| 1. |
- Albertsen, Elena, et al.
(författare)
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Using ecological context to interpret spatiotemporal variation in natural selection
- 2021
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Ingår i: Evolution. - : Wiley. - 0014-3820 .- 1558-5646. ; 75:2, s. 294-309
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Tidskriftsartikel (refereegranskat)abstract
- Spatiotemporal variation in natural selection is expected, but difficult to estimate. Pollinator-mediated selection on floral traits provides a good system for understanding and linking variation in selection to differences in ecological context. We studied pollinator-mediated selection in five populations of Dalechampia scandens (Euphorbiaceae) in Costa Rica and Mexico. Using a nonlinear path-analytical approach, we assessed several functional components of selection, and linked variation in pollinator-mediated selection across time and space to variation in pollinator assemblages. After correcting for estimation error, we detected moderate variation in net selection on two out of four blossom traits. Both the opportunity for selection and the mean strength of selection decreased with increasing reliability of cross-pollination. Selection for pollinator attraction was consistently positive and stronger on advertisement than reward traits. Selection on traits affecting pollen transfer from the pollinator to the stigmas was strong only when cross-pollination was unreliable and there was a mismatch between pollinator and blossom size. These results illustrate how consideration of trait function and ecological context can facilitate both the detection and the causal understanding of spatiotemporal variation in natural selection.
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| 2. |
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| 3. |
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| 4. |
- Albertsen, Thomas, et al.
(författare)
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Describing Ontology Applications
- 2007
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Ingår i: Proceedings of the 4th Annual European Semantic Web Conference (ESWC 2007).
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Konferensbidrag (refereegranskat)abstract
- Semantic Web technologies are finally, after a few years of infancy, truly entering the business world to support the growing needs of computer aided information selection and processing. There are already quite well-defined development processes and methods in the software engineering field to handle the construction of large scale and complex enterprise systems, and to reuse knowledge in different software domains patterns are considered to be common practise. Patterns can be described on different levels of abstraction, but the patterns in the focus of this paper are on the software architecture level. In this paper we present a definition of the notion ”ontology application pattern”, as a special form of software architecture patterns describing an ontology-based system. We also show how such patterns, as well as the description of the pattern instantiations, can be described using a modified architecture description language.
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| 5. |
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| 6. |
- Albertsen, Thomas, et al.
(författare)
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Modelling Network-based Defence : Success and Failure of an Enterprise Modelling Endeavour
- 2010
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Ingår i: The Practice of Enterprise Modeling. - Berlin : Springer. - 9783642167812 ; , s. 121-129
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Konferensbidrag (refereegranskat)abstract
- Research projects have an inherent risk of failure, and learning howto cope with the risk is an important task for everyone involved. In order to doso it is necessary to share the knowledge of the experiences done during andafter the project. This paper investigates a recently completed enterprisemodeling research project and contributes with lessons learned andrecommendations for future enterprise modeling projects.
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| 7. |
- Albertsen, Thomas, et al.
(författare)
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The Practice of Competence Modelling
- 2010
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Ingår i: The Practice of Enterprise Modeling. - Berlin : Springer. - 9783642167812 ; , s. 106-120
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Konferensbidrag (refereegranskat)abstract
- A clear understanding of the organizational competences of anenterprise and the underlying individual competences and the competencedevelopment needs has become more and more important for many industrialareas as a foundation for competence supply processes and adjustment tochanging market conditions. Competence modelling, i.e. the use of enterprisemodelling techniques for capturing existing and describing desiredorganisational and individual competences in enterprises, offers importantcontributions to this. In the last years, the authors of the paper have performed anumber of competence modelling cases, which revealed different characteristicsand resulted in lessons learned. This paper presents an examination of differentcharacteristics of competence modelling cases, and recommendations andlessons learned from these cases for the practice of competence modelling.
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| 8. |
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| 9. |
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| 10. |
- Bjerner, Johan, et al.
(författare)
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Baseline Serum Prostate-specific Antigen Value Predicts the Risk of Subsequent Prostate Cancer Death-Results from the Norwegian Prostate Cancer Consortium.
- 2023
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Ingår i: European urology. - 1873-7560 .- 0302-2838.
