bluuebunny/crossref_metadata_2025_split huggingface dataset:
Children with myelodysplastic syndrome (MDS) and increasing mixed chimaerism after allogeneic stem cell transplantation have a poor outcome which can be improved by pre‐emptive immunotherapy
Authors: Bader Peter , Niemeyer Charlotte , Willasch Andre , Kreyenberg Hermann , Strahm Brigitte , Kremens Bernhard , Gruhn Bernd , Dilloo Dagmar , Vormoor Josef , Lang Peter , Niethammer Dietrich , Klingebiel Thomas , Beck James F. 
Published: February 2005

SummaryWe recently reported that virtually all children with acute leukaemia and myelodysplastic syndrome (MDS) who develop the phenotype of increasing mixed chimaerism (MC) after allogeneic stem cell transplantation (allo‐SCT) will relapse. We therefore performed a prospective, multi‐centre study focused on children with MDS (n = 65; advanced MDS = 44, refractory cytopenia = 21) after allo‐SCT in order to determine to what extent relapse can be prevented by pre‐emptive immunotherapy on the basis of increasing MC. Analyses of chimaerism in 44 patients with advanced MDS revealed 31 cases with complete chimaerism (CC)/low‐level MC/transient MC, 11 cases with increasing MC and two cases with decreasing MC. The same analyses in 21 MDS patients with refractory cytopenia revealed 17 cases with CC/low‐level MC, one case with increasing MC and three cases with decreasing MC. Pre‐emptive immunotherapy performed on each patient that showed increasing MC improved event‐free survival from 0%, as seen in prior studies, to 50%. We therefore conclude that pre‐emptive immunotherapy is an effective treatment option to prevent impending relapse in children with MDS after allo‐SCT.
Autocrine secretion of osteopontin results in degradation of IκB in Bcr‐Abl‐expressing cells
Authors: Vejda Susanne , Piwocka Katarzyna , McKenna Sharon L. , Cotter Thomas G. 
Published: February 2005

SummaryOsteopontin has been identified as a marker of metastasis formation and its increased expression has been correlated with the malignancy of cancer. In this study we provide evidence that increased expression of osteopontin may also be associated with progression of Bcr‐Abl‐expressing leukaemia cells. The Bcr‐Abl fusion protein, generated by the Philadelphia translocation, is the hallmark of chronic myeloid leukaemia (CML). CML exhibits clinically distinct phases. Advanced disease shows defective differentiation, bone marrow infiltration and drug resistance. The critical signalling mediating this disease progression is unknown. Increased aggressiveness of the disease has been correlated with elevated amounts of Bcr‐Abl. We generated a 32D cell line model to study the consequences of different expression levels of Bcr‐Abl. Osteopontin was identified by microarray analysis as highly upregulated in cells expressing elevated amounts of Bcr‐Abl. Moreover, in high Bcr‐Abl expressing cells, an additional 50 kDa isoform of osteopontin was detected. It was found that this protein was secreted and that myeloid progenitor cells also expressed appropriate receptors for autocrine activation. We demonstrated that secretion of osteopontin resulted in enhanced degradation of IκB, the inhibitor of NF‐κB. These data indicate a novel consequence of elevated Bcr‐Abl expression, which may contribute to the progression of CML.
Association of NAT and GST polymorphisms with non‐Hodgkin's lymphoma: a population‐based case–control study
Authors: Chiu Brian C.‐H. , Kolar Carol , Gapstur Susan M. , Lawson Terence , Anderson James R. , Weisenburger Dennis D. 
Published: February 2005

