| 1. |
- Berntorp, Erik, et al.
(author)
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A systematic overview of the first pasteurised VWF/FVIII medicinal product, Haemate P/ Humate -P: history and clinical performance.
- 2008
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In: European Journal of Haematology. Supplementum. - : Wiley. - 0902-4506 .- 0902-4441 .- 1600-0609. ; 80:s70, s. 3-35
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Research review (peer-reviewed)abstract
- Patients with von Willebrand disease (VWD) and haemophilia A (HA) lack, to varying degrees, the von Willebrand factor (VWF) and coagulation factor VIII (FVIII) that are critical for normal haemostasis. These conditions in turn make patients prone to uncontrolled bleeding. Historically, patients with severe forms of VWD or HA were crippled before adulthood and their life expectancy was significantly reduced. Over the past decades, specific coagulation factor replacement therapies including Haemate P, have been developed to help patients achieve and maintain normal haemostasis. Haemate P is a human, plasma-derived VWF/FVIII medicinal product, which was first licensed in Germany in 1981 for the treatment of HA-associated bleeding. It has since then come to be accepted as the gold standard for both the treatment and prophylaxis of bleeding in VWD, especially in cases where desmopressin [1-deamino-8-D-arginine vasopressin (DDAVP)] has been ineffective. Haemate P was the first effectively virus-inactivated (pasteurisation: 60 degrees C for 10 h in aqueous solution) FVIII product, whereby the risk of potentially threatening infective complications of plasma-derived products was reduced. Haemate P was also shown to have a VWF multimer profile remarkably close to that of normal plasma. This bibliographic review presents previously unpublished clinical data of Haemate P, based upon internal clinical study reports of the proprietor, CSL Behring, in addition to data already presented in other publications. The data demonstrate a predictable and well-characterised pharmacokinetic profile, and a proven record of short- and long-term safety, while effectively correcting the haemostatic defects in VWD and HA. Recently available data have also shown Haemate P to be of haemostatic value in exceptional clinical circumstances including surgical interventions. By virtue of its plasma-derived combination of VWF and FVIII, in addition to its high VWF:FVIII content ratio (2.4:1), Haemate P is also associated with successful immune tolerance induction in those patients developing inhibitor antibodies. Although the theoretical risk of thromboembolic complications does exist while receiving Haemate P, as it does with any FVIII replacement therapy, the incidence of such complications has remained notably low. Given the robust data that have accumulated for the use of Haemate P, dosing recommendations are also described in this review; the recommendations are tailored to patient-specific contexts including baseline VWF and FVIII levels in plasma and the type of surgical intervention being undertaken. A wide variety of studies have also provided data on paediatric and geriatric populations, all of which have suggested that Haemate P can be safely and effectively used in a wide variety of clinical circumstances.
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| 2. |
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| 3. |
- Benson, Gary, et al.
(author)
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Immune tolerance induction in patients with severe hemophilia with inhibitors: expert panel views and recommendations for clinical practice.
- 2012
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:5, s. 371-379
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Journal article (peer-reviewed)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.
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| 4. |
- Lundin, Catarina, et al.
(author)
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B-cell precursor t(8;14)(q11;q32)-positive acute lymphoblastic leukemia in children is strongly associated with Down syndrome or with a concomitant Philadelphia chromosome.
