Morphological and functional characteristics of rat steady state peritoneal dendritic cells.

Dendritic cells (DC) are present in lymphoid organs and also in many non-lymphoid tissues. In this study, DC in the steady state peritoneal cavity of rats were identified morphologically and functionally. Approximately 1% of the peritoneal cells are DC. On cytocentrifuge preparations these cells had the same characteristics as lymph node and spleen DC: they had an irregular outline, all were strongly MHC class II positive and had acid phosphatase activity in a spot in a juxtanuclear position. Also ultrastructurally, peritoneal DC were similar to DC isolated from lymph node and spleen. Enrichment of peritoneal DC, using overnight culture and a Nycodenz gradient, resulted in a highly purified DC fraction. Functionally, peritoneal DC appeared to be very potent antigen-presenting cells, far more potent than peritoneal macrophages, which had an inhibitory rather than an accessory function.     

Cross-diagnostic validity of the SF-36 physical functioning scale in patients with stroke, multiple sclerosis and amyotrophic lateral sclerosis: a study using Rasch analysis.

OBJECTIVE: The aim of this study was to investigate unidimensionality and differential item functioning of the SF-36 physical functioning scale (PF10) in patients with various neurological disorders. Patients: Patients post-stroke (n = 198), with multiple sclerosis (n = 151) and amyotrophic lateral sclerosis (n = 193) participated. METHODS: Unidimensionality of the PF10 within the patient groups was investigated by performing a separate Rasch analysis for each group. Differential item functioning was investigated in a pooled Rasch analysis of the 3 groups. RESULTS: Within each group, all items fitted the Rasch model, except the "bathing/dressing" item in the amyotrophic lateral sclerosis group. The pooled analysis showed inadequate fit to the Rasch model for one item ("walking several hundred metres"). Of the other 9 fitting items, 5 showed differential item functioning for stroke vs multiple sclerosis and amyotrophic lateral sclerosis, while no differential item functioning was found between multiple sclerosis and amyotrophic lateral sclerosis. CONCLUSION: All items of the PF10, except one for the amyotrophic lateral sclerosis group, form a unidimensional scale, supporting the use of a sum score as a measure of physical functioning within these diagnostic groups. When comparing the data of patients after stroke, with that of patients with multiple sclerosis and/or amyotrophic lateral sclerosis patients, adjustments for differential item functioning are required.     

T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis

Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. “Haploidentical expert” centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes (“haploidentical regular”, “haploidentical expert” and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10⁻⁵) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.     

Allogeneic CD34-enriched peripheral blood stem cell transplantation in a patient with paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of haematopoietic stem cells associated with a somatic mutation in the phosphatidylinositol glycan complementation class A (PIG-A) gene. The only curative option is an allogeneic stem cell transplant (SCT), although treatment is hazardous. A 46-year-old male patient with PNH and obvious signs of severe, progressive haemolysis was transplanted in July 2002 with highly purified CD34 T-cell depleted peripheral blood stem cells from his HLA-identical brother. Prior to transplantation, the PNH was resistant to immunosuppressive therapy. The patient received 6.1 x 10(6)/kg bodyweight CD34-positive cells with a proportion of CD3-positive cells of 0.81 x 10(4)/kg bodyweight. After engraftment, 12 days post transplant (neutrophils>1.0/nl) the patient's physical condition steadily improved and parameters of haemolysis decreased. No glycophosphatidylinositol-deficient cells in peripheral blood could be detected by flow cytometry 40 and 100 days after transplant. We conclude that PNH may be cured by allogeneic CD34-enriched SCT from a sibling donor attempting to avoid acute GVHD and to reduce cumulative organ toxicity by using this transplantation modality.     

Relevance and dynamics of myelofibrosis regarding hematopoietic reconstitution after allogeneic bone marrow transplantation in chronic myelogenous leukemia--a single center experience on 160 patients

A retrospective single center study was performed on 516 trephine biopsies derived from 160 patients with stable phase Ph+-CML and allogeneic BMT. Following morphometric quantification of reticulin-collagen fibers we tried to elucidate (1) the dynamics of bone marrow fibrosis in the post-transplant period; and (2) the influence of manifest myelofibrosis on relevant engraftment parameters. An evaluation of fiber density at standardized endpoints after BMT was carried out on a selected cohort of 124 patients (399 biopsy specimens). A manifest myelofibrosis (more than a three-fold increase compared to the normal fiber content) before BMT was found in 26% of our patients. Concentrating on bone marrow areas with reconstituting hematopoiesis, several findings emerged. Pretransplant myelofibrosis was associated with an initial regression following BMT, but insidiously recurred in the areas of regenerating hematopoiesis or developed in a few patients without increased pregraft fibers during the post-transplant period (mean observation time more than 4 months). Severe acute GVHD (grades III and IV) was significantly correlated with a greater amount of reticulin fibers in the early post-transplant period (9 to 30 days after BMT). Regarding engraftment parameters, a significant delay was detectable in the time to achieve transfusion independence for the patients with manifest myelofibrosis compared to those without pre-transplant fiber increase.     

Relation of an interleukin-23 receptor gene polymorphism to graft-versus-host disease after hematopoietic-cell transplantation

Polymorphisms in cytokine genes can influence immune responses and inflammation and thereby affecting the outcome of hematopoietic stem-cell transplantation. We analyzed a single-nucleotide polymorphism in the gene for the interleukin-23 receptor (IL-23R) (1142G>A) in a cohort of 221 transplant recipients and their human leukocyte antigen (HLA)-identical sibling donors and in a second cohort of 186 transplant recipients and their HLA-identical unrelated donors. Genotypes were tested for an association with graft-versus-host disease (GVHD) by multivariate analysis. The donor's IL-23R genotype was significantly associated with a reduced risk of acute GVHD in both cohorts for patients after transplant. Analysis of all 407 transplant recipients showed that IL-23R (1142G>A, Arg381Gln) genotype of the donor was associated with a decreased risk of grades 2-4 acute GVHD (31.6 compared to 51.0%, P=0.02) and grades 3-4 severe acute GVHD (3.9 compared to 23.4%, P=0.003). Death in remission was significantly lower in patients transplanted from donors with variant IL23-R (11.7 versus 27.7%, P=0.028), whereas overall survival or relapse rates were not influenced significantly by the IL-23R genotype. Among recipients of hematopoietic cells from HLA-identical donors, the IL-23R (Arg381Gln) gene variant on the donor side has a protective effect on the occurrence of acute GVHD in recipients after transplantation.