| 1. |
- Zeiser, R., et al.
(författare)
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Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:10, s. 2062-2068
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Tidskriftsartikel (refereegranskat)abstract
- Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n = 54, all grades III or IV) or SR-cGVHD (n = 41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
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| 2. |
- Snowden, JA, et al.
(författare)
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Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)
- 2020
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Ingår i: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 55:4, s. 681-694
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Tidskriftsartikel (refereegranskat)abstract
- In many healthcare settings, benchmarking for complex procedures has become a mandatory requirement by competent authorities, regulators, payers and patients to assure clinical performance, cost-effectiveness and safe care of patients. In several countries inside and outside Europe, benchmarking systems have been established for haematopoietic stem cell transplantation (HSCT), but access is not universal. As benchmarking is now integrated into the FACT-JACIE standards, the EBMT and JACIE established a Clinical Outcomes Group (COG) to develop and introduce a universal system accessible across EBMT members. Established systems from seven European countries (United Kingdom, Italy, Belgium, France, Germany, Spain, Switzerland), USA and Australia were appraised, revealing similarities in process, but wide variations in selection criteria and statistical methods. In tandem, the COG developed the first phase of a bespoke risk-adapted international benchmarking model for one-year survival following allogeneic and autologous HSCT based on current capabilities within the EBMT registry core dataset. Data completeness, which has a critical impact on validity of centre comparisons, is also assessed. Ongoing development will include further scientific validation of the model, incorporation of further variables (when appropriate) alongside implementation of systems for clinically meaningful interpretation and governance aiming to maximise acceptance to centres, clinicians, payers and patients across EBMT.
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| 3. |
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| 4. |
- Heck, J., et al.
(författare)
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Structure-property relationship in organometallic compounds regarding SHG
- 2007
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Ingår i: Linear and Nonlinear Optics of Organic Materials VII. - : SPIE - International Society for Optical Engineering. - 9780819468017 ; , s. R6530-R6530
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Konferensbidrag (refereegranskat)abstract
- Structure-property relationships based on experimental as well as theoretical results will be elucidated. For this purpose different dipolar organometallic compounds were synthesized and characterized. The alteration of the donor and acceptor termini in mono- and dinuclear sesquifulvalene complexes results in spectroscopic and even structural modifications. The structural and 1H NMR spectroscopic changes correlate with the experimentally obtained first hyperpolarizability. The potent electron-donating (D) group [(CpFeCO)2(μ-CO)(μ-C=CH-)] is combined with different electron-accepting units (A), yielding the push-pull complexes [(CpFeCO) 2(μ-CO)(μ-C=CH-CH=A)]. The extent of electron derealization within the π-bridge connecting the donor D and the acceptor A can be monitored by means of 1H NMR spectroscopy. A correlation between the 3J(Hβ-Hγ) coupling constants and the first hyperpolarizability is found, which very much resembles the dependence of the first hyperpolarizability on the bond length alternation. In order to elucidate the dependence of the NLO response on the conformation of triply branched NLOphores, a new series of dendritic D-π-A structures has been synthesized. A combined approach of experiments and computational predictions was applied both on the dendrimers and on the corresponding single-strand chromophores. These results demonstrate that theoretical calculations are able to reproduce experimental results and show the tendency of the effects due to structural changes.
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| 5. |
- Holtmann, J., et al.
(författare)
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Three-branched dendritic dipolar nonlinear optical chromophores, more than three times a single-strand chromophore?
- 2008
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 112:47, s. 14751-14761
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Tidskriftsartikel (refereegranskat)abstract
- To elucidate the dependence of the nonlinear optical (NLO) response on the conformation of triply branched derivatives, a new series of D-pi-A dendrimers has been synthesized. A combined approach of experiments (UV-vis and EOA measurements) and computational predictions (semiempirical and ab initio) was applied both on the dendrimers and on the corresponding single-strand chromophores. It has been shown that depending on the surrounding media the NLO activity of a flexible dendrimer can be very different. Two limiting cases are proposed: (i) the dendrimer resembles a solution of the corresponding single-strand chromophores with about 3-fold concentration, where the hyperpolarizability is the sum of the effect of three noninteracting single-strand subunits ("independent chromophores" limit); (ii) the dendrimers show nearly parallel or helical alignments of the single-strand subunits. Because of this change of conformation the NLO activity can be enhanced up to nine times the value of the "independent chromophores" limit and, thus, are more than a single strand chromophore. Conformers of dendrimers with interacting single-strand chromophores have been identified experimentally in nonpolar solutions by the EOA spectroscopy and possible structures have been revealed by numerical calculations, which could moreover show the tendency of the effects on the hyperpolarizability due to structural changes of the flexible dendritic architecture. Implications for future research developments are given to implement the "more than three times" concept.
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| 9. |
- Löwenberg, Bob, et al.
(författare)
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Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML : the HOVON-SAKK-132 trial
- 2021
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:4, s. 1110-1121
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Tidskriftsartikel (refereegranskat)abstract
- Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% +/- 2% standard error and overall survival, 54% = 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
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