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- Wilking, N., et al.
(författare)
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Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy
- 2007
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 18:4, s. 694-700
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. Patients and methods: Five hundred and twenty-five women below theage of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. Results: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). Conclusion: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS. © 2007 Oxford University Press.
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- Stratmann, Svea, 1989-, et al.
(författare)
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Proteogenomic analysis of acute myeloid leukemia associates relapsed disease with reprogrammed energy metabolism both in adults and children
- 2023
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 37:3, s. 550-559
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Tidskriftsartikel (refereegranskat)abstract
- Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance largely determine the outcome for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment remain to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using mass spectrometry-based in-depth proteomics. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.
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- Onatsu, J., et al.
(författare)
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Tau, S100B and NSE as Blood Biomarkers in Acute Cerebrovascular Events
- 2020
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Ingår i: In Vivo. - : Anticancer Research USA Inc.. - 0258-851X .- 1791-7549. ; 34:5, s. 2577-2586
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aim: We aimed to analyze the diagnostic value of total tau (T- tau), S-100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) as blood-based biomarkers in acute ischemic stroke (AIS) or transient ischemic attack (TIA), and their correlation with symptom severity, infarct size, etiology and outcome. Patients and Methods: A total of 102 patients with stroke and 35 with TIA were analyzed. Subacute (63.8 +/- 50.1 h) plasma T-tau was measured with the single-molecule array (Simoa) method and NSE and S100B were evaluated for comparison. We evaluated biomarkers associations with: (i) diagnosis of AIS or TIA, (ii) cerebral infarction volume in the brain computed tomography, (iii) stroke etiology, (iv) clinical stroke severity and (iv) functional outcome after three months. Results: T-tau was higher in patients with stroke (1.0 pg/ml (IQR=0.3-2 2)] than with TIA (05 pg/ml (IQR=0.2- 1 .0), p=0.02] . The levels of S100B were also increased in stroke [0.082 mu g/l (IQR=0.049-0.157)] patients compared to TIA patients (0.045 mu g/l (IQR=0.03 -0.073 ), p<0.001]. However, when the results were adjusted for confounders, significance was lost. Serum levels of NSE among patients with AIS [11.85 mu g/l (IQR=9.30-16.14)] compared to those with TIA (10.96 mu g/l (IQR=7 .98-15.33), p=0.301 were equal. T-tau and S100B concentrations significantly correlated with cerebral infarction volume (r=0.412, p<0.001) and (r=0.597, p<0.001), also after corrections (p<0.001). mRS scores at three-month follow-up correlated with T-tau (r=0.248, p=0.016) and S100B concentrations (r=0.205, p=0.045). Conclusion: For the diagnosis of TIA vs. AIS, blood T-tau and S100B concentrations discriminated only modestly. Additionally, groups were not separable after measuring of T-tau and S100B levels in the blood. T-tau and S100B concentrations correlated with the infarct size, but were not alone predictive for functional outcome at 3 months.
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- Birgersson, Sofia, 1976, et al.
(författare)
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Population pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Burkina Faso: An open label trial [version 2; peer review: 2 approved]
- 2020
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Ingår i: Wellcome Open Research. - : F1000 Research Ltd. - 2398-502X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malaria during pregnancy is a major health risk for both the mother and the foetus. Pregnancy has been shown to influence the pharmacokinetics of a number of different antimalarial drugs. This might lead to an under-exposure in these patients which could increase the risk of treatment failure and the development of drug resistance. The study aim was to evaluate the pharmacokinetics of artesunate and dihydroartemisinin in pregnant and non-pregnant patients using a population modelling approach. Methods: Twenty-four women in their second and third trimester of pregnancy and twenty-four paired non-pregnant women, all with uncomplicated P. falciparum malaria, were enrolled in this study. Treatment was a fixed-dose combination of oral artesunate and mefloquine once daily for three days. Frequent blood samples were collected and concentration-time data for artesunate and dihydroartemisinin were analysed simultaneously using nonlinear mixed-effects modelling. Results: Artesunate pharmacokinetics was best described by a transit-compartment absorption model followed by a one-compartment disposition model under the assumption of complete in vivo conversion of artesunate into dihydroartemisinin. Dihydroartemisinin pharmacokinetics was best described by a one-compartment disposition model with first-order elimination. Pregnant women had a 21% higher elimination clearance of dihydroartemisinin, compared to non-pregnant women resulting in proportionally lower drug exposure. In addition, initial parasitaemia and liver enzyme levels (alanine aminotransferase) were found to affect the relative bioavailability of artesunate. Conclusions: Results presented here show a substantially lower drug exposure to the antimalarial drug dihydroartemisinin during pregnancy after standard oral treatment of artesunate and mefloquine. This might result in an increased risk of treatment failure and drug resistance development especially in low transmission settings where relative immunity is lower. Trial registration: ClinicalTrials.gov NCT00701961 (19/06/2008). © 2020 Birgersson S et al.
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- Juliusson, Gunnar, et al.
(författare)
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Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival.
- 2006
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 20:1, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Combination chemotherapy may induce remission from acute myeloid leukemia (AML), but validated criteria for treatment of elderly are lacking. The remission intention ( RI) rate for elderly patients, as reported to the Swedish Leukemia Registry, was known to be different when comparing the six health care regions, but the consequences of different management are unknown. The Leukemia Registry, containing 1672 AML patients diagnosed between 1997 and 2001, with 98% coverage and a median follow-up of 4 years, was completed with data from the compulsory cancer and population registries. Among 506 treated and untreated patients aged 70-79 years with AML (non-APL), there was a direct correlation between the RI rate in each health region ( range 36-76%) and the two-year overall survival, with no censored observations (6-21%) ( v 2 for trend = 11.3, P < 0.001; r(2) = 0.86, P < 0.02, nonparametric). A 1-month landmark analysis showed significantly better survival in regions with higher RI rates ( P = 0.003). Differences could not be explained by demographics, and was found in both de novo and secondary leukemias. The 5-year survival of the overall population aged 70-79 years was similar between the regions. Survival of 70-79-year-old AML patients is better in regions where more elderly patients are judged eligible for remission induction.
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| 10. |
- Juliusson, Gunnar, et al.
(författare)
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Increased remissions from one course for intermediate-dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population-based phase II study
- 2003
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 123:5, s. 810-818
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Tidskriftsartikel (refereegranskat)abstract
- Cladribine has single-drug activity in acute myeloid leukaemia (AML), and may enhance the formation of the active metabolite (ara-CTP) of cytosine arabinoside (ara-C). To evaluate the feasibility of adding intermittent cladribine to intermediate-dose ara-C (1 g/m(2)/2 h) b.i.d. for 4 d with idarubicin (CCI), we performed a 2:1 randomized phase II trial in AML patients aged over 60 years. Primary endpoints were time to recovery from cytopenia and need for supportive care following the first course. Sixty-three patients (median 71 years, range 60-84 years) were included, constituting 72% of all eligible patients. Toxicity was limited, with no differences between the treatment arms. The early toxic death rate was 11%. The median time to recovery from neutropenia and thrombocytopenia was 22 and 17 d from the start of course no. 1, respectively, and the requirement for platelet and red cell transfusions was four and eight units respectively. Patients had a median of 8 d with fever over 38degreesC, and 17 d with intravenous antibiotic treatment. The overall complete remission (CR) rate was 62%, with 51% CR from one course of CCI in comparison with 35% for the two-drug therapy (P = 0.014). The median survival with a 2-year follow-up was 14 months, and the 2-year survival was over 30%, with no differences between the treatment arms. Considering the median age and our population-based approach, the overall results are encouraging.
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