| 1. |
|
|
| 2. |
- Abe, O, et al.
(författare)
-
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
-
Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
-
Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
|
|
| 3. |
|
|
| 4. |
- Taddei, C, et al.
(författare)
-
Repositioning of the global epicentre of non-optimal cholesterol
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 582:7810, s. 73-
-
Tidskriftsartikel (refereegranskat)abstract
- High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
|
|
| 5. |
- Quist-Paulsen, P., et al.
(författare)
-
T-cell acute lymphoblastic leukemia in patients 1-45 years treated with the pediatric NOPHO ALL2008 protocol
- 2020
-
Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:2, s. 347-357
-
Tidskriftsartikel (refereegranskat)abstract
- The NOPHO ALL2008 is a population-based study using an unmodified pediatric protocol in patients 1-45 years of age with acute lymphoblastic leukemia. Patients with T-ALL were given a traditional pediatric scheme if fast responding (minimal residual disease (MRD) < 0.1% day 29), or intensive block-based chemotherapy if slow responding (MRD > 0.1% day 29). Both treatment arms included pediatric doses of high-dose methotrexate and asparaginase. If MRD >= 5% on day 29 or >= 0.1% after consolidation, patients were assigned to allogeneic hematopoietic stem cell transplantation. The 5-year overall survival of the 278 T-ALL patients was 0.75 (95% CI 0.69-0.81), being 0.82 (0.74-0.88) for patients 1.0-9.9 years, 0.76 (0.66-0.86) for those 10.0-17.9 years, and 0.65 (0.55-0.75) for the older patients. The risk of death in first remission was significantly higher in adults (12%) compared with the 1-9 years group (4%). The MRD responses in the three age groups were similar, and only a nonsignificant increase in relapse risk was found in adults. In conclusion, an unmodified pediatric protocol in patients 1-45 years is effective in all age groups. The traditional pediatric treatment schedule was safe for all patients, but the intensive block therapy led to a high toxic death rate in adults.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Ekström, Andreas, et al.
(författare)
-
Electric quadrupole moments of the 2(1)(+) states in Cd-100,Cd-102,Cd-104
- 2009
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 80:5
-
Tidskriftsartikel (refereegranskat)abstract
- Using the REX-ISOLDE facility at CERN the Coulomb excitation cross sections for the 0(gs)(+)-> 2(1)(+) transition in the beta-unstable isotopes Cd-100,Cd-102,Cd-104 have been measured for the first time. Two different targets were used, which allows for the first extraction of the static electric quadrupole moments Q(2(1)(+)) in Cd-102,Cd-104. In addition to the B(E2) values in Cd-102,Cd-104, a first experimental limit for the B(E2) value in Cd-100 is presented. The data was analyzed using the maximum likelihood method. The provided probability distributions impose a test for theoretical predictions of the static and dynamic moments. The data are interpreted within the shell-model using realistic matrix elements obtained from a G-matrix renormalized CD-Bonn interaction. In view of recent results for the light Sn isotopes the data are discussed in the context of a renormalization of the neutron effective charge. This study is the first to use the reorientation effect for post-accelerated short-lived radioactive isotopes to simultaneously determine the B(E2) and the Q(2(1)(+)) values.
|
|
| 9. |
- Fynbo, J. P. U., et al.