- 2009
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 82:1, s. 46-53
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Journal article (peer-reviewed)abstract
- We review the clinical and cytogenetic features of 44 acute lymphoblastic leukemias (ALLs) with t(8;14)(q11;q32), including three from our department and 41 ascertained in the literature, focusing on age and gender distribution, peripheral blood values, immunophenotypic data, survival and additional chromosomal changes. Most patients are children or young adults, with a median age of 10 yr for children and 28 for adults. There is a male preponderance, particularly in patients with Down syndrome (DS) or in children with concomitant t(9;22)(q34;q11). The median blood values are hemoglobin 72 g/L, platelets 17 x 10(9)/L and white blood cell count 9 x 10(9)/L, with hyperleukocytosis >50 x 10(9)/L having been reported in only approximately 10%. All reported cases have had a B-cell precursor immunophenotype, typically characterized by CD10+, CD19+, CD20+/-, CD22+, CD24+, CD34+, CD45dim/-, CD66c+/- and CD123+. At the time of reporting, 75% of the patients have been alive. The t(8;14) is the sole acquired change in 30%. The most common additional aberrations are t(9;22)(q34;q11), der(14)t(8;14), +21, +X and +14, the presence of which does not seem to confer a prognostic impact. A substantial proportion of the patients have DS (27%) or t(9;22) (16%). All patients with both t(8;14) and t(9;22) have been children without DS; the frequency of t(9;22) in that cohort is 30%. As t(9;22), or its molecular genetic correlate, may escape detection by conventional banding analysis we would strongly suggest that this aberration is actively looked for in pediatric ALL with t(8;14).
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| 5. |
- Olsson, I, et al.
(author)
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Cell differentiation in acute myeloid leukemia
- 1996
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 57:1, s. 1-16
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Research review (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is characterized by a differentiation block leading to accumulation of immature cells. Chromosomal translocations in AML affect transcription factors that are involved in regulation of myeloid differentiation. Aberrant expression of these factors interferes with differentiation events and has a role in the pathogenesis of AML through superactivation or (dominant negative) repression of genes regulating proliferation and differentiation or by interference with assembly of the transcription complex for these genes. The maturation arrest can be reversed by certain agents as judged by results from investigations of myeloid leukemic cell lines and from treatment of acute promyelocytic leukemia (APL) patients with all-trans retinoic acid. Inactivation of the p53 and retinoblastoma (Rb) tumor suppressor genes is also associated with the pathogenesis of leukemia through effects on the cell cycle, and manipulation of these genes can affect differentiation of AML cells. With differentiation therapy, when successful as in APL, the leukemic cell mass is reduced to allow restoration of normal hematopoiesis and clinical remission, but the disease is not cured. However, initial reduction of the cell mass by maturation can increase the probability for cure with chemotherapy. Overexpression of suppressor genes may increase the probability for differentiation. Most probably, particular molecular defects of subgroups of AML have to be explored to find optimal strategies for treatment including both blocking the cell cycle, promoting terminal differentiation, and inducing apoptosis as well as strengthening the immune response.
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| 6. |
- Gullberg, U, et al.
(author)
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Biosynthesis, processing and sorting of neutrophil proteins : insight into neutrophil granule development
- 1997
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 58:3, s. 137-153
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Journal article (peer-reviewed)abstract
- Neutrophil granulocytes are specialized phagocytic cells that carry a collection of granules for regulated secretion, each with distinct constituents. The granules can be classified as azurophil (primary), developed first, followed in time by specific (secondary) granules gelatinase granules, and secretory vesicles. Stage- and tissue-specific transcription factors govern the successive expression of genes for granule proteins to allow storage of the gene products in these organelle categories whose packaging is separated in time. Many of the granule proteins, in particular those of the heterogeneous lysosome-like azurophil granules, are subject to extensive post-translational proteolytic processing into mature proteins, most commonly as a post-sorting event. A selective aggregation of proteins destined for storage in granules, as discussed in this review, would facilitate their retention and eliminate a need for distinct sorting motifs on each granule protein. Aggregation of granule proteins, that are often cationic, would be assisted by the anionic serglycin proteoglycans present in neutrophils. The antibacterial granule proteins can serve as models for antibiotics and some of them possess a potentially useful therapeutic ability to bind and neutralize endotoxin. Because aberrant expression of transcription factors regulating the synthesis of granule proteins is often found in leukemia, the clarification of mechanisms regulating the timed expression of granule proteins will shed light on the maturation block in myeloid leukemias.
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| 7. |
- Amini, Rose-Marie, et al.
