Impact of letermovir on Cytomegalovirus-specific T-cells reconstitution after allogeneic hematopoietic stem cell transplantation in the post-transplant cyclophosphamide era.

Not available.

Biomarkers for an early diagnosis of immune effector cell associated-hemophagocytic syndrome.

Hemophagocytic lymphohistiocytosis (HLH) is a hyper-inflammatory syndrome characterized by deficient NK-cell activity, cytokine storm and altered T-cell immunity, potentially sustained by multiple triggers. Recently, a hyperinflammatory condition resembling HLH has emerged as a potential complication of CAR T-cells. HLH represents a diagnostic conundrum due to its rarity, non-specific presentation and lack of validated biomarkers.

American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel.

Objective: Vacuoles E1 enzyme X-linked autoinflammatory somatic syndrome (VEXAS) is a recently identified rare genetic disorder associated with somatic mutations in the UBA1 gene. VEXAS presents with a combination of inflammatory and hematologic manifestations, leading to increased morbidity and mortality.

Methods: Given the variability in disease presentation and the limited number of studies to date, no clinical documents currently exist to provide guidance to health care providers about the management of VEXAS.

Clonal hematopoiesis meets an autoinflammatory disease: the new paradigm of VEXAS syndrome.

Introduction: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an acquired autoinflammatory disorder caused by somatic mutations in the UBA1 gene. Predominantly affecting males over 50, the disease presents with systemic inflammation, hematologic abnormalities, and features of clonal hematopoiesis, with nearly half of patients developing myelodysplastic syndromes (MDS). The interaction between inflammation and clonal expansion defines disease progression, emphasizing the need for a comprehensive understanding of its pathogenesis and management.

Unmet Needs and Their Impact on Quality of Life and Symptoms in Myelodysplastic Neoplasm Patients and Caregivers.

Background/objectives: The aim of this study was to assess the unmet needs of myelodysplastic neoplasm (MDS) patients and their caregivers, focusing on how these needs impact quality of life (QoL) and daily functioning. MDS predominantly affects older adults. It is often complicated by severe red blood cell transfusion-dependent anemia and may require frequent hospital visits, conferring a substantial burden on patients and caregivers.

Mechanisms of hematopoietic clonal dominance in VEXAS syndrome.

Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers and common nonmalignant disorders. VEXAS syndrome is a recently discovered, adult-onset, autoinflammatory disease burdened by a high mortality rate and caused by dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms driving clonal dominance are unknown.

Methodology and clinical utility of longitudinal UBA1 tracking in VEXAS syndrome.

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.

Sorafenib maintenance in FLT3-ITD mutated AML after allogeneic HCT: a real-world, single-center experience.

Despite allogeneic hematopoietic stem cell transplant (allo-HCT) and the development of novel FLT3 inhibitors in both induction (midostaurin) and in the relapsed/refractory setting (gilteritinib), FLT3-ITD mutated leukemia (FLT3-ITD+ AML) still represents a challenge for modern hematology. Sorafenib is, to this date, the only inhibitor that demonstrated efficacy in improving both progression-free and overall survival as post-HCT maintenance therapy, even if its use in this setting has not been approved so far by regulatory agencies. The aim of our study was to evaluate the feasibility, safety, and efficacy of sorafenib maintenance in preventing early relapse in FLT3-ITD+ AML after HCT in a single-center experience.

Spontaneous remission of choroidal involvement by chronic myelomonocytic leukemia: a case report.

Chronic myelomonocytic leukemia (CMML) is a rare hematological disorder characterized by variable risk of evolution to acute myeloid leukemia; to date, allogeneic stem cell transplantation is the only curative treatment. We report a case of choroidal involvement in a woman affected by CMML and presenting only with visual impairment. The patient was initially evaluated for an intensive therapeutic approach, but after biopsy the ocular lesion spontaneously regressed.

Case report: Cytopenias in VEXAS syndrome - a WHO 2022 based approach in a single-center cohort.

VEXAS syndrome is an acquired autoinflammatory disease characterized in most cases by cytopenias and macrocytic anemia. Dyshematopoiesis is a frequent finding in chronic inflammatory conditions and therefore, cytopenias are not easily classified in VEXAS patients. Here we report a series of 7 patients affected by VEXAS associated cytopenias, treated at our center.