SummarySeveral chemicals have been associated with risk of non‐Hodgkin's lymphoma (NHL), many of which are substrates for N‐acetyltransferase (NAT) and glutathione S‐transferase (GST) enzymes. We investigated the association between polymorphisms in genes coding for these enzymes and NHL risk in a population‐based study (389 cases and 535 controls). NAT1 slow genotype was associated with a slightly increased risk in women [odds ratios (OR) = 1·4; 95% confidence interval (CI) = 0·9–2·3], but not in men. NAT2 slow genotype was not associated with risk in either sex. The two slow genotypes of NAT1 and NAT2 combined were associated with a minor increase of risk in women (OR = 1·4; 0·8–2·4). There was no association with the GSTM1 or GSTT1 null genotype in either sex, irrespective of histological subtypes. Individuals with GSTP1 Val homozygotes had non‐significant excessive risk of marginal zone lymphoma (OR = 1·8; 0·6–5·1) and ‘other’ B‐cell NHLs (OR = 1·6; 0·7–3·6), but lower risk of diffuse large B‐cell lymphoma (OR = 0·2; 0·1–0·96). Risk did not elevate with an increasing number of high‐risk GST alleles in either sex. In summary, although NAT1, NAT2, GSTM1, GSTT1, or GSTP1 polymorphisms do not appear to be associated with NHL risk overall, there might be gender‐specific and subtype‐specific associations that require confirmation.
Low‐grade primary central nervous system lymphoma in immunocompetent patients
Authors: Jahnke Kristoph , Thiel Eckhard , Schilling Andreas , Herrlinger Ulrich , Weller Michael , Coupland Sarah E. , Krümpelmann Ulrich , Stein Harald , Korfel Agnieszka 
Published: February 2005

SummaryPrimary central nervous system lymphomas (PCNSL) are usually diffuse large B‐cell non‐Hodgkin's lymphomas (NHL). Here we characterize the clinical presentation, course and outcome of patients with low‐grade PCNSL. Records of 332 patients screened for inclusion in three multicentre prospective trials were reviewed. Ten patients (3%) with a median age of 59 years and a median Karnofsky performance status of 70% were identified. Seven patients had B‐cell and three had T‐cell lymphoma. The median growth fraction was 4%. The radiological morphology was unusual for PCNSL in eight patients. Three patients underwent complete tumour resection, combined with chemotherapy in one patient and with chemotherapy plus local radiotherapy in another. Four patients received chemotherapy and three received chemotherapy plus whole‐brain irradiation, resulting in four complete remissions, two no‐change situations and one progressive disease. Patients had an overall survival (OAS) of 2–58+ months with a 2‐year OAS of 67%. Low‐grade PCNSL may differ from classical high‐grade PCNSL in its clinical features and radiological morphology. The clinical course may be variable and frequently more indolent than in classical PCNSL.
Targeting malignant B‐cell lymphoma with a humanized anti‐CD22 scFv‐angiogenin immunoenzyme‡
Authors: Krauss Jürgen , Arndt Michaela A.E. , Vu Bang K. , Newton Dianne L. , Rybak Susanna M. 
Published: February 2005

SummaryWe report on the generation and functional characterization of a humanized immunoenzyme comprising a stable humanized single chain Fv (scFv) with grafted specificity of the anti‐CD22 murine monoclonal antibody RFB4 and the human ribonuclease angiogenin (ANG). The fusion protein produced from transiently transfected mammalian Chinese hamster ovary cells could easily be purified to homogeneity, retained full ribonucleolytic activity, and efficiently killed CD22+ tumour cells with an IC50 of 56 nmol/l. In contrast, incubation of tumour cells with either ANG or scFv alone did not result in any cytotoxicity. Potent receptor‐mediated killing of target cells, expected lack of extracellular toxicity, predictable low immunogenic potential, and ease of production, suggest that this novel immunoenzyme has potential for the immunotherapy of CD22+ malignancies.
Activity of sirolimus in patients with myelodysplastic syndrome – results of a pilot study
Authors: Platzbecker U. , Haase M. , Herbst R. , Hänel A. , Voigtmann K. , Thiede C. H. , Mohr B. , Schleyer E. , Leopold T. , Orth M. , Hänel M. , Ehninger G. , Bornhäuser M. 
Published: February 2005

SummaryThe pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54–80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3–12 ng/ml. Sirolimus was administered for a median of 3·7 months (range 0·3–11 months). Three patients [1 × refractory anaemia with excess blasts (RAEB)‐2, 1 × RAEB‐1, 1 × refractory cytopenia with multilineage dysplasia] showed either a major (1 × platelet, 1 × neutrophil) or a minor (1 × erythroid, 2 × platelet) haematological response according to International Working Group criteria. Major side‐effects were hyperlipidaemia (n = 4), stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1). These data suggest that sirolimus has activity in a subset of patients with more advanced MDS.
Allogeneic peripheral blood stem cell graft composition affects early T‐cell chimaerism and later clinical outcomes after non‐myeloablative conditioning
Authors: Panse J. P. , Heimfeld S. , Guthrie K. A. , Maris M. B. , Maloney D. G. , Baril B. B. , Little M.‐T. , Chauncey T. R. , Storer B. E. , Storb R. , Sandmaier B. M. 
Published: February 2005