(author)
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A population-based study of the outcome for patients with first relapse of Hodgkin's lymphoma
- 2002
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 68:4, s. 225-232
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Journal article (peer-reviewed)abstract
- Background: Our aims were to evaluate the response to salvage treatment in relation to initial treatment and to evaluate prognostic factors at the time of relapse in an unselected population of relapsing patients with Hodgkin's lymphoma (HL). Patients and methods: In total, 124 patients younger than 60 yr of age with initial diagnosis of HL in Sweden relapsed between 1985 and 1995. Results: Fifty-eight patients relapsed after initial treatment with radiotherapy (RT) only, 62 after combination chemotherapy (CT), of whom 30 had received additional involved-field RT, and four after a short course of CT followed by extended-field RT. For 37 patients among the 58 relapsers after initial RT treated according to the recommendations of the National guidelines, the 5-yr Hodgkin-specific survival (HLS) was 85%, overall survival (OS) 73% and event-free survival (EFS) 62%, which is not inferior to survival in patients with primarily advanced stages. It was poorer in the 21 patients who initially had received RT only, even though they had been recommended for more extensive treatment. For patients initially treated with a full course (6-8 cycles) of CT the 5-yr HLS was 60%, OS 58% and EFS 22%. Bulky disease and age at diagnosis strongly affected survival in a multivariate analysis. Conclusions: Patients initially treated with RT who relapse have a favourable outcome, provided they have been treated according to the recommendations of the guidelines at the time of diagnosis. Initially bulky disease and, as a consequence, additional RT as part of the initial treatment negatively affect survival at relapse in patients initially treated with a full course of CT.
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| 8. |
- Andersen, NS, et al.
(author)
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Primary treatment with autologous stem cell transplantation in mantle cell lymphoma: outcome related to remission pretransplant
- 2003
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 71:2, s. 73-80
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Journal article (peer-reviewed)abstract
- Objective: The aim of the first Nordic mantle cell lymphoma (MCL) protocol was to study the clinical significance of an augmented CHOP induction chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) and to examine the prognostic significance of stem cell contamination rates in newly diagnosed patients with MCL. Patients and methods: Forty-one newly diagnosed patients below 66 yr were enrolled and given three series of an augmented CHOP regimen. Responders underwent stem cell mobilization with a fourth course of CHOP, stem cell harvest and ASCT. Stem cell purging was optional in the protocol and followed the routine of each participating centre. The number of tumour cells in the reinfused autografts was estimated by flow cytometry or quantitative PCR. Results: Induction therapy led to complete remission (CR) in 11 of 41 patients (27%), partial remission (PR) in 20 of 41 patients (49%) and no response in nine patients (22%), whereas one patient was not evaluable. Twenty-seven of the 31 responders underwent ASCT and 24 achieved or maintained a CR. The overall and failure-free 4-yr survival on intention-to-treat basis were 51% and 15%, respectively. Among the transplanted patients, a significantly increased failure-free (P < 0.03) and overall survival (P = 0.03) was noted among patients transplanted in CR compared with PR, respectively. By contrast, reinfusion of highly variable numbers of tumour cells with the autografts (range 0.71-80 x 10(6) tumour cells), did not affect outcome. Conclusion: In MCL, an important strategy to improve the outcome will be to intensify the induction chemotherapy.
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| 9. |
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| 10. |
- Andreasson, B, et al.
(author)
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Management of patients with polycythaemia vera: results of a survey among Swedish haematologists
- 2005
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 74:6, s. 489-495
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Journal article (peer-reviewed)abstract
- The prevailing attitudes regarding diagnostic and therapeutic procedures in patients with polycythaemia vera (PV) among Swedish haematologists were surveyed by way of a mailed questionnaire in August 2002. Among diagnostic procedures frequent use is reported for arterial O-2 saturation, spleen size determination, bone marrow histology, serum erythropoietin, serum cobalamins and leukocyte alkaline phosphatase score, while direct determination of the red blood cell mass is used infrequently (seldom or never by 82%). Among therapeutic modalities hydroxyurea and phlebotomy alone were most frequently used. The P-32 therapy was used at least sometimes by 57% of the physicians, and more widely in the university clinics. Anagrelide and alfa-interferon was used in a minority of patients only. The use of prophylactic acetylsalicylic acid was very variable. The majority of the physicians had an aim for their phlebotomy treatment at a level of 0.45 or less, but 21% used a level of 0.46-0.49 and 8% a level of 0.55-0.60 (in younger patients). The platelet level, at which myelosuppressive therapy was initiated, also varied, from 400 x 10(9)/L to > 1500 x 10(9)/L. It can be concluded that in practical clinical work in Sweden the diagnosis of PV is established by frequent use of serum erythropoietin, bone marrow examination and spleen size determination. The use of different therapeutic modalities is very variable. Many physicians carry out their phlebotomy treatment with less intensity compared with national and international recommendations.
