| 1. |
- Benson, Gary, et al.
(författare)
-
Immune tolerance induction in patients with severe hemophilia with inhibitors: expert panel views and recommendations for clinical practice.
- 2012
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:5, s. 371-379
-
Tidskriftsartikel (refereegranskat)abstract
- For hemophilia patients with inhibitors, immune tolerance induction (ITI) may help to restore clinical response to Factor (F) VIII or FIX concentrates. Several ITI regimens and protocols exist; however, despite 30 yr of progressive investigation, the ITI evidence base relies mainly on observational data. Expert opinion, experience, and interpretation of the available evidence are therefore valuable to support clinical decision-making. At the Sixth Zürich Haemophilia Forum an expert panel considered recent data and consensus to distill key practice points relating to ITI. The panel supported current recommendations that, where feasible, ITI should be offered early to children and adults (ideally ≤5 yr of inhibitor detection) when inhibitor titers are <10 Bethesda Units, and should be stopped when successful tolerance is achieved. For hemophilia A inhibitor patients, ITI can be founded on recombinant FVIII at high doses. The panel considered that patients with a high bleeding frequency should be offered additional prophylaxis with a bypassing agent. For hemophilia B patients, there may be a benefit to genetic testing to indicate the risk for inhibitors. ITI is often less effective and associated with a greater risk of side effects in these patients. For high-titer inhibitor (≥5 Bethesda Units) hemophilia B patients, the panel advised that bypassing agents could be offered on demand in addition to ITI. Within future ITI regimens there may be a role for additional immunosuppressant therapies. Participants agreed that research is needed to find alternatives to ITI therapy that offer durable and sustained effects and reduced rates of complications. © 2012 John Wiley & Sons A/S.
|
|
| 2. |
- Blank Savukinas, Ulrika, et al.
(författare)
-
Angptl4 maintains in vivo repopulation capacity of CD34(+) human cord blood cells.
- 2012
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 89:3, s. 198-205
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Methods to expand hematopoietic stem cells (HSCs) ex vivo encompass an attractive approach that would substantially broaden the clinical applicability of HSCs derived from cord blood. Recently, members of the Angiopoietin-like (Angptl) family of growth factors were shown to expand both murine and human HSCs. Specifically, Angptl5 has been implicated in the expansion of human NOD-SCID-repopulating cells (SRCs) ex vivo. Here, we sought to evaluate the potential of additional Angptls to expand human SRCs from cord blood. Additionally, the purpose of this study was to evaluate the reproducibility of Angptl-mediated expansion of SRCs across independent experiments. METHODS: Human CD34(+) cells from cord blood were cultured in vitro for eleven or eight days in the presence or absence of Angptls. The reconstitution capacity of expanded cells was subsequently measured in vivo by transplantation into NOD-SCID or NSG mice, and compared to that of uncultured cells. RESULTS: We report here that Angptl4 functions to maintain SRC-activity of CD34(+) CB-derived cells ex vivo as assayed in NOD-SCID and NSG mice. However, all Angptls tested, including Angptl1, 4, and 5, were associated with variation between experiments. CONCLUSION: Our findings indicate that Angptl4 and Angptl5 can lead to increased engraftment capacity of SRCs, but more frequently these factors are associated with maintenance of SRC-activity during ex vivo culture. Thus, Angptl-mediated expansion of SRCs ex vivo is associated with more inter-experimental variation than previously thought. We conclude that Angptls would be useful in instances where there is a need to maintain HSCs ex vivo, such as during transduction for gene therapy applications.
|
|
| 3. |
- Khawaji, Mohammed, et al.
(författare)
-
Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life.
