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- Khoury, J. D., et al.
(författare)
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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
- 2022
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36, s. 1703-1719
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Tidskriftsartikel (refereegranskat)abstract
- The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
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| 2. |
- Hochhaus, A., et al.
(författare)
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European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia
- 2020
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 34:4, s. 966-984
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Forskningsöversikt (refereegranskat)abstract
- The therapeutic landscape of chronic myeloid leukemia (CML) has profoundly changed over the past 7 years. Most patients with chronic phase (CP) now have a normal life expectancy. Another goal is achieving a stable deep molecular response (DMR) and discontinuing medication for treatment-free remission (TFR). The European LeukemiaNet convened an expert panel to critically evaluate and update the evidence to achieve these goals since its previous recommendations. First-line treatment is a tyrosine kinase inhibitor (TKI; imatinib brand or generic, dasatinib, nilotinib, and bosutinib are available first-line). Generic imatinib is the cost-effective initial treatment in CP. Various contraindications and side-effects of all TKIs should be considered. Patient risk status at diagnosis should be assessed with the new EUTOS long-term survival (ELTS)-score. Monitoring of response should be done by quantitative polymerase chain reaction whenever possible. A change of treatment is recommended when intolerance cannot be ameliorated or when molecular milestones are not reached. Greater than 10% BCR-ABL1 at 3 months indicates treatment failure when confirmed. Allogeneic transplantation continues to be a therapeutic option particularly for advanced phase CML. TKI treatment should be withheld during pregnancy. Treatment discontinuation may be considered in patients with durable DMR with the goal of achieving TFR.
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- Waszczuk-Gajda, A, et al.
(författare)
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Complications of Autologous Stem Cell Transplantation in Multiple Myeloma: Results from the CALM Study
- 2022
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The main goal of this post hoc analysis of the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study was to evaluate the rate of short- and long-term infectious and non-infectious complications occurring after ASCT in patients with multiple myeloma (MM). Methods: The analysis included all patients with MM from the CALM study who underwent ≥1 ASCT. The primary endpoint of the analysis was to determine the rate of infectious and non-infectious complications after ASCT and to compare them in three time periods: 0–100 days, 101 days–1 year, and >1 year after the first transplant. Results: The analysis included a total of 3552 patients followed up for a median of 56.7 months (range 0.4–108.1). Complication rates decreased with the time from ASCT with 24.85 cases per 100 patient-years from day 0 to 100 days after the transplant, and <2.31 cases per 100 patient-years from the 101st day. At 100 days after ASC T, 45.7% of patients had complications, with infectious events being twice as frequent as non-infectious complications. Bacterial infections (6.5 cases per 100 patient-years, 95% CI: 6.1–7.0) and gastrointestinal complications (4.7 cases per 100 patient-years, 95% CI: 4.3–5.1) were the most common early events. The pattern of complications changed with time from ASCT. The presence of complications after ASCT was not associated with overall survival. Conclusions: Our data provide a solid basis for comparing ASCT-related complications to those caused by emerging treatments in multiple myeloma, such as CAR T-cell therapy and other immunotherapies.
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- Crawley, C, et al.
(författare)
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Outcomes of reduced-intensity transplantation for chronic myeloid leukemia : an analysis of prognóstic factors from the Chronic Leukemia Working Party of the EBMT
- 2005
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 106:9, s. 2969-2976
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Tidskriftsartikel (refereegranskat)abstract
- This study reports outcomes of allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning (RIC) in 186 patients with chronic myeloid leukemia (CML) from the European Group for Blood and Marrow Transplantation (EBMT). The median age was 50 years, and 64% were in first chronic phase (CP1), CP2 13%, accelerated phase 17%, and blast crises 6%. The median EBMT transplant score was 3. The day 100 transplantation-related mortality (TRM) was 6.1% (confidence interval [CI], 3.4%-11%) but rose to 23.3% (CI, 14%-27%) at 2 years. Fludarabine, busulfan, and antithymocyte globulin (Fd/Bu/ATG) was associated with the lowest TRM of 11.6% (CI, 4.7%-11%) at 1 year. Acute graft-versus-host disease (GvHD) grade II to IV occurred in 32% and chronic GvHD in 43% (extensive in 24%). ATG was associated with a lower incidence of chronic GvHD (cGvHD). The overall survival (OS) and progression-free survival (PFS) at 3 years were 58% (CI, 50%-66%) and 37% (CI, 30%-45%), respectively. Adverse OS was associated with advanced disease (relative risk [RR], 3.4). PFS was inferior in advanced disease (RR, 2.7) and a trend to improved outcomes with Fd/Bu/ATG (RR, 0.58). RIC allografts are feasible in CML in first or second CP. Since no other RIC regimen demonstrated superiority, Fd/Bu/ATG should be considered as baseline in future prospective trials.
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| 28. |
- Dou, S.X., et al.