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| 11. |
- Andreasson, Patrik, et al.
(author)
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Cytogenetic and FISH studies of a single center consecutive series of 152 childhood acute lymphoblastic leukemias
- 2000
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 65:1, s. 40-51
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Journal article (peer-reviewed)abstract
- Between 1977 and 1996, cytogenetic investigations were performed on 182 childhood (< or = 16 yr) acute lymphoblastic leukemias (ALL), constituting 94% (182 of 194) of all ALL patients diagnosed and treated at the Departments of Pediatrics, Lund and Malmo University Hospitals, Sweden, during these two decades. The cytogenetic analyses were successful in 152 cases (84%). The failure rate was higher for the ALL investigated before 1987 (30% vs. 4%, p < 0.0001), and also the incidence of cytogenetically normal cases was higher during 1977-86 (43% vs. 25%, p < 0.05). Clonal chromosomal abnormalities were found in 103 (68%) ALL. Structural rearrangements were detected, by chromosome banding alone, in 76 cases (50%). Fluorescence in situ hybridization (FISH) was used to identify cases with t(12;21), 11q23 rearrangements, and 9p deletions, using probes for ETV6/CBFA2, MLL, and CDKN2A/B, in 72 cases from which cells in fixative and/or unstained metaphase preparations were available. In total, the most common structural rearrangements were del(9p) (17%), t(12;21) (15%), del(6q) (8%), and MLL rearrangements (4%). Six (32%) of nineteen cytogenetically normal ALL analyzed by FISH harbored cryptic abnormalities; three displayed t(12;21) and four had del(9p), one of which also carried a t(12;21). Five (45%) of the t(12;21)-positive ALL showed +der(21)t(12;21) or ider(21)(q10)t(12;21), resulting in the formation of double fusion genes. Among the more rare aberrations, eight structural rearrangements were identified as novel recurrent ALL-associated abnormalities, and nine cases harbored rearrangements previously not reported. Sixteen cases displayed karyotypically unrelated clones at different investigations. Seven ALL (5%) showed simple chromosomal changes, unrelated to the aberrations detected at diagnosis, during morphologic and clinical remission, and in all but one instance the patients remained in remission, with the abnormal clone disappearing in subsequent investigations. This indicates that the emergence of novel clonal chromosomal aberrations during remission in childhood ALL is rather common and does not by necessity predict a forthcoming relapse.
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| 12. |
- Blank Savukinas, Ulrika, et al.
(author)
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Angptl4 maintains in vivo repopulation capacity of CD34(+) human cord blood cells.
- 2012
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 89:3, s. 198-205
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Journal article (peer-reviewed)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.
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| 13. |
- Brandt, Lars, et al.
(author)
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Relation between occupational exposure to organic solvents and chromosome aberrations in non‐Hodgkin's lymphoma
- 1989
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 42:3, s. 298-302
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Journal article (peer-reviewed)abstract
- Chromosome analysis of lymphoma cells was performed in 54 untreated patients with non‐Hodgkin's lymphoma (NHL). 10 patients had a history of daily occupational handling of organic solvents for at least 1 year (exposed group) and 44 patients had never (or only for shorter periods) worked with solvents (unexposed group). There were no differences between exposed and unexposed patients regarding age, clinical stage or histologic malignancy grade. The patients were assigned to three categories: Patients with 0–4, 5–9, or ≥ 10 cytogenetic events producing clonal aberrations of the lymphoma cells. The proportions of exposed patients in these categories were 2/26 (8%), 5/20 (25%) and 3/8 (38%); respectively, i.e. with increasing numbers of events there was an increasing probability of previous exposure to solvents (p = 0.035; trend analysis). 5 of 7 exposed patients (71%) with intermediate or high‐grade lymphomas displayed translocations involving the band 14q32. Such 14q+ markers were found in only 5 out of 28 unexposed patients (18%) with lymphomas of comparable malignancy grade (p = 0.01). Among unexposed patients with intermediate or high‐grade lymphoma the most common clonal aberration was 6q‐ which occurred in 10 out of 28 patients (36%). This abnormality was not observed in the exposed patients with lymphomas of corresponding malignancy grades (p = 0.08). It thus appears that the number of clonal chromosome aberrations is especially large in NHL patients with a history of occupational exposure to organic solvents. Moreover, such exposure may be associated with characteristic cytogenetic changes in the lymphoma cells.