- 2012
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:4, s. 329-335
-
Tidskriftsartikel (refereegranskat)abstract
- Background: In the 1950s, Sweden initiated prophylaxis as a lifelong treatment for haemophilia. It was the first country to do so. Objective: To describe and evaluate dosing and outcome of prophylactic treatment in a large cohort of adult people with severe haemophilia who have been using prophylaxis most of their lives. Methods: Eighty-one patients born between 1932 and1992 were divided into two groups (Group A started prophylaxis at the age of ≤ 3 years; Group B at three or more years of age) and evaluated retrospectively. Outcome was evaluated using the Hemophilia Joint Health Score (HJHS) and SF-36, a measure of quality of life. Results: The median number of joint bleeds per year was 0 in both study groups; however, the annual number of joint bleeds during the final three years of observation was higher in group B than group A (p< 0.006). Twenty-five of 30 patients in group A and 27/51 patients in group B had no joint bleeds in that period. Group A had significantly better joint outcomes than group B. Patients in group A experienced better physical and social health than those in group B. Conclusions: This follow-up has provided for the first time more extensive and detailed information regarding the practice of prophylactic treatment in a large cohort of adults with severe haemophilia. The present study confirms, that early start of prophylaxis and continuing throughout the lifespan has been successful in virtually eliminating joint bleeds, preserving a close to normal joint status, and keeping patients healthy and able to live normal lives. © 2012 John Wiley & Sons A/S.
|
|
| 4. |
- Larsson, Nina, et al.
(författare)
-
Myeloid malignancies with acquired trisomy 21 as the sole cytogenetic change are clinically highly variable and display a heterogeneous pattern of copy number alterations and mutations(a).
- 2012
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:2, s. 136-143
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Acquired trisomy 21 is one of the most common numerical abnormalities in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), and MDS/MPN; however, little is known about its pathogenic impact, accompanying submicroscopic changes, and its relation to other clinical features. Furthermore, previous studies addressing this issue have mainly focused on cases in which +21 was part of a complex karyotype. Methods: We ascertained the incidence of +21, both as a sole change (T21s) and irrespective of additional changes (T21all), in relation to disease type, morphologic subgroup, gender, and age in all published AML, MDS, MPN, and MDS/MPN cases. Furthermore, single nucleotide polymorphism (SNP) array analysis was performed on 11 myeloid malignancies with T21s, followed by mutation analysis of the FGFR1, FLT3, GATA1, JAK2, KIT, NPM1, NRAS, RUNX1, and TET2 genes. Results: The frequencies of T21s and/or T21all varied significantly among the AML, MDS, MPN and MDS/MPN cases, among the AML and MPN subtypes, and in relation to the age of the AML, MDS, and MPN patients. In the 11 cases analyzed by SNP array, a total of nine genomic imbalances, comprising seven deletions and two duplications, were identified in six cases; none of the alterations were recurrent. Partial uniparental disomies (UPDs) were found in five cases; two recurrent UPDs were identified, namely UPD4q and UPD7q. Mutations in NPM1, RUNX1, and TET2 were detected in five cases, three of which harboured a pathogenic RUNX1 mutation. The TET2 mutation was found in one of the cases with UPD4q. Conclusions: The results show that trisomy 21-positive myeloid malignancies are clinically highly variable and that they display a heterogeneous pattern of copy number alterations and mutations.
|
|
| 5. |
- Miesbach, Wolfgang, et al.
(författare)
-
When von Willebrand disease comes into age - A matter of change?
- 2011
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 86, s. 496-501
-
Tidskriftsartikel (refereegranskat)abstract
- The population of elderly patients with von Willebrand Disease (VWD) is growing due to the improvement of medical care. The increase of co-morbidities and their treatment as well as standard preventive measures like anti-platelet or anticoagulation therapy constitute a challenge in the overall treatment of patients with coagulation disorders. Due to the lack of literature on older VWD patients, we discuss different aspects related to ageing in those patients. Plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII), bleeding symptoms, treatment requirements and co-morbidities are possibly changing with age. Development of an evidence-based approach to the management of ageing VWD patients is therefore necessary.
|
|
| 6. |
- Nilsson-Ehle, Herman, et al.
