| 21. |
- Hou, M, et al.
(författare)
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Impact of endogenous thrombopoietin levels on the differential diagnosis of essential thrombocythaemia and reactive thrombocytosis.
- 1998
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Ingår i: European journal of haematology. - 0902-4441. ; 61:2, s. 119-22
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Tidskriftsartikel (refereegranskat)abstract
- By using the newly commercialized Quantikine human TPO immunoassay, plasma thrombopoietin (TPO) concentrations were measured in 12 patients with essential thrombocythaemia (ET), 13 patients with reactive thrombocytosis (RT) and 11 healthy volunteers. For the healthy volunteers the mean plasma TPO concentration was 21.1+/-11.0 pg/ml. The mean plasma TPO concentration in the group of RT was slightly lower (16.4+/-8.6 pg/ml) but did not differ significantly from the control group. The mean plasma TPO concentration in ET patients (44.1+/-45.2 pg/ml) was significantly (p<0.05) higher than the mean for RT patients, but did not differ statistically from the mean of healthy volunteers. These data suggest a defective clearance of plasma TPO in patients with ET.
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| 22. |
- Hou, M, et al.
(författare)
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Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes.
- 1998
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Ingår i: British journal of haematology. - 0007-1048. ; 101:3, s. 420-4
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the diagnostic value of thrombopoietin (TPO, c-mpl ligand) measurements, and clarify the regulatory mechanisms of TPO in normal and in thrombocytopenic conditions, the plasma TPO concentration was determined in normal individuals (n = 20), umbilical cord blood (n = 40), chronic idiopathic thrombocytopenic purpura (ITP; n = 16), in severe aplastic anaemia (SAA; n = 3), chemotherapy-induced bone marrow hypoplasia (n = 10), myelodysplastic syndrome (MDS; n = 11), and sequentially during peripheral blood progenitor cell transplantation (n = 7). A commercially available ELISA and EDTA-plasma samples were used for the analysis. The plasma TPO concentration in the normals and umbilical cord blood were 52 +/- 12 pg/ml and 66 +/- 12 pg/ml, respectively. The corresponding values in patients with SAA and chemotherapy-induced bone marrow hypoplasia were 1514 +/- 336 pg/ml and 1950 +/- 1684 pg/ml, respectively, and the TPO concentration, measured sequentially after myeloablative chemotherapy and peripheral blood progenitor cell transplantation, was inversely related to the platelet count. In contrast, the plasma TPO recorded in patients with ITP (64 +/- 20 pg/ml) and MDS (68 +/- 23 pg/ml) were only slightly higher than normal levels. In conclusion, TPO levels were significantly elevated in patients in which bone marrow megakaryocytes and platelets in circulation were markedly reduced, whereas TPO levels were normal in ITP patients, and only slightly increased in the MDS patients. These latter patients displayed a preserved number of megakaryocytes in bone marrow biopsies. Our data support the suggestion that megakaryocyte mass affects the plasma TPO concentration. In thrombocytopenic patients a substantially increased plasma TPO implies deficient megakaryocyte numbers. However, TPO measurements do not distinguish between ITP and thrombocytopenia due to dysmegakaryopoiesis, as seen in MDS patients.
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| 23. |
- Johnsen, Hans E., et al.