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Tidskriftsartikel (refereegranskat)abstract
- Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality.To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death.The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176099 men (predefined age strata: 40-54 and 55-69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005.Baseline PSA.We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5-0.9, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method.The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0-3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40-54 and 55-69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation.We replicated prior studies that baseline PSA at age 40-69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15-20 yr.A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man's risk of dying from prostate cancer in the next two decades.
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| 11. |
- Donovan, Michael J., et al.
(författare)
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Personalized prediction of tumor response and cancer progression on prostate needle biopsy
- 2009
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 182:1, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. MATERIALS AND METHODS: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. RESULTS: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). CONCLUSIONS: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions.
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| 12. |
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| 13. |
- Gottschalk Højfeldt, Sofie, et al.
(författare)
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Relapse risk following truncation of PEG-asparaginase in childhood acute lymphoblastic leukemia.
- 2021
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 137:17, s. 2373-2382
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Tidskriftsartikel (refereegranskat)abstract
- Truncation of asparaginase treatment due to asparaginase related toxicities or silent inactivation (SI) is common and may increase relapse risk in acute lymphoblastic leukemia (ALL). We investigated relapse risk following suboptimal asparaginase exposure among 1401 children aged 1-17 years, diagnosed with ALL between July 2008 and February 2016, and treated according to the NOPHO ALL2008 protocol including extended asparaginase exposure (1,000 IU/m2 intramuscularly weeks 5 to 33). Patients were included with delayed entry at their last administered asparaginase treatment or detection of SI and followed until relapse, death, secondary malignancy, or end of follow-up (median: 5.71 years, interquartile range: 4.02-7.64). In a multiple Cox model comparing patients with (n=358) and without (n=1043) truncated asparaginase treatment due to clinical toxicity, the adjusted relapse-specific hazard ratio (aHR) was 1.33 (95% confidence interval [CI]: 0.86-2.06, P=0.20). In a substudy including only patients with information on enzyme activity (n=1115), the 7-year cumulative incidence of relapse for the 301 patients with truncation of asparaginase treatment or SI (157 hypersensitivity, 53 pancreatitis, 14 thrombosis, 31 other, 46 SI) was 11.1% (95% CI: 6.9-15.4) versus 6.7% (95% CI: 4.7-8.6) for the 814 remaining patients. The relapse-specific aHR was 1.69 (95% CI: 1.05-2.74, P=0.03). The unadjusted bone-marrow relapse-specific HR was 1.83 (95% CI: 1.07-3.14, P=0.03) and 1.86 (95% CI: 0.90- 3.87, P=0.095) for any CNS relapse. These results emphasize the importance of therapeutic drug monitoring and appropriate adjustment of asparaginase therapy when feasible.
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| 14. |
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| 15. |
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| 16. |
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| 17. |
- Levinsen, Mette, et al.
(författare)
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Leukemic blasts are present at low levels in spinal fluid in one-third of childhood acute lymphoblastic leukemia cases
- 2016
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:11, s. 1935-1942
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system (CNS) involvement is associated with relapse in childhood acute lymphoblastic leukemia (ALL) and is a diagnostic challenge. Procedure: In a Nordic/Baltic prospective study, we assessed centralized flow cytometry (FCM) of locally fixed cerebrospinal fluid (CSF) samples versus local conventional cytospin-based cytology (CC) for detecting leukemic cells and evaluating kinetics of elimination of leukemic cells in CSF. Results: Among 300 patients with newly diagnosed ALL, 87 (29%) had CSF involvement by FCM, while CC was positive in 30 (10%) of 299 patients with available CC data (P < 0.001). Patients with FCM+/CC+ had higher CSF leukemic blast counts compared to patients positive by FCM only (medians: 0.10 vs. 0.017 leukemic blasts/μl, P = 0.006). Patients positive by FCM had higher white blood cell counts in peripheral blood than patients negative by FCM (medians: 45 × 109/l vs. 10 × 109/l, P < 0.001), were younger (medians: 3 years vs. 4 years, P = 0.03), and more frequently had T-cell ALL (18/87 vs. 16/213, P = 0.001). At treatment day 15, five of 52 patients (10%) who had CSF positive by FCM at diagnosis remained so despite at least two doses of weekly intrathecal chemotherapy. Conclusions: Longer follow-up is needed to clarify whether FCM positivity has prognostic significance and is an indicator for intensified CNS-directed therapy.