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| 14. |
- Brandt, Lars, et al.
(author)
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Survival following combination chemotherapy in advanced high grade non‐Hodgkin's lymphomas : Relation to proliferative activity of the lymphoma cells
- 1987
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 38:5, s. 437-441
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Journal article (peer-reviewed)abstract
- In 18 untreated adult patients (median age 62.5 yr) with advanced non‐Hodgkin's lymphoma of unfavourable histology, thymidine labelling indices (LIs) of the lymphoma cells were assessed. The patients were treated with combination chemotherapy and have been followed for 29–60 (median 52) months or until death. The survival curve had a steep fall during the first 2 yr. Between 2–5 yr after treatment there was a flattening of the curve and survival seemed to be similar to the survival expected for a Swedish population matched for age and sex. 11 patients died with 2 yr and 7 patients have survived for a longer period. Age, histopathologic classification and clinical stages were comparable in short‐term and long‐term survivors and treatment was not more aggressive for the long‐term survivors. The LIs were significantly higher (median 8.2) in short‐term survivors than in the long‐term survivors (median 1.4). Long‐term survival following combination chemotherapy of advanced NHL of unfavourable histology seems to be achieved mainly in patients with a low proliferative activity of the lymphoma cells. It is suggested that in NHL a high proliferative activity may facilitate the generation of new mutants and that some of these are spontaneously resistant to various chemotherapeutic drugs.
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| 15. |
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| 16. |
- Ekberg, Jenny, et al.
(author)
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Expression of cyclin A1 and cell cycle proteins in hematopoietic cells and acute myeloid leukemia and links to patient outcome
- 2005
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In: European Journal of Haematology. - : Wiley-Blackwell Publishing Inc.. - 0902-4441 .- 1600-0609. ; 75:2, s. 106-115
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Journal article (peer-reviewed)abstract
- Abnormal expression of several key regulators essential for G1/S transitions has been implicated in tumorigenesis. A critical role of cyclin A1 in the development of acute myeloid leukemia (AML) has previously been demonstrated in transgenic mice. Our present study focused on the expression and prognostic significance of cyclin A1 and a panel of cell cycle regulatory proteins including cyclin A2, cyclin B1, cyclin E, CDK1, CDK2, p21 and p27 in bone marrow samples from 40 patients with AML. Freshly isolated CD34+ hematopoietic cells and bone marrow samples from 10 healthy donors were also assessed for cell type- and subcellular-specific expression of the cell cycle regulatory proteins. The level of cyclin A1 expression was the only factor that showed a significant correlation with patient outcome. In log-rank test stratified by levels of cyclin A1 expression, patients with high levels of cyclin A1 had significantly worse overall survival (OS) (P = 0.012) compared to those with low levels. Further, patients with high levels of cyclin A1 had significantly lower disease-free survival (DFS) (P = 0.028). Multivariate analysis indicated that cyclin A1 protein expression was an independent prognostic factor for predicting DFS (P = 0.035) and OS (P = 0.045). No correlation between cyclin A1 expression and age was found. However, expression of cyclin A2, cyclin B1, cyclin E, CDK1, CDK2, p21 and p27 did not show prognostic significance in these AML patients.
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| 17. |
- Glimelius, Ingrid, 1975-, et al.