(författare)
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Improved Survival for Multiple Myeloma in Denmark Based on Autologous Stem Cell Transplantation and Novel Drug Therapy in Collaborative Trials: Analysis of Accrual, Prognostic Variables, Selection Bias, and Clinical Behavior on Survival in More Than 1200 Patients in Trials of the Nordic Myeloma Study Group
- 2010
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Ingår i: Clinical Lymphoma, Myeloma & Leukemia. - 2152-2650. ; 10:4, s. 290-296
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Tidskriftsartikel (refereegranskat)abstract
- Background: An unexplained survival difference was observed in the Nordic Myeloma Study Group (NMSG) high-dose therapy trial 5/94 in Denmark compared with Sweden and Norway; however, this difference was eliminated in the subsequent NMSG trial 7/98. It was hypothesized that a detailed analysis of potential explanations would reveal important information for future designs of clinical trials for multiple myeloma (MM) patients in Denmark. Patients and Methods: The analysis is based on 3 consecutive clinical trials coordinated by NMSG from 1990 to 2000: NMSG 4/90 including 583 patients, NMSG 5/94 including 274 patients and NMSG 7/98 including 414 patients with newly diagnosed MM. Event-free and total survival rates were calculated according to the Kaplan-Meier method, and survival comparisons were made by the log-rank test. The Cox proportional hazards regression model was used to estimate the prognostic importance of selected variables. Results: The analysis revealed no differences in disease stages, prognostic variables, or inclusion bias at diagnosis between the 3 consecutive NMSG trials. However, the number of initial treatment failures was low, and post-relapse survival was superior in Swedish patients as compared to Danish patients. These differences were explained by a defensive clinical practice in Denmark during 1994-1997 for patients with poor risk refractory or relapsed disease. Conclusion: These initially observed differences were subsequently eliminated most likely as a consequence of international collaboration improving diagnosis, research infrastructure, clinical training, and education as planned within the European Myeloma Network (EMN).
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| 24. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma : a population-based study
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:24, s. 4991-4998
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70,991 and 20,161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.
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| 25. |
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| 26. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:9, s. 3582-3586
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma ( MM) have an increased risk of deep venous thrombosis (DVT), particularly when treated with immunomodulatory drugs. Recently, 2 small hospital-based studies observed persons with the MM precursor condition, monoclonal gammopathy of undetermined significance (MGUS), to be at increased risk of developing DVT. Among 4 196 197 veterans hospitalized at least once at US Veterans Affairs hospitals, we identified a total of 2374 cases of MGUS, and 39 272 persons were diagnosed with DVT ( crude incidence 0.9 per 1000 person-years). A total of 31 and 151 DVTs occurred among MGUS and MM patients, respectively ( crude incidence 3.1 and 8.7 per 1000 person-years, respectively; P <.01). Compared with the entire study population, the relative risk (RR) of DVT after a diagnosis of MGUS and MM was 3.3 (95% confidence interval [CI], 2.3-4.7) and 9.2 ( 95% CI, 7.9-10.8), respectively. The most prominent excess risk of DVT was found during the first year after diagnosis of MGUS ( RR = 8.4; 95% CI, 5.7-12.2) and MM ( RR = 11.6; 95% CI, 9.2-14.5). Among 229 MGUS cases (9.5%) that progressed to MM, only one person had a DVT diagnosis before transformation. Our findings suggest the operation of shared underlying mechanisms causing coagulation abnormalities among patients with MGUS and MM. (Blood. 2008; 112: 3582-3586)
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| 27. |
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| 28. |
- Kristinsson, Sigurdur Y., et al.
(författare)
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Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study
- 2012
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 97:6, s. 854-858
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Tidskriftsartikel (refereegranskat)abstract
- No comprehensive evaluation has been made to assess the risk of viral and bacterial infections among patients with monoclonal gammopathy of undetermined significance. Using population-based data from Sweden, we estimated risk of infections among 5,326 monoclonal gammopathy of undetermined significance patients compared to 20,161 matched controls. Patients with monoclonal gammopathy of undetermined significance had a 2-fold increased risk (P < 0.05) of developing any infection at 5- and 10-year follow up. More specifically, patients with monoclonal gammopathy of undetermined significance had an increased risk (P < 0.05) of bacterial (pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis, and meningitis), and viral (influenza and herpes zoster) infections. Patients with monoclonal gammopathy of undetermined significance with M-protein concentrations over 2.5 g/dL at diagnosis had highest risks of infections. However, the risk was also increased (P < 0.05) among those with concentrations below 0.5 g/dL. Patients with monoclonal gammopathy of undetermined significance who developed infections had no excess risk of developing multiple myeloma, Waldenstrom macroglobulinemia or related malignancy. Our findings provide novel insights into the mechanisms behind infections in patients with plasma cell dyscrasias, and may have clinical implications.
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| 29. |
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| 30. |
- Kristinsson, Sigurdur Y, et al.
(författare)
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Monoclonal gammopathy of undetermined significance and risk of skeletal fractures : a population-based study
- 2010
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 116:15, s. 2651-2655
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.
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