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| 18. |
- Lynggaard, Line Stensig, et al.
(författare)
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Asparaginase enzyme activity levels and toxicity in childhood acute lymphoblastic leukemia : a NOPHO ALL2008 study
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:1, s. 138-147
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Tidskriftsartikel (refereegranskat)abstract
- Asparaginase treatment is a mainstay in contemporary treatment of acute lymphoblastic leukemia (ALL), but substantial asparaginase-related toxicity may lead to jeopardized protocol compliance and compromises survival. We investigated the association between risk of asparaginase-associated toxicities (AspTox) and asparaginase enzyme activity (AEA) levels in 1155 children aged 1.0 to 17.9 years, diagnosed with ALL between July 2008 and March 2016, and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. Patients with >= 2 blood samples for AEA measurement drawn 14 +/- 2 days after asparaginase administration were included (6944 trough values). AEA was measurable (or >0 IU/L) in 955 patients, whereas 200 patients (17.3%) had asparaginase inactivation and few AspTox recorded. A time-dependent multiple Cox model of time to any first asparaginase-associated toxicity adjusted for sex and age was used. For patients with measurable AEA, we found a hazard ratio (HR) of 1.17 per 100 IU/L increase in median AEA (95% confidence interval [CI], 0.98-1.41; P = .09). For pancreatitis, thromboembolism, and osteonecrosis, the HRs were 1.40 (95% CI, 1.12-1.75; P = .002), 0.99 (95% CI, 0.70-1.40; P = .96), and 1.36 (95% CI, 1.04-1.77; P = .02) per 100 IU/L increase in median AEA, respectively. No significant decrease in the risk of leukemic relapse was found: HR 0.88 per 100 IU/L increase in AEA (95% CI, 0.66-1.16; P = .35). In conclusion, these results emphasize that overall AspTox and relapse are not associated with AEA levels, yet the risk of pancreatitis and osteonecrosis increases with increasing AEA levels.
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| 19. |
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| 20. |
- Raja, Raheel A, et al.
(författare)
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Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol.
- 2014
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Ingår i: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 165:1, s. 126-133
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Tidskriftsartikel (refereegranskat)abstract
- L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase-intensive protocol has been poorly reported. Children (1-17years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000iu/m(2) /dose at 2-6weeks intervals, with a total of 30weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1-13), and 11d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re-exposed to L-asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re-exposure to PEG-asparaginase in ALL patients with mild AAP seems safe.
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| 21. |
- Rank, Cecilie U., et al.
(författare)
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Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age
- 2020
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Ingår i: Journal of Clinical Oncology. - Alexandria : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:2, s. 145-154
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored.PATIENTS AND METHODS: We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol.RESULTS: Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse.CONCLUSION: Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse.
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| 22. |
- Rank, Cecilie Utke, et al.
(författare)
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Thromboembolism in acute lymphoblastic leukemia : results of NOPHO ALL2008 protocol treatment in patients aged 1 to 45 years
- 2018
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Ingår i: Blood. - : AMER SOC HEMATOLOGY. - 0006-4971 .- 1528-0020. ; 131:22, s. 2475-2484
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Tidskriftsartikel (refereegranskat)abstract
- Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P < .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P < .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P < .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P = .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged (lymph nodes), 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P < .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P = .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P <= .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.
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| 23. |
- Ranta, Susanna, et al.
(författare)
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Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology
- 2015
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 168:4, s. 547-552
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Tidskriftsartikel (refereegranskat)abstract
- We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%. Sixteen of the thromboses were related to asparaginase and 16 to steroids. Most CSVTs occurred in the consolidation phase. Nearly all were treated with low molecular weight heparin without bleeding complications. Mortality related to CSVT directly or indirectly was 10%, emphasizing the importance of this complication.
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| 24. |
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| 25. |
- Tarasov, Vladimir, et al.