(author)
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Bulky disease is the most important prognostic factor in Hodgkin lymphoma stage IIB
- 2003
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 71:5, s. 327-33
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate treatment results for Hodgkin lymphoma (HL) patients younger than 60 yr in stage IIB, treated according to the Swedish National Care Programme. The intention was also to identify specific subgroups depending on the number of negative prognostic factors the patients have, in order to optimise and differentiate future treatment. In total, 99 patients with HL stage IIB, diagnosed between 1985 and 1994, have been analysed. There were 47 men and 52 women and the median age was 33 yr (range 17-59). Eighty-six patients presented with supradiaphragmatic disease and 13 with infradiaphragmatic. The HL specific and overall 10-yr survival was 73 and 65%, respectively. The HL-specific survival for patients in pathological stage IIB tended to be better, although not statistically significant than for clinical stage IIB, despite less chemotherapy (P = 0.1). The patients in stage IIB who were selected for laparotomy were, however, younger and with fewer negative prognostic factors. The only significant negative prognostic factor was bulky disease (P = 0.001). The following factors also tended to have a negative influence on the prognosis although not statistically significant: the International Prognostic Score, the number of involved lymph node stations, extranodal involvement and leucocyte count > 15 x 10(9)/L. In conclusion, we suggest that bulky disease should be taken into account when treating patients with stage IIB HL.
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| 18. |
- Hansson, Markus, et al.
(author)
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Biphenotypic bigenotypic lymphoma with simultaneous expression of PAX5/BSAP and B- and T-cell markers
- 2007
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 79:2, s. 159-165
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Journal article (peer-reviewed)abstract
- Lymphomas are currently categorized according to their origin from a B or T lymphocyte. Immature and less commonly mature (peripheral) lymphomas may harbor rearrangements of both the B- and T-cell antigen receptor genes (dual genotype or bigenotype). Rarely, cells in lymphoma with a single genotype simultaneously express both B- and T-cell markers (biphenotypic lymphomas). We discuss the diagnostic and clinical implications in the case of a 42-yr-old female with a peripheral CD30(+) lymphoma that displayed both characteristic B- and T-cell surface antigens and clonal rearrangement of B- and T-cell antigen receptor gene loci. Simultaneous nuclear expression of the transcription factor gene PAX5 suggested that this major driver of B-cell differentiation did not preclude expression of CD3 epsilon, generally assumed to be a T-cell associated antigen.
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| 19. |
- Hippe, E, et al.
(author)
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Nordic Myeloma Study Group, the first 15 years: Scientific collaboration and improvement of patient care
- 2005
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 74:3, s. 185-193
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Research review (peer-reviewed)abstract
- The accomplishments of the Nordic Myeloma Study Group (NMSG) during its first 15 yr are briefly surveyed, together with a discussion of principles guiding the group's clinical trials and of problems that need to be addressed in coming years. The group has so far carried out 12 clinical trials, comprising more than 2500 patients, spanning from minor phase II to large randomised phase III trials. At the time of writing, two randomised trials are running (comparing two doses of i.v. pamidronate, and melphalan-prednisone (MP) vs. MP-thalidomide to elderly patients). The group has strived for a simple organisation with much responsibility delegated to regional coordinators (Denmark 3, Norway 5, Sweden 5). With regard to trial design, the group has considered it important that studies are based on sound scientific questions, are simple to handle for the participants, population based, investigator initiated, include quality of life and health resources assessment as end-points, and can be used as basis for diverse scientific spin-off projects. Like other clinical trial groups, NMSG faces a number of challenges in coming years. The financial situation for independent investigator-initiated trials is far from satisfactory, especially with regard to the resource-consuming implementation of more stringent good clinical practice rules and ethical committee demands. NMSG has also encountered increasing difficulties in recruiting patients to recent trials, partly because of problems related to participating physicians (lack of support, laborious paper work, insufficient credit for participation). Solutions to these problems have to be found if industry-independent clinical trial groups are to survive.
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| 20. |
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| 21. |
- Khawaji, Mohammed, et al.
(author)
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Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life.
- 2012
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In: European Journal of Haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 88:4, s. 329-335
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Journal article (peer-reviewed)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.
