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- Remberger, Mats, et al.
(författare)
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The CD34+ Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors
- 2020
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Ingår i: Clinical Hematology International. - : Springer Science and Business Media LLC. - 2590-0048. ; 2:2, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34+ cell dose was 5.6 × 106/kg (0.6–17.0). In the multivariate analysis, a CD34 cell dose of 6–7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 106/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 106/kg) correlated with less acute GVHD (aGVHD) II–IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.
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- Ali, M. M., et al.
(författare)
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Addition of Anti-thymocyte Globulin in Allogeneic Stem Cell Transplantation With Peripheral Stem Cells From Matched Unrelated Donors Improves Graft-Versus-Host Disease and Relapse Free Survival
- 2021
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Ingår i: Clinical Lymphoma, Myeloma & Leukemia. - : Elsevier. - 2152-2650 .- 2152-2669. ; 21:9, s. 598-605
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Tidskriftsartikel (refereegranskat)abstract
- In 2014 we introduced anti-thymocyte globulin (ATG) to the graft-versus-host disease (GvHD) prophylaxis regimen in allogeneic stem cell transplantation (Allo-HSCT) with peripheral stem cells (PBSC) from matched unrelated donors (MUD). We analysed the outcomes of 415 patients who went through MUD alto-HSCT and received PBSC with or without ATG. We report dramatic reduction of the incidence of chronic GvHD and our study illustrates the benefit of ATG in addition to standard GvHD prophylaxis. Anti-thymocyte globulin (ATG) is commonly used to prevent graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To evaluate the impact of ATG as part of the GvHD prophylaxis in our institution, we report the outcome of 415 patients with matched unrelated donors (MUD) transplanted for hemato-logical malignancies with or without ATG from 2005 to 2019 at Oslo University Hospital, Norway. The following groups were compared: (1) 154 patients transplanted with peripheral blood stem cells (PBSC) without ATG 2005-2014. (2) 137 patients transplanted with bone marrow stem cells (BMSC) 2005-2019. (3) 124 patients transplanted with PBSC and ATG (PBSC + ATG) 2014-2019. Three years survival was similar in the groups, 61% following allografting with PBSC, 54% with BMSC, and 59% with PBSC + ATG. Acute GvHD grade III-IV was 14%, 14%, and 7%; chronic GvHD was 81%, 32, and 26%; and extensive cGvHD 44%, 15%, and 6% in the corresponding groups. Both acute and chronic GvHD were significantly reduced in the PBSC + ATG-versus the PBSC group (p < 0.05 and p < 0.001 respectively).Transplant-related mortality (TRM) was 33%, 25%, and 17% (p = 0.18). Graft versus host disease and relapse free survival (GRFS) at 3 years was 43 %, 43%, and 64% in the groups. Adding ATG to the GvHD prophylaxis regimen of MUD allo-HSCT with PBSC resulted in a substantial reduction of both acute and chronic GvHD without compromising the disease control, reflected in a superior 3 years GRFS.
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- Sallee, J. B., et al.
(författare)
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Southern ocean carbon and heat impact on climate
- 2023
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Ingår i: Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. - 1364-503X .- 1471-2962. ; 381:2249
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Tidskriftsartikel (refereegranskat)abstract
- The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate.This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.
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- Silvano, Alessandro, et al.
(författare)
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Observing Antarctic Bottom Water in the Southern Ocean
- 2023
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Ingår i: Frontiers in Marine Science. - 2296-7745. ; 10
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Forskningsöversikt (refereegranskat)abstract
- Dense, cold waters formed on Antarctic continental shelves descend along the Antarctic continental margin, where they mix with other Southern Ocean waters to form Antarctic Bottom Water (AABW). AABW then spreads into the deepest parts of all major ocean basins, isolating heat and carbon from the atmosphere for centuries. Despite AABW's key role in regulating Earth's climate on long time scales and in recording Southern Ocean conditions, AABW remains poorly observed. This lack of observational data is mostly due to two factors. First, AABW originates on the Antarctic continental shelf and slope where in situ measurements are limited and ocean observations by satellites are hampered by persistent sea ice cover and long periods of darkness in winter. Second, north of the Antarctic continental slope, AABW is found below approximately 2 km depth, where in situ observations are also scarce and satellites cannot provide direct measurements. Here, we review progress made during the past decades in observing AABW. We describe 1) long-term monitoring obtained by moorings, by ship-based surveys, and beneath ice shelves through bore holes; 2) the recent development of autonomous observing tools in coastal Antarctic and deep ocean systems; and 3) alternative approaches including data assimilation models and satellite-derived proxies. The variety of approaches is beginning to transform our understanding of AABW, including its formation processes, temporal variability, and contribution to the lower limb of the global ocean meridional overturning circulation. In particular, these observations highlight the key role played by winds, sea ice, and the Antarctic Ice Sheet in AABW-related processes. We conclude by discussing future avenues for observing and understanding AABW, impressing the need for a sustained and coordinated observing system.
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- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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- Weum Abrahamsen, I, et al.
(författare)
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Posttransplantation Lymphoproliferative Disease Treated by Retransplantation
- 2020
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Ingår i: Case reports in immunology. - : Hindawi Limited. - 2090-6609 .- 2090-6617. ; 2020, s. 9403123-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Epstein–Barr virus- (EBV-) induced posttransplantation lymphoproliferative disease (PTLD) is a life-threatening complication following allogeneic stem cell transplantation. The main risk factor is anti-thymocyte globulin (ATG). Patients who fail first-line treatment with rituximab have a poor prognosis. Though adoptive transfer of EBV-specific T cells is a potentially effective option, it is not readily available. In this case report, the patient developed PTLD following transplantation for aplastic anemia using ATG as part of the conditioning. He failed rituximab treatment and developed graft failure. We were aware that the stem cell donor had a recent EBV infection prior to transplantation, whereas the patient most likely was EBV negative before transplant. We describe our strategy to meet the patient’s urgent need for EBV-specific T cells, as well as new hematopoietic stem cells. The same donor was used for a second transplant, using peripheral blood stem cells. The conditioning used was thiotepa/busulfan/fludarabin with a single dose of cyclophosphamide after transplant as graft-versus-host disease (GVHD) prophylaxis. The EBV DNA levels fell when conditioning was started, and have been undetectable since day +15 and remained so till 18 months after transplantation. The patient is doing well. This case reports successful use of cyclophosphamide after transplantation as GVHD prophylaxis, preserving virus-specific immunity.
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