Dynamics of polyclonal immuno-reconstitution after allogeneic transplant with post-transplant cyclophosphamide and letermovir.

Cytomegalovirus (CMV) reactivations are strong stimulators of immune-reconstitution (IR) in hematopoietic stem cell transplantation (HSCT) recipients. Herein, we analyzed 317 CMV-seropositive consecutive patients (n = 109 letermovir, LTV; n = 208 no-LTV), undergoing HSCT with post-transplant cyclophosphamide (PTCy) and calcineurin inhibitor- (CNI) free graft-versus-host-disease (GvHD) prophylaxis. At day+90, median CD19/mm was higher in LTV-cohort: 5.

Case Report: Favorable outcome of allogeneic hematopoietic stem cell transplantation in SARSCoV2 positive recipient, risk-benefit balance between infection and leukemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in SARS-CoV-2 positive candidates is usually delayed until the clinical resolution of the infection's symptoms and a negative nasopharyngeal molecular test. However, prolonged SARS-CoV-2 positivity has been frequently observed in haematological malignancies, thus representing a challenge for the timing of transplant procedures. Here, we report on the case of a 34-year-old patient with recent pauci-symptomatic COVID-19 undergoing transplant for high-risk acute B-lymphoblastic leukemia before achieving viral clearance.

[Role of allogeneic hematopoietic cell transplantation after anti-CD19 CAR T-cell treatment: Guidelines from the SFGM-TC].

The role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR T- treatment cells in hematologic malignancies is currently controversial. Prolonged remissions after several years of follow-up suggest that there is a curative effect of CAR T-cells therapy, whereas allo-HCT was previously considered the only curative treatment in relapse situation. The aim of this harmonization workshop is to detail the existing data in the literature on the feasibility of allo-HCT after CAR T-cells and to propose to consider allograft in selected patients with B-acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL).

SARS-COV-2 screening in allogeneic hematopoietic stem cell donors: Implications for the evaluation process and eligibility.

Introduction: Soon after the onset of the SARS-CoV-2 pandemic, viral screening by nasopharyngeal swab became mandatory for allogeneic hematopoietic stem cell (HSC) donor eligibility.

Methods: We described our monocenter experience with allogeneic HSC donors from February 1 to the October 31, 2020 to verify whether the introduction of SARS-CoV-2 screening altered the donor eligibility and/or entailed a prolongation of the evaluation process.

Results: A total of 21 allogeneic HSC donors were screened during the above-mentioned period upon request by the local transplant physicians or by the Italian Bone Marrow Donor Registry; among the HSC donors ( = 17) who completed the eligibility process and further received the nasopharyngeal swab, all but one were negative for the presence of SARS-CoV-2.

Heterogeneity of the bone marrow niche in patients with myeloproliferative neoplasms: ActivinA secretion by mesenchymal stromal cells correlates with the degree of marrow fibrosis.

Mesenchymal stromal cells (MSCs) represent an essential component of the bone marrow (BM) niche and display disease-specific alterations in several myeloid malignancies. The aim of this work was to study possible MSC abnormalities in Philadelphia-negative myeloproliferative neoplasms (MPNs) in relationship to the degree of BM fibrosis. MSCs were isolated from BM of 6 healthy donors (HD) and of 23 MPN patients, classified in 3 groups according to the diagnosis and the grade of BM fibrosis: polycythemia vera and essential thrombocythemia (PV/ET), low fibrosis myelofibrosis (LF-MF), and high fibrosis MF (HF-MF).

Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Era of Tyrosine Kinase Inhibitors: A Registry-Based Study of the Italian Blood and Marrow Transplantation Society (GITMO).

We performed a nationwide registry-based analysis to describe the clinical outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL) who underwent an allogeneic hematopoietic stem cell transplantation (HSCT) after a tyrosine kinase inhibitor (TKI)-based treatment A total of 441 patients were included in the study. The median age at HSCT was 44 years (range, 18 to 70 years). All 441 patients (100%) received TKI before HSCT (performed between 2005 and 2016).