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| 22. |
- Kling, S., et al.
(author)
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Moderate haemophilia B in a female carrier caused by preferential inactivation of the paternal X chromosome
- 1991
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 47:4, s. 257-261
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Journal article (peer-reviewed)abstract
- The case of a female with moderate haemophilia B is reported. She is the only affected member of her family, and factor IX RFLP analysis shows her to have inherited no maternal markers for polymorphisms located in the first intron and 8 Kb 3' of the polyadenylation signal (DdeI and HhaI, respectively). This clearly indicates a deletion involving at least the last 7 exons of the factor IX gene. Her other factor IX gene inherited from her healthy father is normal as her son is also healthy. This suggests the patient's haemophilia to be due to gross bias in the proportion of factor IX-producing cells with an inactive paternal X chromosome. Methylation studies on the 5' region of the PGK gene show that virtually all the patient's lymphocytes carry a hypermethylated and presumably an inactive paternal X chromosome. The reason for this bias in the activity of her two X chromosomes is not clear, as no chromosomal alterations were found.
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| 23. |
- Kling, S., et al.
(author)
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Origin of mutation in sporadic cases of haemophilia-B
- 1992
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 48:3, s. 142-145
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Journal article (peer-reviewed)abstract
- Of the 45 haemophilia-B patients registered at the haemophilia centre in Malmo, Sweden, 24 are the sole members of their families to be affected, and in 13 of these 24 cases, ascendant relatives are available for study. Detection of the gene defect showed the mutation to be de novo in the proband in 3 of these 13 cases, and inherited from a carrier mother in the remaining 10 cases. All 10 carrier mothers were shown to have de novo mutations, as the patients' grandfathers were phenotypically and/or haematologically normal, and the grandmothers were non-carriers. Seven restriction fragment length polymorphisms (RFLPs) of the factor IX gene were used to determine whether the de novo mutations of the 10 carrier mothers were of paternal or maternal origin. In 6/10 cases, the RFLP patterns were informative, and indicated the mutation to be of paternal origin.
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| 24. |
- Kristoffersson, Ulf, et al.
(author)
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Deletion of 14q in non‐Hodgkin's lymphoma
- 1990
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 44:4, s. 261-264
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Journal article (peer-reviewed)abstract
- Abstract: 6 patients with non‐Hodgkin's lymphoma [3 with small cell lymphocytic lymphoma of B‐cell type (SL), and 1 each with follicular centroblastic/centrocytic, centroblastic, and immunoblastic lymphoma] and with the acquired cytogenetic abnormalities del(14) (q22) or del(14) (q24) are described. An evaluation of these 6 cases and 41 other lymphatic neoplasms with 14q deletion known from the literature revealed that 37 had a breakpoint in bands q22 to q24. The deletions occur significantly more often in lymphomas of SL morphology and in the leukemic counterpart, chronic lymphocytic leukemia, than in other types of lymphatic malignancies (p< 0.001).
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| 25. |
- Landin, B., et al.
(author)
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Haemoglobin Koln as de novo mutations in Sweden : Diagnosis by PCR and specific enzymatic cleavage
- 1994
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In: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 52:3, s. 156-161
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Journal article (peer-reviewed)abstract
- Three independent cases of chronic haemolytic anaemia in Sweden have recently been demonstrated to be due to the unstable haemoglobin variant Hb Koln. The patients, all of whom have partially compensated chronic haemolytic anaemia, presented with aggravated haemolysis during acute infections in childhood. In one case, acute B19 parvovirus infection induced an aplastic crisis. The substitutions all seem to have occurred as de novo mutations. Diagnosis was based on haemoglobin instability testing and isoelectric focusing of haemoglobin dimers. The final identification procedure for the substitutions included extraction of DNA from whole blood, polymerase chain reaction (PCR) amplification of parts of the β-globin gene and nucleotide sequencing of the resulting material, or studies of restriction length polymorphisms (RFLPs) using the restriction endonucleases Mae II or Nla III. The use of PCR-RFLP is recommended as a valuable tool for diagnosing Hb Koln.
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