SummaryWe have studied the influence of cell subsets [CD34, CD3, CD4, CD8, CD14, CD20, natural killer (NK; CD3−/CD56+), NKT (CD3+/CD56+), DC1, and DC2 cells] of granulocyte colony‐stimulating factor mobilized peripheral blood stem cells (PBSC) on early T‐cell chimaerism and later clinical outcomes in 125 patients with haematological malignancies who received human leucocyte antigen (HLA)‐matched related grafts after non‐myeloablative conditioning. Conditioning consisted of 2 Gy total body irradiation (TBI) alone (n = 28), or 2 Gy TBI preceded by either 90 mg/m2fludarabine (n = 62) or planned autologous haematopoietic cell transplantation (HCT) (n = 35). Post‐transplant immunosuppression included mycophenolate mofetil and ciclosporin. Multivariate analysis showed that higher numbers of grafted NK cells predicted higher early T‐cell chimaerism (P = 0·03), while higher numbers of B cells were associated with better clinical outcomes and a higher risk for chronic graft‐versus‐host disease (P = 0·05). Higher numbers of CD14+cells were associated with worse overall survival (P = 0·03), while higher numbers of CD34+cells showed better survival (P = 0·03). The addition of fludarabine or autologous HCT predicted higher early T‐cell chimaerism (P = 0·001), while advanced donor age predicted lower chimaerism (P ≤ 0·02). Patients with aggressive diseases were at higher risk for relapse/disease progression, and shorter progression‐free and overall survival (P < 0·01). These results suggest that the dosing of certain cellular subsets of PBSC products can influence important outcomes post‐HCT after non‐myeloablative conditioning.
Persistence of recipient plasma cells and anti‐donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABO incompatible non‐myeloablative haematopoietic cell transplantation
Authors: Griffith L. M. , McCoy J. P. , Bolan C. D. , Stroncek D. F. , Pickett A. C. , Linton G. F. , Lundqvist A. , Srinivasan R. , Leitman S. F. , Childs R. W. 
Published: February 2005

SummaryDelayed donor erythropoiesis and pure red‐cell aplasia (PRCA) complicate major‐ABO mismatched non‐myeloablative allogeneic stem‐cell transplantation. To characterize these events, we analysed red‐cell serology and chimaerism in lymphohaematopoietic lineages, including plasma cells and B cells, in 12 consecutive major‐ABO incompatible transplants following cyclophosphamide/fludarabine‐based conditioning. Donor erythropoiesis was delayed to more than 100 days in nine (75%) patients including six (50%) who developed PRCA. During PRCA, all patients had persistent anti‐donor isohaemagglutinins and recipient plasma cells (5–42%), while myeloid and T cells were completely donor in origin. In contrast, B‐cell chimaerism was frequently full‐donor when significant anti‐donor isohaemagglutinins persisted. Four patients with early mixed haematopoietic chimaerism and the prolonged presence of anti‐donor isohaemagglutinins and recipient plasma cells developed delayed‐onset (>100 days post‐transplant) red cell transfusion dependence and PRCA after myeloid chimaerism converted from mixed to full donor. These findings confirm that donor‐erythropoiesis is impacted by temporal disparities in donor immune‐mediated eradication of recipient lymphohaematopoietic cells during major‐ABO incompatibility and suggest that plasma cells are relatively resistant to graft‐versus‐host haematopoietic effects.
Heterogeneity of the ɛγδβ‐thalassaemias: characterization of three novel English deletions
Authors: Rooks Helen , Bergounioux Jean , Game Laurence , Close James Paul , Osborne Cameron , Best Steve , Senior Tania , Height Susan , Thompson Richard , Hadzic Nedim , Fraser Peter , Bolton‐Maggs Paula , Thein Swee Lay 
Published: February 2005

