Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is a haemato-inflammatory syndrome genetically defined by somatic mutations in the X-linked UBA1 gene, typically Val/Thr/Leu substitutions at the Met41 hotspot. Clinical manifestations are heterogeneous and refractory to most haemato-rheumatological treatments. To date, no guidelines exist for the management of VEXAS, and scarce is the evidence on methodology and clinical significance of longitudinal UBA1 clonal burden evaluation upon therapy.
View Article and Find Full Text PDFCurr Res Transl Med
October 2024
Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded.
View Article and Find Full Text PDFWith ongoing global warming, increasing water deficits promote physiological stress on forest ecosystems with negative impacts on tree growth, vitality, and survival. How individual tree species will react to increased drought stress is therefore a key research question to address for carbon accounting and the development of climate change mitigation strategies. Recent tree-ring studies have shown that trees at higher latitudes will benefit from warmer temperatures, yet this is likely highly species-dependent and less well-known for more temperate tree species.
View Article and Find Full Text PDFSince the early description of three patients with relapsed leukaemia after allogeneic haematopoietic cell transplantation (HCT) who obtained complete remission after donor lymphocyte infusions (DLIs), the added value of this procedure to induce or maintain graft-versus-leukaemia immunity has been undisputed. For more than 30 years, DLIs have become common practice as prophylactic, pre-emptive, or therapeutic immunotherapy. However, as with many aspects of allogeneic HCT, centres have developed their own routines and practices, and many questions related to the optimal applications and toxicity, or to the immunobiology of DLI induced tumour-immunity, remain.
View Article and Find Full Text PDFTree mortality and forest dieback episodes are increasing due to drought and heat stress. Nevertheless, a comprehensive understanding of mechanisms enabling trees to withstand and survive droughts remains lacking. Our study investigated basal area increment (BAI), and δC-derived intrinsic water-use-efficiency (WUE), to elucidate beech resilience across four healthy stands in Italy with varying climates and soil water availability.
View Article and Find Full Text PDFSystemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia (MCL) and SM with an associated hematologic neoplasm (SM-AHN), the latter accounting for 60-70% of all AdvSM cases. Detection of a disease-triggering mutation in the KIT gene (esp.
View Article and Find Full Text PDFInvestigating the evaluation of eligibility for transplant in myelofibrosis (MF): The role of HCT-CI and BMI. HCT-CI emerges as a key prognostic factor, while BMI shows limited impact. This study expands insights for better clinical decision-making in MF allo-HCT.
View Article and Find Full Text PDFClimate change significantly impacts global forests, leading to tree decline and dieback. To cope with climate change, trees develop several functional traits, such as intra-annual density fluctuations (IADFs) in tree rings. The formation of these traits facilitates trees to optimize resource allocation, allowing them to withstand periods of stress and eventually recover when the conditions become favourable again.
View Article and Find Full Text PDFIn highly climate-change-sensitive regions, such as the Mediterranean, increasing knowledge of climate-driven growth dynamics is required for habitat conservation and forecasting species adaptability under future climate change. In this study, we test a high spectrum of climatic signals, not only monthly and seasonal but also on a multi-year scale and include the single tree analysis to answer this issue, focusing on a low-elevation thermophilic old-growth beech forest surrounding the Bracciano Lake in Central Italy. Through a dendroecological and isotope analysis, we evaluate both short- and long-term sensitivity of F.
View Article and Find Full Text PDFTransplant Cell Ther
January 2024
Total body irradiation (TBI) at myeloablative doses is superior to chemotherapy-based regimens in young patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, in elderly and unfit patients, in whom reduced-intensity conditioning (RIC) regimens are preferred, whether a TBI-based or a chemotherapy-based approach is better is unexplored. Thiotepa can be used as part of ALL conditioning regimens.
View Article and Find Full Text PDFAllogeneic hematopoietic cell transplantation (allo-HCT) is curative for myelofibrosis (MF) but assessing risk-benefit in individual patients is challenging. This complexity is amplified in CALR-mutated MF patients, as they live longer with conventional treatments compared to other molecular subtypes. We analyzed outcomes of 346 CALR-mutated MF patients who underwent allo-HCT in 123 EBMT centers between 2005 and 2019.
View Article and Find Full Text PDFIntra-Annual Density Fluctuations (IADFs) are an important wood functional trait that determine trees' ability to adapt to climatic changes. Here, we use a large tree-ring database of 11 species from 89 sites across eight European countries, covering a climatic gradient from the Mediterranean to northern Europe, to analyze how climate variations drive IADF formation. We found that IADF occurrence increases nonlinearly with ring width in both gymnosperms and angiosperms and decreases with altitude and age.
View Article and Find Full Text PDFThe use of haploidentical hematopoietic cell transplantation (haplo-HCT) with peripheral blood stem cells (PBSCs) to treat acute myelogenous leukemia (AML) is increasing. We explored whether the addition of antithymocyte globulin (ATG) to post-transplantation cyclophosphamide (PTCy) allows better outcomes compared with PTCy alone in haplo-HCT with PBSCs (haplo-PBSCT). We included 441 adult patients undergoing a first haplo-PBSCT for AML in first or second complete remission; graft-versus-host disease (GVHD) prophylaxis contained either PTCy alone (n = 374) or ATG plus PTCy (n = 67), in addition to cyclosporine A (CsA) and mycophenolate mofetil (MMF) as other immunosuppressive agents.
View Article and Find Full Text PDFWe evaluated prognostic factors in 83 intensively treated adult patients with mutated AML. Targeted next-generation sequencing revealed high frequency of co-mutations in epigenetic modifiers or proliferation pathways. minimal residual disease (MRD), assessed in bone marrow by specific polymerase chain reaction after one chemotherapy course, was >0.
View Article and Find Full Text PDFThe mechanistic pathways connecting ocean-atmosphere variability and terrestrial productivity are well-established theoretically, but remain challenging to quantify empirically. Such quantification will greatly improve the assessment and prediction of changes in terrestrial carbon sequestration in response to dynamically induced climatic extremes. The jet stream latitude (JSL) over the North Atlantic-European domain provides a synthetic and robust physical framework that integrates climate variability not accounted for by atmospheric circulation patterns alone.
View Article and Find Full Text PDFWhether to choose Haploidentical (Haplo) or one-antigen mismatched unrelated donor (1Ag-MMUD) hematopoietic cell transplantation (HCT) with post-transplant cyclophosphamide (PTCy) remains an unanswered question. We compared PTCy- Haplo-HCT to PTCy-1Ag-MMUD-HCT for acute myeloid leukemia (AML) in complete remission (three groups: 1Ag-MMUD using peripheral blood (1Ag-MMUD-PB; n = 155); Haplo using bone marrow (Haplo-BM; n = 647) or peripheral blood (Haplo-PB; n = 949)). Haplo-BM and Haplo-PB had a higher non-relapse mortality (NRM) compared to 1Ag-MMUD-PB (HR 2.
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