(författare)
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Microstructure and flux pinning in superconducting Bi-Pb-Sr-Ca-Cu-O wires
- 1990
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Ingår i: Physica. C, Superconductivity. - 0921-4534 .- 1873-2143. ; 172:1-2, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- The critical current density (Jc) of Ag-clad Bi-Pb-Sr-Ca-Cu-O wire has been measured to be 1.2×104 A/cm2 at 77 K in zero field. The high Jc is attributed to a combination of elimination of the poisoning effect of Ag on superconductivity, grain alignment, and enhancement of flux pinning. Jc-H dependence was significantly improved in the Ag-clad tape, which has a Jc of 1.0×103 A /cm2 at 77 K and 4000 Oe, while the Jc of the sintered pellet drops two orders of magnitude at only 100 Oe. A pronounced anisotropy in Jc under high magnetic field is attributed to the grain alignment. Planar defects, such as heavy stacking faults parallel to the a-b plane in the rolled tape, are considered to be effective pinning centres.
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| 37. |
- Ljungman, P, et al.
(författare)
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COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:10, s. 2885-2894
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Tidskriftsartikel (refereegranskat)abstract
- This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.
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| 43. |
- Wahl, Simone, et al.
(författare)
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Epigenome-wide association study of body mass index, and the adverse outcomes of adiposity
- 2017
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Ingår i: Nature. - : NATURE PUBLISHING GROUP. - 0028-0836 .- 1476-4687. ; 541:7635, s. 81-
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 1.5 billion people worldwide are overweight or affected by obesity, and are at risk of developing type (2) diabetes, cardiovascular disease and related metabolic and inflammatory disturbances(1,2). Although the mechanisms linking adiposity to associated clinical conditions are poorly understood, recent studies suggest that adiposity may influence DNA methylation(3-6), a key regulator of gene expression and molecular phenotype(7). Here we use epigenome-wide association to show that body mass index (BMI; a key measure of adiposity) is associated with widespread changes in DNA methylation (187 genetic loci with P < 1 x 10(-7), range P = 9.2 x 10(-8) to 6.0 x 10(-46); n = 10,261 samples). Genetic association analyses demonstrate that the alterations in DNA methylation are predominantly the consequence of adiposity, rather than the cause. We find that methylation loci are enriched for functional genomic features in multiple tissues (P < 0.05), and show that sentinel methylation markers identify gene expression signatures at 38 loci (P < 9.0 x 10(-6), range P = 5.5 x 10(-6) to 6.1 x 10(-35), n = 1,785 samples). The methylation loci identify genes involved in lipid and lipoprotein metabolism, substrate transport and inflammatory pathways. Finally, we show that the disturbances in DNA methylation predict future development of type 2 diabetes (relative risk per 1 standard deviation increase in methylation risk score: 2.3 (2.07-2.56); P = 1.1 x 10(-54)). Our results provide new insights into the biologic pathways influenced by adiposity, and may enable development of new strategies for prediction and prevention of type 2 diabetes and other adverse clinical consequences of obesity.
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| 49. |
- Cordonnier, Catherine, et al.
(författare)
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Immune response to the 23-valent polysaccharide pneumococcal vaccine after the 7-valent conjugate vaccine in allogeneic stem cell transplant recipients : Results from the EBMT IDWP01 trial
- 2010
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:15, s. 2730-2734
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Tidskriftsartikel (refereegranskat)abstract
- The current recommendations for active immunization after stem cell transplant (SCT) include 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7) from 3 months after transplant, followed by a 23-valent polysaccharide pneumococcal vaccine (PPV23). However, until now, the immune response to PPV23 after PCV7 has not been assessed after SCT. In the EBMT IDWP01 trial, 101 patients received 1 dose of PPV23 at 12 or 18 months, both after 3 doses of PCV7. The efficacy of PPV23 was assessed 1 month later and at 24 months after transplant by the pneumococcal serotype 1 and 5 antibody levels. Serotype 1 and 5 are not included in PCV7. Although the geometric mean concentrations were significantly higher 1 month after PPV23, for both antigens, the response rates (>= 0.15 mu g/mL), in the range of 68-94%, were not different between groups independent of the assessment date. One PPV23 dose after 3 PCV7 doses, already known to increase the response to PCV7, also extends the serotype coverage given 12 or 18 months after transplant. (C) 2010 Elsevier Ltd. All rights reserved.
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| 50. |
- Cordonnier, Catherine, et al.
(författare)
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Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation
- 2009
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 48:10, s. 1392-1401
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after transplantation. METHODS: We performed a multicenter, randomized, noninferiority study involving 158 patients from 13 European Group for Blood and Marrow Transplantation centers who were randomly allocated at approximately 100 days after myeloablative stem cell transplantation to receive a series of vaccinations (3 doses of PCV7 given 1 month apart) that was started immediately (i.e., 3 months after transplantation) or 6 months later (i.e., 9 months after transplantation). The primary evaluation criterion was the rate of response (antibody level, > or = 0.15 microg/mL for each of the 7 serotypes) at 1 month after the third dose of PCV7. The noninferiority margin was 20%. All patients were followed up for 24 months after transplantation or until death, whichever occurred first. RESULTS: We found that the response rate was not lower after early vaccination (79% [45 of 57 patients]) than after late vaccination (82% [47 of 57 patients]) (difference, -3.5%; 90% confidence interval, -15.6 to 8.6; not significant). CONCLUSIONS: We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.
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