Epigenetic aging of human blood cells is influenced by the age of the host body.

Allogenic hematopoietic stem cell transplantation is a therapeutic procedure performed over a wide range of donor and recipient age combinations, representing natural experiments of how the age of the recipient affects aging in transplanted donor cells in vivo. We measured DNA methylation and epigenetic aging in donors and recipients and found that biological epigenetic clocks are accelerated in cells transplanted into an older body and decelerated in a younger body. This is the first evidence that the age of the circulating environment influences human epigenetic aging in vivo.

Allogeneic stem cell transplant recipients surviving at least 2 years without relapse: outcome and risk factors.

Outcomes of 2-year survivours undergoing allo-haematopoietic stem cell transplantation at Oslo University Hospital were retrospectively assessed with the objectives of identification of risk factors for late death as possible means for precautionary measures and interventions to improve long-term survival. 421 patients with haematological malignancy, transplanted between 2005 and 2019, alive and free of disease after 2 years were included with data reported from The OUS-HSCT registry. Median follow-up was 6.2 years (2.016.1), and 232 patients (55%) were observed for minimum 5 years. The probability of being alive 5 and 10 years after HSCT was 86% and 76%. Primary risk factors for late death included initial diagnosis of age ≥ 60 years, chronic lymphocytic leukaemia (CLL), previous blood stream- or invasive fungal infection (BSI, IFI), and chronic graft-versus-host disease (cGVHD). Transplant-related mortality (TRM) and relapse at 5 years were 9.0% and 7.7%, respectively. Two factors were associated with the latter: cytomegalovirus (CMV) seronegative donor and CLL. Compared with the age- and gender-matched Norwegian general population, life expectancy was lower for each disease, except for CML. The prospect for the long-term survival is good for 2-year survivors of the allogeneic hematopoietic stem cell transplantation. However, life expectancy remains inferior to the age- and gender-matched general population. Optimising prophylaxis and treatment for chronic GVHD, BSI and IFI are needed along with the improved adherence to guidelines for early detection of secondary malignancies. Measures to improve immune reconstitution, possibly the microbiota, and the use of CMV seropositive donors regardless of recipient sero-status may be warranted and should be addressed in further studies.

Chronic neutropenia in adults. / Kronisk nøytropeni hos voksne.

Neutrophils are an important component of the innate immune system, and they prevent bacterial and fungal infections by phagocytosis and killing of pathogens. Neutropenia is defined as an abnormally low number of circulating neutrophils, and the term chronic neutropenia is used when it lasts more than three months. The objective of this clinical review is to raise awareness among doctors in Norway of chronic neutropenia and possible causes. A patient with severe neutropenia and fever requires immediate admission to hospital and initiation of empiric sepsis treatment before the cause of neutropenia has been determined, but patients with chronic neutropenia do not always require rapid and extensive workup.

Extracorporeal Photopheresis as Graft-versus-Host Disease Prophylaxis: A Randomized Controlled Trial.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the sole curative option for many patients diagnosed with hematologic malignancies. A major obstacle is graft-versus-host disease (GVHD), causing significant morbidity and mortality. Extracorporeal photopheresis (ECP) is an increasingly applied treatment for GVHD, owing in part to its favorable safety profile. In contrast, reports on the use of ECP to prevent GVHD are rare, and randomized controlled trials (RCTs) are lacking. We conducted an RCT to assess whether ECP applied post-transplantation could prevent the development of GVHD within the first year of transplantation. We enrolled 157 patients (age 18 to 74 years) with a hematologic malignancy undergoing their first allo-HSCT, randomized as 76 to the intervention group and 81 to the control group. ECP was initiated directly on engraftment and was planned twice weekly for 2 weeks, then once weekly for 4 weeks. GVHD, relapse, and death were analyzed by Cox regression analysis. During the first year, 45 patients in the intervention group and 52 control patients developed GVHD (hazard ratio [HR], .82; 95% confidence interval [CI], .55 to 1.22; P = .32). There were no differences in acute or chronic GVHD or its organ distribution in this intention-to-treat RCT. A per-protocol analysis revealed a significant difference in GVHD between the intervention group (per-protocol; n = 39 of 76) and the control group (n = 77), 46% versus 68%, respectively (HR, .47; 95% CI, .27 to .80; P = .006). Relapse occurred in 15 patients in the intervention group and in 11 control patients (HR, 1.38; 95% CI, .64 to 3.01; P = .42). GVHD-free relapse-free survival, event-free survival, overall survival, and nonrelapse mortality did not differ significantly between the 2 study groups. There also was no significant difference in immune reconstitution between the 2 groups. This first intention-to-treat RCT investigating ECP as GVHD prophylaxis in allo-HSCT for hematologic malignancy does not support the use of ECP as an adjunct to standard drug-based GVHD prophylaxis.

A man in his sixties with chondritis and bone marrow failure. / En mann i 60-årene med kondritt og benmargssvikt.

BACKGROUND: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) first described in 2020, is caused by a limited repertoire of somatic mutations in UBA1, a gene involved in the initiation of ubiquitination. Ubiquitination, adding an ubiquitin protein to a substrate protein, can have various effects on the substrate. Disruption of UBA1 function results in diverse clinical manifestations, mimicking a variety of disorders. CASE PRESENTATION: A man in his sixties presented with fever, chest pain, fatigue, pulmonary infiltrates and elevated acute phase reactants. Initially he was thought to have extra-cranial giant cell arteritis. When he developed ear and nose chondritis, a revised diagnosis of relapsing polychondritis was made. Subsequently he developed macrocytic anaemia and thrombocytopenia. His condition remained resistant to medical therapy and he died eight years after disease onset. Analysis of stored DNA revealed a somatic mutation in UBA1 confirming the diagnosis of VEXAS syndrome. INTERPRETATION: VEXAS syndrome is a newly identified inflammatory disorder due to an acquired mutation in haematopoietic bone marrow cells in older men. The syndrome may be misdiagnosed as treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome or giant cell arteritis. We describe the first individual with molecularly confirmed VEXAS syndrome in Norway.

Superior Graft-versus-Host Disease-Free Relapse-Free Survival in Matched Unrelated Donor Hematopoietic Stem Cell Transplantation with Anti-Thymocyte Globulin (ATG) Compared to Matched Related Donor without ATG.

The use of anti-T cell globulin (ATG) in allogeneic stem cell transplantation with matched unrelated donors (MUDs) is considered standard of care in many transplant centers, as these patients are at higher risk of developing acute and chronic graft-versus-host disease (GVHD). Several publications have reported reduced incidence of chronic GVHD compared to matched related donors (MRDs). This may support the idea of introducing ATG in prospective clinical trials, also in MRDs, in an effort to reduce the long-term complications with moderate and severe GVHD. We retrospectively analyzed 169 patients, in whom ATG was given to patients who underwent transplantation with MUDs (n = 124) and not MRDs (n = 45). The incidence acute GVHD II to IV and III to IV was significantly lower in the MUD group compared to the MRD group (28.2% versus 51.3% and 8.1% versus 24.7%). Extensive chronic GVHD incidence was 5% versus 40%. Our results further support the rationale for examining the efficacy of ATG in MRDs in prospective randomized trials.