| 2701. |
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| 2702. |
- Nielsen, Lene Kongsgaard, et al.
(författare)
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Health-related quality of life in transplant ineligible newly diagnosed multiple myeloma patients treated with either thalidomide or lenalidomide-based regimen until progression : A prospective, open-label, multicenter, randomized, phase 3 study
- 2020
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 105:6, s. 1650-1659
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Tidskriftsartikel (refereegranskat)abstract
- Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after three and nine induction cycles and six and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in HRQoL reporting. Patients reported clinically relevant improvement in global quality of life (QoL), future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size. In general, improvement occurred after 6-12 months of maintenance only and was independent of the World Health Organisation performance at baseline. Patients treated with MPR-R reported clinically relevant worsening of diarrhea, and patients treated with MPT-T reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least three months reported clinically meaningful improvement in global QoL and role functioning at six months, remaining stable thereafter. There were no clinically meaningful deteriorations, but patients on thalidomide reported clinically relevant worsening in neuropathy. In general, HRQoL improves both during induction and maintenance therapy with immunomodulatory drugs. The side effect profile of treatment did not negatively affect global QoL, but it was, however, clinically relevant for the patients.
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| 2703. |
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| 2704. |
- Nijdam, A., et al.
(författare)
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How to achieve full prophylaxis in young boys with severe haemophilia A: different regimens and their effect on early bleeding and venous access
- 2015
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Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 21:4, s. 444-450
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Tidskriftsartikel (refereegranskat)abstract
- To facilitate early prophylaxis, step-up regimens starting prophylaxis with infusions 1xweek(-1) were introduced. Choice of initial regimen may affect outcome. This study aims to classify initial prophylactic regimens and compare them on short-term outcome. From the European Paediatric Network for Haemophilia Management' (PedNet) registry, patients with severe haemophilia A without inhibitors, born 2000-2012, receiving prophylaxis were included. Treatment centres were classified according to the initial frequency of prophylactic infusions and the age at reaching infusions >= 3 x week(-1). Bleeding, and central venous access device (CVAD) use were compared at age 4 years. In 21 centres with 363 patients, three regimens were identified: (i) start prophylaxis with >= 3 x week(-1) infusions before age three (full: 19% of centres, 18% of patients); (ii) start 1-2 x week(-1), increasing frequency as soon as possible (asap), reaching >= 3 x week(-1) before age three (43% of centres, 36% of patients); (iii) start 1-2 x week(-1), increasing frequency according to bleeding (phenotype), reaching >= 3 x week(-1) after age three (38% of centres, 46% of patients). Prophylaxis was started at median 1.2 years on the full and asap regimen vs 1.8 years on the phenotype regimen. Complete prevention of joint bleeds was most effective on the full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of using most CVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis regimens identified had different effects on early bleeding and CVAD use. This classification provides the first step towards establishing the optimum prophylactic regimen.
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| 2705. |
- Nikiforow, Sarah, et al.
(författare)
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Upper gastrointestinal acute graft-versus-host disease adds minimal prognostic value in isolation or with other graft-versus-host disease symptoms as currently diagnosed and treated.
- 2018
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 103:10, s. 1708-1719
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Tidskriftsartikel (refereegranskat)abstract
- Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess the prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graft-versus-host disease manifestations. 8567 adult recipients of myeloablative allogeneic hematopoietic stem cell transplant receiving T-cell replete grafts for acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome between 2000 and 2012 were analyzed. 51% of transplants were from unrelated donors. Reported upper gastrointestinal acute graft-versus-host disease incidence was 12.1%; 2.7% of recipients had isolated upper gastrointestinal acute graft-versus-host disease, of whom 95% received systemic steroids. Patients with isolated upper gastrointestinal involvement had similar survival, disease-free survival, transplant-related mortality, and relapse as patients with Grades 0, I, or II acute graft-versus-host disease. Unrelated donor recipients with isolated upper gastrointestinal acute graft-versus-host disease had less subsequent chronic graft-versus-host disease than those with Grades I or II disease (P=0.016 and P=0.0004, respectively). Upper gastrointestinal involvement added no significant prognostic information when present in addition to other manifestations of Grades I or II acute graft-versus-host disease. If upper gastrointestinal symptoms were reclassified as Grade 0 or I, 425 of 2083 patients (20.4%) with Grade II disease would be downgraded, potentially impacting the interpretation of clinical trial outcomes. Defining upper gastrointestinal acute graft-versus-host disease as a Grade II entity, as it is currently diagnosed and treated, is not strongly supported by this analysis. The general approach to diagnosis, treatment and grading of upper gastrointestinal symptoms and their impact on subsequent acute graft-versus-host disease therapy warrants reevaluation.
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| 2706. |
- Nilsson, Anders K., 1982, et al.