(författare)
-
Galaxy counterparts of metal-rich damped Ly alpha absorbers - I. The case of the z=2.35 DLA towards Q2222-0946
- 2010
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 408:4, s. 2128-2136
-
Tidskriftsartikel (refereegranskat)abstract
- We have initiated a survey using the newly commissioned X-shooter spectrograph to target candidate relatively metal-rich damped Ly alpha absorbers (DLAs). Our rationale is that high-metallicity DLAs due to the luminosity-metallicity relation likely will have the most luminous galaxy counterparts. In addition, the spectral coverage of X-shooter allows us to search for not only Ly alpha emission, but also rest-frame optical emission lines. We have chosen DLAs where the strongest rest-frame optical lines ([O II], [O III], H beta and H alpha) fall in the near-infrared atmospheric transmission bands. In this first paper resulting from the survey, we report on the discovery of the galaxy counterpart of the z(abs) = 2.354 DLA towards the z = 2.926 quasar Q2222-0946. This DLA is amongst the most metal-rich z > 2 DLAs studied so far at comparable redshifts and there is evidence for substantial depletion of refractory elements on to dust grains. We measure metallicities from Zn II, Si II, Ni II, Mn II and Fe II of -0.46 +/- 0.07, -0.51 +/- 0.06, -0.85 +/- 0.06, -1.23 +/- 0.06 and -0.99 +/- 0.06, respectively. The galaxy is detected in the Ly alpha, [O III] lambda lambda 4959, 5007 and H alpha emission lines at an impact parameter of about 0.8 arcsec (6 kpc at z(abs) = 2.354). Based on the H alpha line, we infer a star formation rate of 10M(circle dot) yr(-1), which is a lower limit due to the possibility of slit loss. Compared to the recently determined H alpha luminosity function for z = 2.2 galaxies, the DLA-galaxy counterpart has a luminosity of L similar to 0.1L*(H alpha). The emission-line ratios are 4.0 (Ly alpha/H alpha) and 1.2 ([O III]/H alpha). In particular, the Ly alpha line shows clear evidence for resonant scattering effects, namely an asymmetric, redshifted (relative to the systemic redshift) component and a much weaker blueshifted component. The fact that the blueshifted component is relatively weak indicates the presence of a galactic wind. The properties of the galaxy counterpart of this DLA are consistent with the prediction that metal-rich DLAs are associated with the most luminous of the DLA-galaxy counterparts.
|
|
| 10. |
- Fynbo, J. P. U., et al.
(författare)
-
Galaxy counterparts of metal-rich damped Ly alpha absorbers - II. A solar-metallicity and dusty DLA at z(abs)=2.58
- 2011
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 413:4, s. 2481-2488
-
Tidskriftsartikel (refereegranskat)abstract
- This is the second paper of a series reporting on the results from a survey conducted with the ESO VLT/X-shooter spectrograph. We target high-metallicity damped Lyman alpha absorbers (DLAs) with the aim of investigating the relation between galaxies detected in emission and those detected in absorption. Here, we report on the discovery of the galaxy counterpart of the z(abs) = 2.58 DLA on the line-of-sight to the z = 3.07 quasar SDSS J 091826.16+163609.0 (hereafter Q 0918+1636). The galaxy counterpart of the DLA is detected in the [O iii] lambda 5007 and [O ii] lambda lambda 3726, 3729 emission lines redshifted into the NIR at an impact parameter of 2.0 arcsec (16 kpc at z = 2.58). Ly alpha emission is not detected down to a 3 Sigma detection limit of 5 x 10-18 erg s-1 cm-2, which, compared to the strength of the oxygen lines, implies that Ly alpha emission from this galaxy is suppressed by more than an order of magnitude. The DLA has one of the highest metallicities measured so far at comparable redshifts. We find evidence for substantial depletion of refractory elements on to dust grains. Fitting the main metal line component of the DLA, which is located at z(abs) = 2.5832, we measure the metal abundances from Zn ii, S ii, Si ii, Cr ii, Mn ii, Fe ii and Ni ii to be -0.12 +/- 0.05, -0.26 +/- 0.05, -0.46 +/- 0.05, -0.88 +/- 0.05, -0.92 +/- 0.05, -1.03 +/- 0.05 and -0.78 +/- 0.05, respectively. In addition, we detect absorption in the Lyman and Werner bands of molecular hydrogen (H(2)), which represents the first detection of H(2) molecules with X-shooter. The background quasar Q 0918+1636 is amongst the reddest QSOs at redshifts 3.02 < z < 3.12 from the SDSS catalogue. Its UV to NIR spectrum is well fitted by a composite QSO spectrum reddened by SMC-/LMC-like extinction curves at z(abs) = 2.58 with a significant amount of extinction given by A(V) approximate to 0.2 mag. This supports previous claims that there may be more metal-rich DLAs missing from current samples due to dust reddening of the background QSOs. The fact that there is evidence for dust both in the central emitting regions of the galaxy (as evidenced by the lack of Ly alpha emission) and at an impact parameter of 16 kpc (as probed by the DLA) suggests that dust is widespread in this system.
|
|
| 11. |
- Fynbo, J. P. U., et al.