SummaryWe have characterized three novel ɛγδβ‐thalassaemia deletions in three English families. Two of the deletions, 114 and 439 kb, removed the entire β‐globin gene complex, including a variable number of flanking olfactory receptor (HOR) genes. The 98‐kb deletion extended 90‐kb upstream of the ɛ gene to 8 kb upstream of the Gγ‐gene, leaving the γ,δ and β‐genes intact. The 439 kb deletion is the largest deletion reported so far to cause ɛγδβ‐thalassaemia; heterozygotes for this deletion were variably affected by neonatal haemolytic anaemia. Two of the deletions were de novo. Breakpoints of all three deletions occurred within regions of L1 or Alu repeats and contained short regions of direct homology between the flanking sequences, a feature that is likely to have contributed to the illegitimate recombinations.
Difference in absolute risk of venous and arterial thrombosis between familial protein S deficiency type I and type III. Results from a family cohort study to assess the clinical impact of a laboratory test‐based classification
Authors: Brouwer Jan‐Leendert P. , Veeger Nic J. G. M. , Schaaf Wim van der , Kluin‐Nelemans Hanneke C. , Meer Jan van der 
Published: February 2005

SummaryHereditary protein S (PS) deficiency type I is an established risk factor for venous thromboembolism. Contradictionary data on type III deficiency suggests a difference in risk between both types. We studied 156 first degree relatives (90% of eligible relatives) from type I deficient probands (cohort 1) and 268 (88%) from type III deficient probands (cohort 2) to determine the absolute risk of venous and arterial thromboembolism. Annual incidences of venous thromboembolism were 1·47 and 0·17 per 100 person‐years in deficient and non‐deficient relatives in cohort 1 [relative risk (RR) 8·9; 95% confidence interval (CI) 2·6–30·0], and 0·27 vs. 0·24 in cohort 2 (RR 0·9; 95% CI 0·4–2·2). Type III deficiency was demonstrated in 20% of non‐deficient relatives in cohort 1 and the annual incidence in this subgroup was 0·70 (RR 4·3;0·95–19·0). The cut‐off level of free PS to identify subjects at risk was 30%, the lower limit of its normal range (65%). PS deficiency was not a risk factor for arterial thromboembolism. In conclusion, type I deficiency was found to be a strong risk factor for venous thromboembolism, in contrast with type III deficiency. This was because of lower free PS levels in type I deficient subjects and a free PS cut‐off level far below the lower limit of its normal range.
Impact of chimaerism analysis and kinetics on allogeneic haematopoietic stem cell transplantation outcome after conventional and reduced‐intensity conditioning regimens
Authors: Michallet Anne‐Sophie , Fürst Sabine , Le Quoc Hung , Dubois Valérie , Praire Aline , Nicolini Franck , Thomas Xavier , Rafii Hanadi , Gebuhrer Lucette , Michallet Mauricette 
Published: February 2005

SummaryThis retrospective study aimed to analyse the impact on overall survival (OS) and event‐free survival (EFS) of chimaerism status and kinetics following allogeneic conventional and reduced‐intensity conditioning haematopoietic stem cell transplantation, and to compare this with the impact of other well‐known factors. We investigated the chimaerism status of 187 patients [84 females, 103 males; median age 39·5 years (range, 17–62 years)]. After transplantation, 121 patients (65%) presented full donor chimaerism (FDC) and 63 (34%) mixed chimaerism (MC). For MC, we divided the population into patients who presented regressive mixed chimaerism (RMC) (21 patients: 11%), stable mixed chimaerism (SMC) (20 patients: 11%) and progressive mixed chimaerism (PMC) (22 patients: 12%). At last follow‐up, 71 patients were alive and 116 had died (48% from disease progression and 52% from transplant‐related causes). With a mean follow‐up of 39·4 and 34·8 months, the 5‐year probabilities of OS and EFS for the total group were, respectively, 55% and 43%: 69·5% and 61% for FDC, 35·4% and 25% for RMC, 42·6% and 28·6% for SMC, and 21% and 10·4% for PMC (P < 0·0001 and P < 0·0001). Multivariate analysis only showed a significant impact of chimaerism status on OS, as well as acute and chronic graft‐versus‐host disease on EFS, with a trend for conditioning regimen.
Pilot study of reduced‐intensity conditioning followed by allogeneic stem cell transplantation from related and unrelated donors in patients with myelofibrosis
Authors: Kröger Nicolaus , Zabelina Tatjana , Schieder Heike , Panse Jens , Ayuk Francis , Stute Norbert , Fehse Natalja , Waschke Olga , Fehse Boris , Kvasnicka Hans Michael , Thiele Jürgen , Zander Axel 
Published: February 2005

