Long-term results of allogeneic peripheral blood hematopoietic stem cell transplantation for severe aplastic anemia

ObjectiveAplastic anemia (AA) is a life-threatening disorder and may be associated with significant morbidity and mortality Currently, the first treatment option is allogeneic hematopoietic stem cell transplant (allo-HSCT) for patients younger than 40 years. Bone marrow is recommended as the stem cell source due to less graft versus host disease (GVHD) risk and better outcomes than peripheral blood (PB)-derived stem cell. The aim of this study is to share the data of AA patients who have underwent PB-derived allo-HSCT in our bone marrow transplantation center.MethodsTwenty-seven patients who underwent PB-derived allo-HSCT from human leukocyte antigen matched sibling donors were analyzed retrospectively.ResultsThe median follow-up time was 95.2 months (range, 4.8–235 months). The 10-year survival was 89 %. The median neutrophil and platelet engraftment time was 11 days (range, 9–16 days) and 13 days (range, 11–29 days), respectively. Primary platelet engraftment failure was observed in 1 patient (3.7 %). Acute and chronic GVHD observed in 2 (7.4 %) and 3 (11.1 %) patients, respectively. Neutropenic fever was observed in 13 (44.8 %) of patients until the engraftment after allo-HSCT. One patient died due to CMV infections, two died due to septic shock secondary to fungal infection.ConclusionAlthough there is no prospective data directly comparing BM with PB as stem cell source in AA, observational studies indicates better OS with BM. PB can be used in certain situations such as higher risk for graft failure and donor preference. This study demonstrated that PB-derived stem cell seems to be a reasonable alternative to BM.     

Determination of cut‐off titers and agreement between immunofluorescence and immunoblotting methods for detecting antinuclear antibodies in children

Detection of antinuclear antibodies (ANA) is a diagnostic adjunct in patients with suspected autoimmune connective tissue diseases, and various detection methods are in use. The aim of this study was to analyze the agreement between the ANA immunoflourescence (IF) and immunoblotting (IB) methods and determine cut‐off for children subjects in a laboratory setting. We evaluated 729 serum samples that were analyzed by both ANA IF and IB. The results were evaluated by χ² test and, for agreement, κ index was used. Frequencies determined for both 1:40–1:100 cut‐off titers of ANA IF in relation to IB testing supported the idea that 1:100 starting dilution should be recommended in children subjects for ANA IF method and antigen specific immunoblot testing was needed, especially for some of the ANA IF negative samples. Agreement between the two methods, especially with homogenous, granular, and nucleolar ANA IF patterns, was statistically significant. J. Clin. Lab. Anal. 24:230–236, 2010. © 2010 Wiley‐Liss, Inc.     

Extracorporeal photoimmunotherapy for the treatment of steroid refractory progressive chronic graft-versus-host disease

BACKGROUND: Chronic graft-versus-host disease (cGVHD) can arise frequently as a late complication after allogeneic hematopoietic cell transplantation. Patients with extensive disease to date require intensive and long-term immuno-suppression. We aimed to share our single center experience using extracorporeal photoimmunotherapy (ECP) in our steroid refractory extensive cGVHD patients. PATIENTS AND METHODS: Eight patients with a median age 42 (range, 17-43) and M/F: 2/6 were treated with ECP (UVAR XTS) on 2 consecutive days every 2-4 weeks until resolution of GVHD over a period of 6-15 months concomitantly with immunosuppressive agents. Beyond extensive steroid refractory cutaneous cGVHD, three patients had also bronchiolitis obliterans (BO). Skin scores were assessed by an experienced dermatologist. Clinical, laboratory and radiological findings after 4 months of ECP were accepted as response criteria. The patients received in this almost fully automated system mean 261.4 ml buffy-coat was processed within 193 min using UVADEX sterile solution. RESULTS: After a median of 12 cycles of treatment, 6 patients showed a favorable response. ECP was tolerated well only one patient developed Gr4 thrombocytopenia and another patient had a massive GIS bleeding due to an esophageal tear. Reduction in cholestatic parameters was observed in patients with liver cGVHD, improvement in respiratory functions and CT evaluations in two, and reduction in immunosuppressive requirement in all patients. The most impressive result was the reduced need for hospitalization of these patients and improvement of skin lesions. All but one of the skin biopsy scores was also better after ECP. CONCLUSION: As extensive cGVHD is a life devastating disorder, every attempt to improve the quality of life should be evaluated carefully. Our findings suggest that ECP is a safe and effective adjunctive therapy for steroid refractory extensive cGVHD of the skin. ECP will find a place both for the treatment and may be for the prevention of GVHD as well.     

Describing Functioning in People Living With Spinal Cord Injury in Switzerland: A Graphical Modeling Approach

Objective

To describe functioning in people living with spinal cord injuries (SCI) in Switzerland.