(författare)
-
Galaxy counterparts of metal-rich damped Lyman-alpha absorbers - II. A solar-metallicity and dusty DLA at z_abs=2.58
- 2010
-
Annan publikation (populärvet., debatt m.m.)abstract
- [Abridged]. Here, we report on the discovery of the galaxy counterpart of the z_abs=2.58 DLA on the line-of-sight to the z=3.07 quasar SDSS J091826.16+163609.0. The galaxy counterpart of the DLA is detected in the OIII 5007 and OII 3726,3729 emission lines redshifted into the NIR at an impact parameter of 16 kpc. Ly-alpha emission is not detected. The upper limit implies that Ly-alpha emission from this galaxy is suppressed by more than an order of magnitude. The DLA is amongst the most metal-rich DLAs studied so far at comparable redshifts. We find evidence for substantial depletion of refractory elements onto dust grains. Fitting the main metal line component of the DLA, which is located at z_abs=2.5832 and accounts for at least 85% of the total column density of low-ionisation species, we measure metal abundances from ZnII, SII, SiII, CrII, MnII, FeII and NiII of -0.12, -0.26, -0.46, -0.88, -0.92, -1.03 and -0.78, respectively. In addition, we detect absorption in the Lyman and Werner bands of hydrogen, which represents the first detection of H_2 molecules with X-shooter. The background quasar Q0918+1636 is amongst the reddest QSOs at redshifts 3.02<3.12 from the SDSS catalogue. Its UV to NIR spectrum is well fitted by a composite QSO spectrum reddened by SMC/LMC-like extinction curves at z_abs=2.58 with a significant amount of extinction given by A_V = 0.2 mag. This supports previous claims that there may be more metal-rich DLAs missing from current samples due to dust reddening of the background QSOs. The fact that there is evidence for dust both in the central emitting regions of the galaxy (as evidenced by the lack of Ly-alpha emission) and at an impact parameter of 16 kpc (as probed by the DLA) suggests that dust is widespread in this system.
|
|
| 12. |
|
|
| 13. |
- Gustafsson, U O, et al.
(författare)
-
Pre-operative carbohydrate loading may be used in type 2 diabetes patients
- 2008
-
Ingår i: Acta Anaesthesiologica Scandinavica. - Malden, USA : Blackwell Publishing. - 0001-5172 .- 1399-6576. ; 52:7, s. 946-51
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Post-operative insulin resistance and hyperglycaemia are associated with an impaired outcome after surgery. Pre-operative oral carbohydrate loading (CHO) reduces post-operative insulin resistance with a reduced risk of hyperglycaemia during post-operative nutrition. Insulin-resistant diabetic patients have not been given CHO because the effects on pre-operative glycaemia and gastric emptying are unknown.Methods: Twenty-five patients (45-73 years) with type 2 diabetes [glycated haemoglobin (HbA1c) 6.2 +/- 0.2%, mean +/- SEM] and 10 healthy control subjects (45-72 years) were studied. A carbohydrate-rich drink (400 ml, 12.5%) was given with paracetamol 1.5 g for determination of gastric emptying.Results: Peak glucose was higher in diabetic patients than in healthy subjects (13.4 +/- 0.5 vs. 7.6 +/- 0.5 mM; P<0.01) and occurred later after intake (60 vs. 30 min; P<0.01). Glucose concentrations were back to baseline at 180 vs. 120 min in diabetic patients and healthy subjects, respectively (P<0.01). At 120 min, 10.9 +/- 0.7% and 13.3 +/- 1.2% of paracetamol remained in the stomach in diabetic patients and healthy, subjects respectively. Gastric half-emptying time (T50) occurred at 49.8 +/- 2.2 min in diabetics and at 58.6 +/- 3.7 min in healthy subjects (P<0.05). Neither peak glucose, glucose at 180 min, gastric T50, nor retention at 120 min differed between insulin (HbA1c 6.8 +/- 0.7%)- and non-insulin-treated (HbA1c 5.6 +/- 0.4%) patients.Conclusions: Type 2 diabetic patients showed no signs of delayed gastric emptying, suggesting that a carbohydrate-rich drink may be safely administrated 180 min before anaesthesia without risk of hyperglycaemia or aspiration pre-operatively.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Nordstrom, CH, et al.