SummaryA prospective pilot study was performed to evaluate the effect of reduced‐intensity conditioning with busulphan (10 mg/kg), fludarabine (180 mg/qm) and anti‐thymocyte globulin followed by allogeneic stem cell transplantation from related (n = 8) and unrelated donors (n = 13) in 21 patients with myelofibrosis. The median age of the patients was 53 years (range, 32–63). No primary graft failure occurred. The median time until leucocyte (>1·0 × 109/l) and platelet (>20 × 109/l) engraftment was 16 (range, 11–26) and 23 d (range, 9–139) respectively. Complete donor chimaerism on day 100 was seen in 20 patients (95%). Acute graft‐versus‐host disease (GvHD) grades II–IV and III/IV occurred in 48% and 19% of cases and 55% of the patients had chronic GvHD. Treatment‐related mortality was 0% at day 100 and 16% [95% confidence interval (CI): 0–32%] at 1 year. Haematological response was seen in 100% and complete histopathological remission was observed in 75% of the patients and 25% of the patients showed partial histopathological remission with a continuing decline in the grade of fibrosis. After a median follow‐up of 22 months (range, 4–59), the 3‐year estimated overall and disease‐free survival was 84% (95% CI: 67–100%).
Indoor allergens in settled school dust: a review of findings and significant factors
Authors: Tranter D. C. 
Published: February 2005

SummaryThe school environment can be an important site of exposure to cat, dog, dust mite, and cockroach allergens, which have been detected in the settled dust of many schools. The sizable body of research that has been published in recent years warrants careful examination. This review article informs clinicians, researchers, and other parties about the potential for exposure in the school environment, factors that affect allergen concentrations, and areas of future research. While average concentrations in schools were usually under risk levels for symptoms or sensitization, many studies reported at least one location where the concentrations exceeded these levels. Maintenance, mechanical, and administrative factors were related to allergen levels in schools. From a clinical perspective, the school environment in industrialized nations has a lower potential for exposure than the home environment, but schools are significant for allergic individuals whose home environment has been addressed to the extent feasible. From a public health perspective, the school environment should be considered as a target for primary and secondary prevention. It can be more practical and amenable to intervene on a single school than the hundreds of homes in a community. Future research should continue to evaluate which interventions are most practical and result in the greatest measurable improvements. In addition, research should further examine the relationship between allergen exposure in schools and health effects, in order to develop an accurate exposure assessment model and risk levels that are specific to the school environment.
The effect of treatment with montelukast on in vitro interleukin‐10 production of mononuclear cells of children with asthma
Authors: Stelmach I. , Majak P. , Jerzynska J. , Kuna P. 
Published: February 2005

SummaryBackground
The effects of leukotriene modifiers on IL‐10 production have not been studied in children with asthma.Objective
The primary objective of this study was to determine the changes in IL‐10 concentrations, clinical efficacy and peripheral blood eosinophil counts after treatment with montelukast.Methods
The study was conducted on 27 patients: 13 patients monoallergic to grass pollen during the pollen season (GPs group) and out of the pollen season (GPos group), and on 14 patients monoallergic to house dust mite (HDM) from May to September (HDM group). Main outcome measures were changes in concentrations of IL‐10 in the supernatant after a 4‐week treatment with montelukast. Measurements of asthma severity score, forced expiratory volume in 1 s (FEV1) and peripheral blood eosinophil counts were the secondary end‐points.Results
Montelukast resulted in a within‐group significant increase in IL‐10 concentration in the supernatant in the GPs (54.0 vs. 125.5 pg/mL) and in the HDM (51.2 vs. 77.1 pg/mL) group. Montelukast had no effect on changes of IL‐10 concentration in the supernatant from peripheral blood mononuclear cell (PBMC) culture after non‐sensitizing allergen stimulation. Montelukast significantly improved asthma control and FEV1, and significantly decreased eosinophil blood count in the GPs and in the HDM group after a 4‐week treatment. Montelukast did not lead to changes of all measured parameters within the GPos group.Conclusion
Montelukast increased IL‐10 concentration in supernatants from sensitizing allergen‐stimulated PBMC culture obtained from children with asthma monoallergic to grass pollen during the pollen season, and from children with asthma monoallergic to HDM.