Application of DNA Chip Scanning Technology for Automatic Detection of Chlamydia trachomatis and Chlamydia pneumoniae Inclusions

Chlamydiae are obligate intracellular bacteria that propagate in the inclusion, a specific niche inside the host cell. The standard method for counting chlamydiae is immunofluorescent staining and manual counting of chlamydial inclusions. High- or medium-throughput estimation of the reduction in chlamydial inclusions should be the basis of testing antichlamydial compounds and other drugs that positively or negatively influence chlamydial growth, yet low-throughput manual counting is the common approach. To overcome the time-consuming and subjective manual counting, we developed an automatic inclusion-counting system based on a commercially available DNA chip scanner. Fluorescently labeled inclusions are detected by the scanner, and the image is processed by ChlamyCount, a custom plug-in of the ImageJ software environment. ChlamyCount was able to measure the inclusion counts over a 1-log-unit dynamic range with a high correlation to the theoretical counts. ChlamyCount was capable of accurately determining the MICs of the novel antimicrobial compound {"type":"entrez-protein","attrs":{"text":"PCC00213","term_id":"1245601053","term_text":"PCC00213"}}PCC00213 and the already known antichlamydial antibiotics moxifloxacin and tetracycline. ChlamyCount was also able to measure the chlamydial growth-altering effect of drugs that influence host-bacterium interaction, such as gamma interferon, DEAE-dextran, and cycloheximide. ChlamyCount is an easily adaptable system for testing antichlamydial antimicrobials and other compounds that influence Chlamydia-host interactions.     

Two versus three day upfront use of granulocyte-colony stimulating factor in healthy bone marrow donors for pediatric bone marrow transplantation

In order to decrease donors’ exposure to granulocyte-colony stimulating factor (G-CSF), we compared the effect of two versus three days of G-CSF priming on CD34+ yield in bone marrow (BM) harvest. Although the number of BM-CD34+ cells was higher in 3 day G-CSF priming, we achieved the same number of CD34+ cells per recipient’s weight in 2 day G-CSF priming group, too. In addition, the number of total nucleated cells (TNC) harvested from BM were similar with two or three day regimen. But mononuclear cells (MNC) of the BM graft was higher in the 3 day G-CSF priming group. Similar to CD34+ cell numbers, BM harvest yielded similar TNC, and MNC numbers per kilogram of the recipient. We also found that, young donors (≤10 year) had more peripheral blood MNC, bone marrow MNC and CD34+ cell numbers. Another interesting finding of this study was obtaining adequate number of peripheral blood stem cells for leukapheresis with three day G-CSF administration. Since engrafment times were also similar in two groups, we concluded that 2-days G-CSF priming was resulted in sufficient mobilization of BM stem cells.     

Developmental and sex differences in somatosensory perception--a systematic comparison of 7- versus 14-year-olds using quantitative sensory testing

There are controversial discussions regarding developmental- and sex-related differences in somatosensory perception, which were found, eg, when comparing younger children (6–8 years), older children (9–12 years), and adolescents (13–16 years) using quantitative sensory testing (QST). The aim of our current study was to systematically assess the impact of age and sex using the QST protocol of the German Research Network on Neuropathic Pain (DFNS). QST, including thermal and mechanical detection and pain thresholds, was assessed in 86 healthy 7-year-old children (42 girls and 44 boys) and 87 healthy 14-year-old adolescents (43 girls and 44 boys). The sample size was calculated a priori to detect medium-sized effects as found in the previous studies with adequate power. Developmental and sex differences were tested using univariate analysis of variance. Children were more sensitive to most pain stimuli, except cold pain stimuli, compared with adolescents, but did not differ in mechanical and thermal detection thresholds except in regard to cold stimuli. Sex had an impact only on warm detection, with girls being more sensitive. There were no interactions between age and sex. In conclusion, developmental changes during the puberty appear to influence pain perception, whereas sex effects in childhood are negligible. At present, it is not clear what brings about the differences between adult men and women that are apparent in epidemiological studies. Our results contradict the hypothesis that differences in peripheral nerve-fiber functioning underlie sex effects.     

Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development

Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated in the medulla and contribute to the establishment of self-tolerance. However, how the medullary accumulation of tDCs is regulated and involved in self-tolerance is unclear. We show that the chemokine receptor XCR1 is expressed by tDCs, whereas medullary thymic epithelial cells (mTECs) express the ligand XCL1. XCL1-deficient mice are defective in the medullary accumulation of tDCs and the thymic generation of naturally occurring regulatory T cells (nT reg cells). Thymocytes from XCL1-deficient mice elicit dacryoadenitis in nude mice. mTEC expression of XCL1, tDC medullary accumulation, and nT reg cell generation are diminished in Aire-deficient mice. These results indicate that the XCL1-mediated medullary accumulation of tDCs contributes to nT reg cell development and is regulated by Aire.