(författare)
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Ontology-Based Competence Management for Team Configuration
- 2007
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Ingår i: Holonic and Multi-Agent Systems for Manufacturing. - Berlin : Springer. - 9783540744788 ; , s. 401-410
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Konferensbidrag (refereegranskat)abstract
- When manufacturers, distributors and dealers need to collaborate, they form production networks because this provides significant advantages in production variety, flexibility and lead time. Production processes in such networks often spawn different specific tasks that are to be solved by the network members. This requires creation of a team able to tackle the identified problem. When dealing with multiple organizations and multiple processes within a complicated production network, trying to find a member that has required competence can be a laborious, time-consuming process. Developing and main-taining competence profiles of all the relevant parties associated with produc-tion can significantly reduce the time. The paper proposes an approach to team configuration based on competence profiles. The approach utilizes such tech-nologies as ontology management, context management and profiling. Using ontological representation makes it possible to identify those team members who are best suited for the task by ontology matching.
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| 26. |
- Thastrup, Maria, et al.
(författare)
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Flow cytometric detection of leukemic blasts in cerebrospinal fluid predicts risk of relapse in childhood acute lymphoblastic leukemia : a Nordic Society of Pediatric Hematology and Oncology study
- 2020
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 34:2, s. 336-346
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) involvement by cytospin is associated with increased risk of relapse in childhood acute lymphoblastic leukemia. We investigated if flow cytometric analysis of cerebrospinal fluid (CSF) at diagnosis improves the prediction of relapse. This prospective cohort study included patients (1.0-17.9 years) treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. CSF flow cytometry samples were obtained at 17 centers, preserved with Transfix (R), and analyzed at a central laboratory. One-hundred and seventy-one (25.4%) of 673 patients were positive by flow cytometry (CNSflow+). The 4-year cumulative incidence of relapse was higher for patients with cytospin positivity (CNScyto+) (17.1% vs. 7.5%), CNSflow+ (16.5% vs. 5.6%), and cytospin and/or flow positivity (CNScomb+) (16.7% vs. 5.1%). In Cox regression analysis stratified by immunophenotype and minimal residual disease day 29 and adjusted by sex, predictors of relapse were age (hazard ratio [HR] 1.1, 95% CI 1.1-1.2, P < 0.001), white blood cell count at diagnosis (HR 1.4, 95% CI 1.1-1.6, P < 0.001), and CNScomb+ (HR 2.2, 95% CI 1.0-4.7, P = 0.042). Flow cytometric analysis of CSF improves detection of CNS leukemia, distinguishes patients with high and low risk of relapse, and may improve future risk stratification and CNS-directed therapy.
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| 27. |
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| 28. |
- Tulstrup, Morten, et al.
(författare)
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Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial.
- 2018
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 100:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- This randomized controlled trial tested the hypothesis that children with non-high-risk acute lymphoblastic leukemia could benefit from individualized 6-mercaptopurine increments during consolidation therapy (NCT00816049). Primary and secondary end points were end of consolidation minimal residual disease (MRD) positivity and event-free survival.392 patients were randomized to experimental and 396 to standard therapy. Patients allocated to standard therapy received oral 6-mercaptopurine (25mg/m(2) /day) from days 30 to 85, while the experimental arm received stepwise increments of additional 25mg/m(2) /day beginning on days 50 and/or 71 unless dose-limiting myelosuppression had occurred.In the experimental arm, 166 patients (42%) received one dose increment, and 62 (16%) received two. Fifty-seven of 387 (15%) patients in the experimental arm were MRD positive at end of consolidation vs 77 of 389 (20%) in the control arm (P=.08). Five-year probability of event-free survival was 0.89 (95% CI: 0.85-0.93) in the experimental arm vs 0.93 (0.90-0.96) in the control arm (P=.13). The median accumulated length of 6-mercaptopurine treatment interruptions was 7 (IQR 2-12) in the experimental arm vs 4 (IQR 0-10) in the control arm (P=.002).This study found no benefit from individualized 6-mercaptopurine increments compared to standard therapy.
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| 29. |
- Tulstrup, Morten, et al.
(författare)
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Parents' and Adolescents' Preferences for Intensified or Reduced Treatment in Randomized Lymphoblastic Leukemia Trials.
- 2016
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 63:5, s. 865-871
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Tidskriftsartikel (refereegranskat)abstract
- When offered participation in clinical trials, families of children with cancer face a delicate balance between cure and toxicity. Since parents and children may perceive this balance differently, this paper explores whether adolescent patients have different enrollment patterns compared to younger children in trials with different toxicity profiles.
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| 30. |
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