Application of mesenchymal stem cells (MSC) enables a novel approach to the therapy of graft- vs-host disease (GVHD) after hematopoietic stem cell transplantation. Herein we present our preliminary ...experience with the use of allogeneic bone marrow‒derived MSC in 9 pediatric patients after hematopoietic transplantation complicated by severe acute or chronic GVHD (aGVHD, cGVHD) resistant to steroids and second-line immunosuppressants. The MSC therapy was applied concurrently with immunosuppressive treatment in 5 patients as a single infusion, in four patients as 2-6 infusions. The median dose of cells per infusion was 1.9 × 106/kg of recipient body weight (range, 0.1–6.5 × 106/kg). The median quantity of cells applied to patients was 1.2 × 106/kg (range, 0.2–30.9 × 106/kg). We did not observe any adverse symptoms of MSC therapy. Overall, partial, or complete remission (PR and CR, respectively) was obtained in 56% of patients after the first MSC infusions, and 44% after completing therapy. In those with skin involvement 50% achieved permanent CR, 38% in those with gastrointestinal manifestations, and 33% in those with liver GVHD. Three patients with overlap syndrome had amelioration, but none had permanent remission. Long-term improvement after consecutive MSC doses was observed in 3 patients. In the 4- to 8-year follow-up, 3 patients are alive and 2 have attained permanent remission. Six patients died during follow-up: 4 with aGVHD and 2 with infectous complications. Co-treatment of streoid-resistant GVHD with MSC and conventional immunosuppression can improve the outcome, although therapy regimens remain to be established.
•Mesenchymal stem cells (MSC) provide effective graft-vs-host disease therapy.•MSC application should be based on a repeated-infusion schedule.•MSC therapy shows better results in acute graft-vs-host disease.•The best improvement can be attained in skin and intestinal involvement.
Central Poland is situated in the centre of the Late Pleistocene and Holocene “European aeolian sand belt”. This area has the highest frequency of round, mat grains of all Europe, due to intense ...aeolian abrasion. Aeolian processes were very active during several glaciations, but the changes in aeolian activity in the course of an entire glaciation can be studied only for the Vistulian (Weichselian, Wisconsinan). The reason is that a continuous blanket of glacial sediments either covered, or partly eroded older aeolian sediments in central Poland during the Wartanian (Saalian II). Aeolian processes began just after deglaciation and became intense under the periglacial conditions of the Late Wartanian and the whole Vistulian. The evolution of these processes is reconstructed, especially for the interval of the highest and most effective aeolian activity, i.e. the Late Plenivistulian (Oxygen Isotope Stage 2: the coldest stage of the last glaciation). A model of the sequence of periglacial aeolian events during an entire glaciation is presented. This model may be used for the reconstruction of older Pleistocene cycles of high periglacial aeolian activity.
The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 ...pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10(6)/kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.
According to the published report on current practice of hematopoietic SCT in Europe, high-dose therapy (HDT) with autologous stem cell support is a standard of care in paediatric patients with high ...risk (HR) or relapsed Ewing's sarcoma (ES). Randomized trials, however, have not confirmed the value of this procedure yet. In this retrospective analysis we intended to evaluate the role of HDT as a consolidation therapy in first remission of ES. A total of 102 patients were included in the analysis and divided according to the following risk factors: metastatic disease at presentation, feasibility of surgery and histological response after induction. Forty-one patients were classified as standard risk (SR) patients, while the remaining 61 children, with at least one risk factor, were classified as HR patients. HR group patients were non-randomized and qualified according to the decision of the local clinician to give a conventional consolidation (CC) or to perform high-dose chemotherapy and radiotherapy in selected patients. Twenty-six children were given CC while 35 patients were treated with HDT. The HDT consisted of oral BU 4 mg/kg p.o. in divided doses daily for 4 days (total dose 16 mg/kg) followed by melphalan 140 mg/m(2) i.v. on day -2. Probability of relapse-free survival (RFS) in median observation time was significantly worse in HR patients who were given CC therapy as compared with children with HR features receiving high-dose chemotherapy (0.27 vs 0.66 (P = 0.008); OS 0.31 vs 0.71 (P = 0.007), respectively). Patients from the SR group had a probability of RFS of 0.72 and OS of 0.75, and the difference between SR and HR patients after HDT was NS (P = 0.37). Our observation confirms that the consolidation of the first-line treatment with BU and melphalan improves the outcome in ES patients with HR features.