(författare)
-
Bedside interpretation of cerebral energy metabolism utilizing microdialysis in neurosurgical and general intensive care
- 2022
-
Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 13, s. 968288-
-
Tidskriftsartikel (refereegranskat)abstract
- The microdialysis technique was initially developed for monitoring neurotransmitters in animals. In 1995 the technique was adopted to clinical use and bedside enzymatic analysis of glucose, pyruvate, lactate, glutamate and glycerol. Under clinical conditions microdialysis has also been used for studying cytokines, protein biomarkers, multiplex proteomic and metabolomic analyses as well as for pharmacokinetic studies and evaluation of blood-brain barrier function. This review focuses on the variables directly related to cerebral energy metabolism and the possibilities and limitations of microdialysis during routine neurosurgical and general intensive care. Our knowledge of cerebral energy metabolism is to a large extent based on animal experiments performed more than 40 years ago. However, the different biochemical information obtained from various techniques should be recognized. The basic animal studies analyzed brain tissue homogenates while the microdialysis technique reflects the variables in a narrow zone of interstitial fluid surrounding the probe. Besides the difference of the volume investigated, the levels of the biochemical variables differ in different compartments. During bedside microdialysis cerebral energy metabolism is primarily reflected in measured levels of glucose, lactate and pyruvate and the lactate to pyruvate (LP) ratio. The LP ratio reflects cytoplasmatic redox-state which increases instantaneously during insufficient aerobic energy metabolism. Cerebral ischemia is characterized by a marked increase in intracerebral LP ratio at simultaneous decreases in intracerebral levels of pyruvate and glucose. Mitochondrial dysfunction is characterized by a moderate increase in LP ratio at a very marked increase in cerebral lactate and normal or elevated levels of pyruvate and glucose. The patterns are of importance in particular for interpretations in transient cerebral ischemia. A new technique for evaluating global cerebral energy metabolism by microdialysis of the draining cerebral venous blood is discussed. In experimental studies it has been shown that pronounced global cerebral ischemia is reflected in venous cerebral blood. Jugular bulb microdialysis has been investigated in patients suffering from subarachnoid hemorrhage, during cardiopulmonary bypass and resuscitation after out of hospital cardiac arrest. Preliminary results indicate that the new technique may give valuable information of cerebral energy metabolism in clinical conditions when insertion of an intracerebral catheter is contraindicated.
|
|
| 17. |
- Pham, U, et al.
(författare)
-
Personality changes after deep brain stimulation in Parkinson's disease
- 2015
-
Ingår i: Parkinson's disease. - : Hindawi Limited. - 2090-8083 .- 2042-0080. ; 2015, s. 490507-
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson’s disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients.Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported.Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P=0.006;P=0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P=0.027).Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity.
|
|
| 18. |
- Rank, CU, et al.
(författare)
-
Asparaginase-Associated Pancreatitis in ALL: Results from the NOPHO ALL2008 Treatment of Patients 1-45 Years
- 2019
-
Ingår i: Blood. 134 (Suppl. 1), 3820.. - : American Society of Hematology. - 0006-4971 .- 1528-0020.
