature electrochemical characteristics of stainless-steel-based materials was investigated by means of differential potential measurement, electrochemical polarization and impedance spectroscopy. A new three-electrode approach was utilized which incorporated a liquid aluminum alloy AlSi7Mg0.3 as the reference electrode, barium carbonate BaCO3 as the solid-state electrolyte, and stainless steel or a stainless steel-TiO2 composite as the working electrode. The potential differences between the steel-based working electrodes and the liquid-aluminum-alloy reference electrode were measured for 85 h throughout the whole experiment, including the heating and cooling period. The experiments were performed at 850 °C. The determination of the high-temperature open circuit potential (ECorr) in reference to the liquid aluminum alloy was carried out via potentiodynamic polarization. The polarization-related changes in the impedance characteristics were evaluated by the correlation of impedance responses before and after the polarization. The addition of 40 vol% TiO2 resulted in a reduction in the potential of the steel-TiO2 composite and led to the formation of a more uniform electrode-electrolyte interface. The reaction products on the surface of the working electrodes were investigated by means of SEM/EDS and XRD. They consisted of mixed oxides within the Fe-O, Ba-Fe-O and Ba-Cr-O systems.

Plerixafor enables successful hematopoietic stem cell collection in an extensively pretreated patient with testicular cancer.

Plerixafor is a reversible CXCR4 antagonist that leads to a rapid release of hematopoietic stem and progenitor cells (HPSCs) from the bone marrow into the peripheral blood by interfering with the CXCL12-CXCR4 interaction. Based on two multicenter phase III studies, plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) was approved by the Food and Drug Administration for autologous HPSC mobilization in patients with multiple myeloma and non-Hodgkin's lymphoma. We report the case of a 26-year-old man with testicular cancer who was extensively pretreated and failed to mobilize a sufficient number of HPSCs after cytotoxic chemotherapy and the administration of G-CSF and pegylated G-CSF (PEG-G-CSF). Using a combination of plerixafor, G-CSF and PEG-G-GSF after chemotherapy, a sufficient number of HPSCs could be collected for the support of 3 sequential high-dose therapies. The patient achieved a complete and uncomplicated engraftment following each cycle of HPSC-supported high-dose therapy. Patients suffering from advanced germ cell cancer may be another group that benefits from the use of plerixafor, which to date has only been approved for the treatment of multiple myeloma and lymphoma. To our knowledge, this is the first case report of successful mobilization of HPSCs with plerixafor in a patient with testicular cancer.

Corrosion-Resistant Steel-MgO Composites as Refractory Materials for Molten Aluminum Alloys.

In this study, a novel metal matrix composite based on 60 vol% 316L stainless steel and 40 vol% MgO manufactured by powder metallurgy technology was developed. The corrosion resistance of the developed steel-MgO composite material against molten aluminum alloy AlSi7Mg0.3 was investigated by means of wettability tests and long-term crucible corrosion tests. The wettability tests were carried out using the sessile drop method with the capillary purification technique in a hot-stage microscope (HSM). Static corrosion tests were performed in molten aluminum alloy at 850 °C for 168 h to evaluate the impact of pre-oxidation of the composite surface on the corrosion resistance. The pre-oxidation of steel-MgO composites was carried out at 850 and 1000 °C for 24 h, based on preliminary investigations using thermogravimetry (TG) and dilatometry. The influence of the pre-oxidation on the composite structure, the corrosion resistance, and the phase formation at the interface between the steel-MgO composite and aluminum alloy was analyzed using SEM/EDS and XRD. The impact of the steel-MgO composite material on the composition of the aluminum alloy regarding the type, size, and quantity of the formed precipitations was investigated with the aid of ASPEX PSEM/AFA and SEM/EBSD. It was revealed that the pre-oxidation of the steel-MgO composite at 1000 °C induced the formation of stable MgO-FeO solid solutions on its surface, leading to a significant increase of long-term corrosion resistance against the liquid aluminum alloy.

Pharmacokinetic evaluation of palifermin for mucosal protection from chemotherapy and radiation.