The aim of the study was to assess the markers of oxidant-antioxidant status in excess body mass index (BMI) persons with and without the obstructive sleep apnea syndrome (OSAS). In overweight ...(BMI-1: 25.0-29.9 kg/m(2)) control and OSAS and obese (BMI-2: 30.0-34.9 kg/m(2)) control and OSAS subjects with no acute or chronic disorder the following markers were determined: concentration of plasma total antioxidant status, TAS, (Randox); activity of erythrocyte Cu, Zn-superoxide dysmutase, SOD, (Randox); plasma concentration of thiobarbituric acid reacting substances, TBARS, (Yagi method). BMI-1-OSA presented decreased SOD, compared with the BMI-1-C group (P=0.006). BMI-2-OSA showed both SOD (P=0.002) and TAS (P=0.047) decreased, and elevated TBARS (P=0.03) compared with the BMI-2-C group. There was a positive correlation between TAS & SOD and a negative one between TAS & TBARS in the BMI-1-C group. In BMI-2-C, a negative correlation between TAS & TBARS was observed. We conclude that OSAS decreases the blood antioxidant status in high BMI persons and may change the relationship between oxidative stress markers.
Chronic granulomatous disease (CGD) is a primary immunodeficiency resulting in life-threatening infections and inflammatory complications. Allogeneic hematopoietic cell transplantation (allo-HCT) can ...cure the disease, but the indication to transplant remains controversial. We performed a retrospective multicenter study of 712 patients with CGD who underwent allo-HCT transplantation from March 1993 through December 2018. We studied 635 children (aged <18 years) and 77 adults. Median follow-up was 45 months. Median age at transplantation was 7 years (range, 0.1-48.6). Kaplan-Meier estimates of overall survival (OS) and event-free survival (EFS) at 3 years were 85.7% and 75.8%, respectively. In multivariate analysis, older age was associated with reduced survival and increased chronic graft-versus-host disease. Nevertheless, OS and EFS at 3 years for patients ≥18 years were 76% and 69%, respectively. Use of 1-antigen-mismatched donors was associated with reduced OS and EFS . No significant difference was found in OS, but a significantly reduced EFS was noted in the small group of patients who received a transplant from a donor with a >1 antigen mismatch. Choice of conditioning regimen did not influence OS or EFS. In summary, we report an excellent outcome after allo-HCT in CGD, with low incidence of graft failure and mortality in all ages. Older patients and recipients of 1-antigen-mismatched grafts had a less favorable outcome. Transplantation should be strongly considered at a younger age and particularly in the presence of a well-matched donor.
Adipocytokines in sleep apnea syndrome Wysocka, E; Cofta, S; Dziegielewska, S ...
European journal of medical research,
12/2009, Letnik:
14 Suppl 4, Številka:
Suppl 4
Journal Article
Recenzirano
Odprti dostop
Biomarkers of adipose tissue may affect glucose and lipid metabolism and present pro-inflammatory properties, thus could be involved in the pathobiochemistry of cardiovascular disease (CVD). The ...coexistence of sleep apnea syndrome (OSA) and metabolic risk factors of CVD is worth explaining. The aim of the study was to compare the serum adipocytokines in subjects with and without OSA, who had all elevated body mass index (BMI).
Overweight (BMI: 25.0-29.9 kg/m2) and obese (BMI: 30.0-39.9 kg/m2) OSA-suspected Caucasian males, aged 30-63, with no acute disease or chronic disorder underwent polysomnographic evaluation to select OSA-positive (AHI > or = 5) and OSA-negative (AHI <5) subjects. Four subgroups were created of 18 persons each: Over(weight)-OSA-Neg, Over-OSA-Pos, Obese-OSA-Neg, Obese-OSA-Pos. In all subjects, plasma carbohydrate and lipid metabolism parameters, and serum uric acid, resistin and leptin concentrations were determined.
A decreased resistin level was observed in Over-OSA-Pos vs. Over-OSA-Neg subjects (P=0.037) as well as in Obese-OSA-Pos vs. Obese-OSA-Neg (P=0.045). No differences in leptin concentrations were observed. A positive correlation between leptin and BMI was in both overweight subgroups and a negative one between resistin and fasting glucose was in both obese subgroups.