(författare)
-
Quality of life, physical function and MRI T2*in elderly low-risk MDS patients treated to a haemoglobin level of andgt;= 120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions
- 2011
-
Ingår i: European Journal of Haematology. - : John Wiley and Sons. - 0902-4441 .- 1600-0609. ; 87:3, s. 244-252
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Anaemia in low-risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin +/- granulocyte colony-stimulating factor (G-CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of andgt; 120 g /L. Methods: Thirty-six elderly patients with low-and intermediate-1 risk MDS received darbepoetin (DA) 300 mu g/wk, with the addition of G-CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty-seven patients completed the study. Response rate to DA +/- G-CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb andgt; 120 g /L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.
|
|
| 7. |
- Riihijarvi, Sari, et al.
(författare)
-
Male gender is an adverse prognostic factor in B-cell lymphoma patients treated with immunochemotherapy
- 2011
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 86:2, s. 124-128
-
Tidskriftsartikel (refereegranskat)abstract
- Male gender is an adverse prognostic factor in Hodgkin's lymphoma, but no such association has yet been established in non-Hodgkin lymphomas. Here, we have evaluated whether gender has prognostic impact on the survival of patients with B-cell non-Hodgkin lymphoma in the postrituximab era of lymphoma therapies. The study populations consisted of 217 diffuse large B-cell lymphoma (DLBCL) and 110 follicular lymphoma (FL) patients treated with immunochemotherapy. Hundred and sixty chemotherapy-treated DLBCL patients served as a control group. According to Kaplan-Meier analyses, female patients had a significantly better progression-free survival than men both in DLBCL (4 yr PFS 75% vs. 60%; P = 0.013) and in FL (4 yr PFS 68% vs. 52%, P = 0.036) patients treated with immunochemotherapy. In chemotherapy-treated DLBCL patients, no difference in survival between the genders was found. The results support the idea that women seem to respond better to rituximab.
|
|
| 8. |
- Thörn, Ingrid, et al.
(författare)
-
Applicability of IG/TCR gene rearrangements as targets for minimal residual disease assessment in a population-based cohort of Swedish childhood acute lymphoblastic leukaemia diagnosed 2002-2006.
- 2010
-
Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 84:2, s. 117-27
-
Tidskriftsartikel (refereegranskat)abstract
- Minimal residual disease (MRD) detection during the early treatment phase has become an important stratification parameter in many childhood acute lymphoblastic leukaemia (ALL) treatment protocols. Here, we aimed to address the applicability of rearranged antigen-receptor genes as potential MRD markers using real-time quantitative polymerase chain reaction (RQ-PCR) in a Swedish population-based cohort. From 334 childhood ALL cases diagnosed during 2002-2006, we analysed 279 diagnostic samples (84%) by screening for rearranged immunoglobulin (IG) and T-cell receptor (TCR) genes. Allele-specific oligonucleotides were designed, and the sensitivity and quantitative level was determined for each target. Overall, clonal IG/TCR rearrangements were detected in 97% (236/244) of B-cell precursor ALL (BCP ALL) and 94% (33/35) of T-ALL. A sensitive RQ-PCR analysis (< or = 10(-4)) was obtained in 89% (216/244) of BCP ALL and in 74% (26/35) of T-ALL, whereas two sensitive targets were only available in 47% (115/244) of BCP ALL and 29% (10/35) of T-ALL cases. With the stratification threshold of > or = 10(-3), which is applied in the current Nordic treatment protocol (NOPHO-ALL 2008) for the identification of high-risk patients, 93% of BCP ALL and 86% of T-ALL reached this quantitative range by at least one target gene. Taken together, this national retrospective study demonstrates that an IG/TCR target for MRD monitoring can be identified in the majority of childhood ALL cases, whereas identification of a second sensitive target gene needs to be improved.
|
|
| 9. |
- Willander, Kerstin, et al.
(författare)
-
MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemia
- 2010
-
Ingår i: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 85:3, s. 251-256
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective: In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients: A total of 210 patients with B-CLL were followed for up to 19 yr. Results: The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. Conclusion: In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients.
|
|
| 10. |
|
|
