| 1. |
- Gimsing, Peter, et al.
(författare)
-
Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial
- 2010
-
Ingår i: LANCET ONCOLOGY. - : Elsevier Science B.V., Amsterdam.. - 1470-2045 .- 1474-5488. ; 11:10, s. 973-982
-
Tidskriftsartikel (refereegranskat)abstract
- Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. Methods This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials. gov, number NCT00376883. Findings From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62.9-70.0) in the 90 mg group and 68 points (64.6-71.4) in the 30 mg group (95% CI of difference -6.6 to 3.3; p=0.52). Median time to first skeletal-related event in patients who had such an event was 9.2 months (8.1-10.7) in the 90 mg group and 10-2 months (7.3-14.0) in the 30 mg group (p=0.63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. Interpretation Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.
|
|
| 2. |
- Baccarani, Michele, et al.
(författare)
-
European LeukemiaNet recommendations for the management of chronic myeloid leukemia : 2013
- 2013
-
Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:6, s. 872-884
-
Forskningsöversikt (refereegranskat)abstract
- Advances in chronic myeloid leukemia treatment, particularly regarding tyrosine kinase inhibitors, mandate regular updating of concepts and management. A European LeukemiaNet expert panel reviewed prior and new studies to update recommendations made in 2009. We recommend as initial treatment imatinib, nilotinib, or dasatinib. Response is assessed with standardized real quantitative polymerase chain reaction and/or cytogenetics at 3, 6, and 12 months. BCR-ABL1 transcript levels <= 10% at 3 months, <1% at 6 months, and <= 0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure, mandating a change in treatment. Similarly, partial cytogenetic response (PCyR) at 3 months and complete cytogenetic response (CCyR) from 6 months onward define optimal response, whereas no CyR (Philadelphia chromosome-positive [Ph1]>95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure. Between optimal and failure, there is an intermediate warning zone requiring more frequent monitoring. Similar definitions are provided for response to second-line therapy. Specific recommendations are made for patients in the accelerated and blastic phases, and for allogeneic stem cell transplantation. Optimal responders should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved. (Blood. 2013; 122(6):872-884)
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Jönsson, Sofia, et al.
(författare)
-
Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro.
- 2012
-
Ingår i: Journal of bone and mineral metabolism. - 1435-5604. ; 30:1, s. 119-23
-
Tidskriftsartikel (refereegranskat)abstract
- Altered bone metabolism has been reported in patients with chronic myeloid leukemia treated with the tyrosine kinase inhibitor imatinib. Several studies have shown that imatinib inhibits the differentiation and activity of osteoclasts in vitro, whereas the effects of imatinib on osteoblast differentiation are less clear. In this study osteoblast differentiation was induced in human mesenchymal stem cells (hMSCs) by treatment with bone morphogenetic protein 2 in vitro. Imatinib inhibited proliferation of hMSCs in a dose-dependent manner. Even though imatinib promoted early osteoblast differentiation assessed by alkaline phosphate activity, mineralization measured by Alizarin Red staining (ARS) was reduced by imatinib. Moreover, the inhibitory effect of imatinib on mineralization was most prominent at low concentrations of imatinib. When we measured the relative mRNA expression levels of Runx2, we found that Runx2 expression was higher in imatinib-treated (5μM) cultures at early time points during differentiation. On the other hand, the expression of Osterix late during differentiation was lower in imatinib-treated (5μM) cultures, corresponding to the ARS results. Thus, the effect of imatinib on osteoblast differentiation is not only dependent on the drug concentration, but indeed also on the maturation stage of the cells. This finding might partly explain why previous studies on the effects of imatinib osteoblast differentiation have shown different results.
|
|
| 6. |
- Koskenvesa, Perttu, et al.
(författare)
-
Imatinib and pegylated IFN-alpha 2b discontinuation in first-line chronic myeloid leukemia patients following a major molecular response
- 2014
-
Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 92:5, s. 413-420
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives Previous studies indicate that 40-50% of patients with chronic myeloid leukemia in prolonged complete molecular remission may discontinue imatinib therapy without imminent relapse. The combination of pegylated interferon-alpha (Peg-IFN-alpha 2b) and imatinib may increase the rate of successful discontinuation. Methods In this pilot study, we prospectively stopped imatinib from patients (n=12) who had achieved major molecular response (MMR) after >= 12months of treatment with either imatinib or imatinib+Peg-IFN-alpha 2b. Molecular monitoring was carried out monthly for BCR-ABL1. In addition, analyses of lymphocyte immunophenotype, function, and plasma cytokines were performed. Results In the monotherapy group, 5/6 patients lost MMR within 4months. One patient remains to date in MR4.0 61months after discontinuation. In the combination therapy group, 2/6 patients relapsed within 4months while still receiving Peg-IFN-alpha 2b. Four of six patients were able to discontinue both treatments, but three of these patients relapsed after 3months. One patient is still in sustained MR4.0 at 58months off all treatment. All relapsed patients re-responded to imatinib. The two successfully discontinued patients had either an increased number of NK-cells or functionally active T-cells. Conclusions A higher frequency of relapsed patients in our study in comparison with other studies may be due to the shorter duration of imatinib treatment prior to discontinuation. However, in selected patients with an active immune system, even a short duration of TKI therapy (<2yr) may allow for therapy discontinuation but this needs to be confirmed in larger prospective studies.
|
|
| 7. |
- Kreutzman, Anna, et al.
(författare)
-
Killer-cell immunoglobulin-like receptor gene profile predicts good molecular response to dasatinib therapy in chronic myeloid leukemia
- 2012
-
Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 40:11, s. 906-913
-
Tidskriftsartikel (refereegranskat)abstract
- Tyrosine kinase inhibitors have greatly improved the prognosis of chronic myeloid leukemia (CML). In addition to direct kinase inhibition, their effects can also be mediated through immune modulation, such as expansion of cytotoxic T and natural-killer cells observed during dasatinib therapy. As natural-killer cell and partially CD8(+) T-cell function are regulated by killer immunoglobulin-like receptors (KIRs), we studied whether the KIR gene profile is associated with clinical therapy response in dasatinib-treated CML patients (n = 191). In first-line patients, the absence of the inhibitory KIR2DL5A (p = 0.0489), 2DL5B (p = 0.030), and 2DL5all (p = 0.0272) genes were associated with improved molecular response at the 12-month time point. In addition, the same trend was seen with two activating KIR genes, 2DS1 (p = 0.061) and 2DS2 (p = 0.071). Furthermore, when patients were clustered into two groups by their KIR gene profile, the BCR-ABL1 transcript levels differed significantly between the groups (p = 0.047), showing that patients who lacked several KIR genes had better response. The comparison of first-line and second-line patients did not show any significant differences in either KIR or human leukocyte antigen genotypes. Our results show that immunogenetic factors, such as the KIR gene profile, can play a role in tyrosine kinase inhibitor therapy response. Additional studies are warranted to elucidate the functional significance of KIR genes associated with treatment outcomes. (C) 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