-
Konferensbidrag (refereegranskat)abstract
- Premature discontinuation of asparaginase reduces cure rate in contemporary acute lymphoblastic leukemia (ALL) treatment. One of the commonest causes of asparaginase truncation is asparaginase-associated pancreatitis (AAP). We prospectively registered AAP during treatment of 2,448 consecutive Nordic/Baltic ALL patients aged 1.0-45.9 years treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (7/2008-10/2018). The Day 280 cumulative incidence of first-time AAP (including 99% (167/168) of AAP events at this time point) was 8.3% (95% confidence interval (CI) 7.0-9.9) with a median time of 104 days (interquartile range (IQR) 70-145) from ALL diagnosis to AAP, with a median of 10 days (IQR 6-13) from last asparaginase exposure, and after a median number of five asparaginase doses (IQR 3-7, max 14 doses). All patients received polyethylene glycol conjugated Escherichia coli-derived asparaginase as standard treatment. Eighty-five percent (140/164, unknown in N=4) of AAP events were severe (AAP-associated symptoms and/or pancreatic enzymes >3x upper normal limit lasting >72 hours or with hemorrhagic pancreatitis, pancreatic abscess, or pseudocyst). Four age groups were defined: 1.0-4.9, 5.0-8.9, 9.0-16.9, and 17.0-45.9 years-each containing approximately 25% of the AAP events. Compared with patients aged 1.0-4.9 years, adjusted (sex, immunophenotype, and white blood cell count) hazard ratios (HR) of AAP were associated with higher age (5.0-8.9 years: HR 2.3, 95% CI 1.5-3.6, P<.0001; 9.0-16.9 years: HR 2.5, 95% CI 1.6-3.8, P<.0001; and 17.0-45.9 years: HR 2.5, 95% CI 1.6-3.8, P<.0001). When analyzing the odds of developing any AAP-related complication among patients with ≥100 days of follow-up after the AAP diagnosis, older children (≥5.0 years) and adolescents had increased odds of developing any complication compared with younger children aged 1.0-4.9 years, notably a more than six-fold increase among adolescents (5.0-8.9 years: odds ratio (OR) 2.67, 95% CI 1.07-6.68, P=.04 and 9.0-16.9 years: OR 6.52, 95% CI 2.35-18.1, P=.0003)-including acute and permanent insulin need; intensive care unit admission; pancreatic pseudocyst development; recurrent abdominal pain; elevated pancreatic enzymes at last-follow-up; imaging compatible with pancreatitis (pancreatic inflammation/edema/pseudocysts/hemorrhage) at last follow-up; and AAP-related death. Adult age was not associated with development of any AAP-related complication (17.0-45.9 years: OR 2.3, 95% CI 0.9-5.9, P=.07). Three patients aged 8.6, 17.3, and 18.6 years died of first-time AAP within 0-29 days from AAP diagnosis. Of 168 AAP patients, 34 (20%) were re-challenged with asparaginase. Fifty percent (17/34) developed a second episode of AAP-41% being severe (7/17). The median time to a second AAP event from asparaginase re-exposure was 29 days (IQR 16-94) and occurred after a median of two asparaginase doses (range 0-7). Neither age group nor severity of the first AAP was associated with increased hazard of a second AAP event. None of the patients with a second AAP were further re-exposed to asparaginase, and none died of the second AAP. Among a total of 196 ALL relapses, 21 patients have had AAP including 17 patients with asparaginase truncation. However, the hazard of relapse (age- and sex-adjusted) was not increased among AAP patients with asparaginase truncation versus AAP patients with asparaginase re-exposure (5.0-year cumulative incidence of relapse: 13.2% versus 14.2%) (HR 1.0, 95% CI 0.3-3.1, P=1.0). When analyzing time to relapse among AAP patients versus non-AAP patients, no difference in hazard of relapse was found (HR 2.0, 95% CI 0.8-4.9, P=.2). In conclusion, adolescents and young adults tolerated asparaginase treatment as well as children; however, the risk of AAP was higher for patients older than 5.0 years of age with no difference with increasing age. Despite a low AAP-related mortality, the morbidity was considerable and most profound for patients aged 9.0-16.9 years. Since asparaginase re-exposure was associated with a high risk of a second AAP event and neither AAP development nor AAP-related asparaginase truncation was associated with increased relapse risk, asparaginase re-exposure should be attempted only in patients with a high risk of leukemic relapse. Finally, there is an unmet need for preventive strategies toward AAP
|
|
| 19. |
- Rank, Cecilie U., et al.
(författare)
-
Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age
- 2020
-
Ingår i: Journal of Clinical Oncology. - Alexandria : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 38:2, s. 145-154
-
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.
|
|
| 20. |
|
|
| 21. |
|
|