INTRODUCTION: Oral mucositis, one of the major side effects of chemotherapy and irradiation, is still a burden of modern oncology. The keratinocyte growth factor (KGF) palifermin has been approved as a new, targeted therapy for the prevention of severe oral mucositis. AREAS COVERED: The authors review the literature on pharmacokintetics and clinical use of palifermin in patients with hematological malignancies and solid tumors for the prevention of chemo- and radiation-induced mucositis by using the PubMed database and additional literature where applicable. The article includes in vitro data, clinical trials as well as case reports regarding dosage, administration schedule, efficacy and adverse events. EXPERT OPINION: There is sufficient data for a beneficial effect of palifermin prophylaxis for patients with hematological cancers receiving high-dose chemotherapy and total body irradiation as well as patients with head and neck cancer receiving combined irradiation and chemotherapy. In less mucotoxic regimens, dose and schedule of palifermin to achieve protection from mucositis are less well defined. The balance of benefit and unwanted effects has to be evaluated and weighed for individual chemotherapy regimens and patient groups. Further research on the prevention of mucositis should aim to determine the patient's individual risk to develop severe mucositis.

Natalizumab and impedance of the homing of CD34+ hematopoietic progenitors.

BACKGROUND: Treatment with natalizumab, an antibody blocking the α4-integrin, is associated with increased numbers of circulating CD34+ cells in the peripheral blood of patients with multiple sclerosis. OBJECTIVE: To determine whether natalizumab mobilizes CD34+ cells from or inhibits homing to the bone marrow (BM). DESIGN: Fifty-two patients with relapsing-remitting multiple sclerosis treated with natalizumab were included. Flow cytometric analyses; polymerase chain reaction assays for JC (John Cunningham) virus DNA detection; and adhesion, migration, and apoptosis assays of immunomagnetically enriched peripheral blood and BM CD34+ cells were conducted. A comparison was made with CD34+ cells from granulocyte colony-stimulating factor-mobilized peripheral blood or steady-state BM of age- and sex-matched healthy donors. RESULTS: We found adhesion and migration of peripheral blood-derived CD34+ cells to be reduced. In BM aspirates from natalizumab-treated patients, the cellularity, the proportion, and the adhesive capacity of CD34+ cells were normal. The JC virus was undetectable. CONCLUSIONS: Natalizumab mediates an increase in circulating CD34+ cells by interfering with homing to the BM. Thus, CD34+ cells appear unlikely to represent a source mobilizing JC virus out of the BM in patients treated with natalizumab.

Immune mediators in patients with acute diabetic foot syndrome.

OBJECTIVE Subclinical inflammation is an important risk factor for type 2 diabetes and diabetes complications. However, data on the association between inflammation and acute diabetic foot syndrome are scarce. The aim of this study was to compare systemic immune mediators in diabetic patients with and without an ulcer and to identify modulating factors. RESEARCH DESIGN AND METHODS Circulating levels of acute-phase proteins, cytokines, and chemokines were measured in diabetic patients with an ulcer (n = 170) and without an ulcer (n = 140). Of the patients, 88% had type 2 diabetes. RESULTS Patients with an acute foot ulcer had higher levels of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, macrophage migration inhibitory factor, macrophage inflammatory protein-1alpha, and interferon-gamma-inducible protein-10 as well as lower levels of RANTES (regulated on activation normal T-cell expressed and secreted) (all P < 0.01). No differences were found for IL-8, IL-18, and monocyte chemoattractant protein-1. Most of these associations persisted after adjustment for demographic and anthropometric data, metabolic confounders, and diabetes complications. In multivariate models, size of ulcer according to the University of Texas classification but not the grade of infection was independently associated with three markers of subclinical inflammation (CRP, IL-6, and fibrinogen). CONCLUSIONS We demonstrate in our cross-sectional study that acute foot ulcers and their severity are associated with a marked upregulation of acute-phase proteins, cytokines, and chemokines independently of the concomitant infection. Further studies should investigate whether an activation of the immune system precedes the development of foot ulcer and whether anti-inflammatory therapies might be effective.