OSA may decrease the serum resistin level in subjects with excess body mass and also may contribute to glucose metabolism, but has no influence on the leptin level.
Hematopoietic stem cell transplantation (HSCT) represents a curative treatment for patients with severe combined immunodeficiency (SCID), a group of monogenic immune disorders with an otherwise fatal ...outcome.
We performed a comprehensive multicenter analysis of genotype-specific HSCT outcome, including detailed analysis of immune reconstitution (IR) and the predictive value for clinical outcome.
HSCT outcome was studied in 338 patients with genetically confirmed SCID who underwent transplantation in 2006-2014 and who were registered in the SCETIDE registry. In a representative subgroup of 152 patients, data on IR and long-term clinical outcome were analyzed.
Two-year OS was similar with matched family and unrelated donors and better than mismatched donor HSCT (P < .001). The 2-year event-free survival (EFS) was similar in matched and mismatched unrelated donor and less favorable in mismatched related donor (MMRD) HSCT (P < .001). Genetic subgroups did not differ in 2-year OS (P = .1) and EFS (P = .073). In multivariate analysis, pretransplantation infections and use of MMRDs were associated with less favorable OS and EFS. With a median follow-up of 6.2 years (range, 2.0-11.8 years), 73 of 152 patients in the IR cohort were alive and well without Ig dependency. IL-2 receptor gamma chain/Janus kinase 3/IL-7 receptor–deficient SCID, myeloablative conditioning, matched donor HSCT, and naive CD4 T lymphocytes >0.5 × 10e3/μL at +1 year were identified as independent predictors of favorable clinical and immunologic outcome.
Recent advances in HSCT in SCID patients have resulted in improved OS and EFS in all genotypes and donor types. To achieve a favorable long-term outcome, treatment strategies should aim for optimal naive CD4 T lymphocyte regeneration.
The aim of this study was to evaluate the correlation between the stage of cystic fibrosis and the intensity of accompanying morphological changes--including transmission electron microscopy--within ...bronchial mucosa. The stage of the disease was assessed on the basis of clinical status and radiological and endoscopic examination. We focused on morphological changes in epithelial cells, the presence of metaplasia and/or dysplasia, the type of inflammatory infiltrate, and the presence of epithelial ulcerations, thickening of epithelial basement membrane and collagenization of lamina propria. We found two clinically different patients groups. The first one was in a poor clinical condition, advanced inflammatory fiberoptic bronchoscopy and radiological changes, multiple exacerbations, and with chronic inflammation and only focal appearance of ciliated epithelium. Moreover, squamous cell metaplasia and dysplasia was diagnosed in 3 and 4 cases, respectively. The other group, in a better clinical condition, had normal BMI and small changes on chest Xray. In this group the diagnosis of cystic fibrosis was made at later age. Two patients from this group displayed features of acute phase; ciliated epithelium was covering the whole sample. After statistical analysis, we found a correlation between the clinical course and the morphological changes in bronchial mucosa. Bronchial ulcerations, squamous cell metaplasia and dysplasia were found in the group with the more severe clinical course.
Cystic fibrosis (CF) is a multisystem autosomal recessive disorder caused by the mutation of a single gene that encodes for the CF transmembrane regulator protein. Clinically, CF is characterized by ...chronic pulmonary infection, pancreatic insufficiency, and excessive losses of sweat electrolytes. Along with lung function, nutritional status appears one of the most important prognostic indicators in CF patients. In this study we examined the relationship between nutritional status and pulmonary function in adult CF patients. A group of 39 CF patients (mean age 23.9 +/-3.7 years) was studied. The mean value of body mass index (BMI) was 19.5 +/-2.9kg/m(2) (12.8-24.9kg/m(2)). The patients were grouped according to the presence or absence of malnutrition. Malnutrition was established in 11 patients (28.2%), 5 patients suffered from severe malnutrition. 28 patients (71.8%) had a normal nutritional status, but according to ESPEN guidelines, 9 of those patients were at risk of malnutrition. Statistical analysis revealed a significant difference between malnourished and not malnourished patients with respect to FEV(1)% and FVC%. Moreover, the patients with malnutrition were significantly more frequently colonized by P. aeruginosa and fungi and less so by MSSA.
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