(författare)
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The proteome signature of cord blood plasma with high hematopoietic stem and progenitor cell count
- 2022
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Ingår i: Stem Cell Research. - : Elsevier BV. - 1873-5061. ; 61
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem and progenitor cells (HSPC) from umbilical cord blood (UCB) are used for transplantation to treat blood disorders. Methods to estimate the HSPC count in umbilical cord blood, and thereby identify high-value blood units, are time-consuming and costly. Recent studies indicate that the UCB plasma protein composition relates to the HSPC count. We compared the plasma proteome of UCB with high vs low HSPC cell count (> 115 x 10(6) vs < 51 x 10(6) CD34(+) cells l(-1)) by using a combination of global untargeted MS quantitative proteomics and targeted proximity extension assay (PEA) proteomics. For the MS platform, 96 proteins differed significantly between the CD34(+) groups, and out of these, 44 proteins showed more than a two-fold difference. Seven pathways were enriched in high CD34(+) samples, including pathways relating to platelets, coagulation, and lipid transport. For the PEA platform, 61 proteins were differentially abundant, and among these 7 proteins showed more than a two-fold difference between groups. In the PEA data, a high CD34(+) cell count was associated with a protein hub with functions in platelet degranulation. We conclude that the HSPC count is related to the UCB plasma proteome, but that further studies are needed to discern if these findings reflect causal relationships.
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| 2707. |
- Nilsson, Alexandra Rundberg, et al.
(författare)
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IRF1 regulates self-renewal and stress-responsiveness to support hematopoietic stem cell maintenance
- 2023
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Inflammatory mediators induce emergency myelopoiesis and cycling of adult hematopoietic stem cells (HSCs) through incompletely understood mechanisms. To suppress the unwanted effects of inflammation and preserve its beneficial outcomes, the mechanisms by which inflammation affects hematopoiesis need to be fully elucidated. Rather than focusing on specific inflammatory stimuli, we here investigated the role of transcription factor Interferon (IFN) regulatory factor 1 (IRF1), which receives input from several inflammatory signaling pathways. We identify IRF1 as a master HSC regulator. IRF1 loss impairs HSC self-renewal, increases stress-induced cell cycle activation, and confers apoptosis resistance. Transcriptomic analysis revealed an aged, inflammatory signature devoid of IFN signaling with reduced megakaryocytic/erythroid priming and antigen presentation in IRF1-deficient HSCs. Finally, we conducted IRF1-based AML patient stratification to identify groups with distinct proliferative, survival and differentiation features, overlapping with our murine HSC results. Our findings position IRF1 as a pivotal regulator of HSC preservation and stress-induced responses.Competing Interest StatementThe authors have declared no competing interest.
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| 2708. |
- Nilsson, Björn, et al.
(författare)
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Cross-platform classification in microarray-based leukemia diagnostics
- 2006
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Ingår i: Haematologica. - 1592-8721 .- 0390-6078. ; 91:6, s. 821-824
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Tidskriftsartikel (refereegranskat)abstract
- Gene expression profiling is a powerful technique for classifying hematologic malignancies. Its clinical use is, however, currently hindered by the need to collect large sets of expression profiles at each diagnostic facility. To overcome this limitation, we introduced cross-platform classification, allowing classifier construction using pre-existing microarray datasets. As proof-of-principle, we performed cross-platform classification of acute myeloid leukemia and childhood acute lymphoblastic leukemia using expression data from four different facilities. We show that cross-platform classification of these disorders is achievable, and, strikingly, that the diagnostic accuracy can be retained. We conclude that cross-platform classification constitutes an effective and convenient way to implement microarray diagnostics.
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| 2709. |
- Nilsson, Caroline, et al.
(författare)
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Monitoring fondaparinux with the Sonoclot
- 2007
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Ingår i: Blood Coagulation and Fibrinolysis. - 1473-5733. ; 18:7, s. 619-622
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Tidskriftsartikel (refereegranskat)abstract
- Fondaparinux is a new anticoagulant that interacts with antithrombin III and activated coagulation factor X resulting in an inhibition of the coagulation system. It has been successful in doses of 2.5 mg for thromboprophylaxis as well as in higher therapeutic doses of 5-7.5 mg. No optimal method for monitoring the effects of fondaparinux has been proposed. The aim of the present study was to investigate whether a viscoelastic coagulation analyzer, the Sonoclot (Sienco, Denver, Colorado, USA), could be used for in-vitro monitoring of fondaparinux. Different concentrations of fondaparinux were added in vitro to whole blood taken from eight volunteers. The blood samples mixed with the various amounts of fondaparinux were analyzed using the Sonoclot. The whole-blood activated partial thromboplastin time with the Hemochron Jr (ITC, Edison, New Jersey, USA) was used as the reference coagulation analysis. All analyses were started expeditiously, within 30s from sampling, and were performed at 37 degrees C. The values of the Sonoclot parameter clot rate, which measures the rate of fibrin formation, fibrin polymerization and platelet-fibrin interactions, were significantly correlated to increasing concentrations of fondaparinux (R= -0.90). The Sonoclot parameters of activated coagulation time, time to peak and clot retraction had weaker, butstill significant, correlations to fondaparinux concentrations. At prophylactic doses (0.38 mu g/ml blood) the clot rate decreased 15% compared with the initial unanticoagulated value, whereas at therapeutic doses (1.53 mu blood) there was a 27% decrease. In conclusion, the Sonoclot parameter clot rate could be of clinical value to individualize the fonclaparinux dosage, especially the higher, therapeutic, dosages. Blood Coagul Fibrinolysis 18:619-622 (c) 2007 Lippincott Williams & Wilkins.
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| 2710. |
- Nilsson, Christer, et al.
(författare)
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Secondary Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation in a Population-Based Setting
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 25:9, s. 1770-1778
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Tidskriftsartikel (refereegranskat)abstract
- Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML.
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