A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice.

Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates.

Combination Treatment of Resistant Acute Promyelocytic Leukemia Cells with Arsenic Trioxide and Anti-Apoptotic Gene Inhibitors.

Background: Arsenic trioxide (ATO) is an anticancer agent for treating acute promyelocytic leukemia (APL). However, 5-10% of patients fail to respond, developing relapsed/refractory disease. The aim of this study was to identify potential new therapeutic approaches for ATO-unresponsive APL by targeting the anti-apoptotic genes that contribute to drug resistance.

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.

Response Rates and Transplantation Impact in Patients with Relapsed Acute Promyelocytic Leukemia.

Background: The introduction of all- retinoic acid (ATRA) and arsenic trioxide (ATO) has radically improved the prognosis of acute promyelocytic leukemia (APL), with cure rates above 80%. While relapse occurs in less than 20% of cases, addressing this issue remains challenging. Identifying effective salvage therapies for relapsed APL is crucial to improve patient outcomes.

Evolution of transcriptomic profiles in relapsed inv(16) acute myeloid leukemia.

Acute myeloid leukemia (AML) with inv(16) is typically associated with a favourable prognosis. However, up to 40 % of patients will eventually experience disease relapse. Herein, we dissected the genomic and transcriptomic profile of inv(16) AML to identify potential prognostic markers and therapeutic vulnerabilities.

The role of clonal progression leading to the development of therapy-related myeloid neoplasms.

Therapy-related myeloid neoplasms (t-MN) are characterized by aggressive features and a dismal prognosis. Recent evidence suggests a higher incidence of t-MN in individuals harboring clonal hematopoiesis of indeterminate potential (CHIP). In order to gain insight into CHIP-driven malignant progression, we gathered data from ten published reports with available detailed patient characteristics at the time of primary malignancy and t-MN development.

Financial toxicity and health-related quality of life in long-term survivors of acute promyelocytic leukaemia.

Objectives: We aimed to investigate the association between financial toxicity (FT) and the health-related quality of life profile of long-term survivors of acute promyelocytic leukaemia (APL) treated within a universal healthcare system.

Methods: We evaluated FT using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We also compared the prevalence of clinically important problems and symptoms between the survivors of APL with or without FT, using evidence-based thresholds for the EORTC QLQ-C30.

Unlocking the potential of synthetic patients for accelerating clinical trials: Results of the first GIMEMA experience on acute myeloid leukemia patients.

Artificial Intelligence has the potential to reshape the landscape of clinical trials through innovative applications, with a notable advancement being the emergence of synthetic patient generation. This process involves simulating cohorts of virtual patients that can either replace or supplement real individuals within trial settings. By leveraging synthetic patients, it becomes possible to eliminate the need for obtaining patient consent and creating control groups that mimic patients in active treatment arms.

A practical algorithm for acute myeloid leukaemia diagnosis following the updated 2022 classifications.

Disease classification of complex and heterogenous diseases, such as acute myeloid leukaemia (AML), is continuously updated to define diagnoses, appropriate treatments, and assist research and education. Recent availability of molecular profiling techniques further benefits the classification of AML. The World Health Organization (WHO) classification of haematolymphoid tumours and the International Consensus Classification of myeloid neoplasms and acute leukaemia from 2022 are two updated versions of the WHO 2016 classification.

Financial Toxicity and Health-Related Quality of Life Profile of Patients With Hematologic Malignancies Treated in a Universal Health Care System.

Purpose: We investigated the association of financial toxicity (FT) with the health-related quality of life (HRQoL) profile of patients with hematologic malignancies treated in a universal health care system.

Methods: We did a secondary analysis of six multicenter studies enrolling patients with hematologic malignancies. FT was evaluated using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).

Towards personalized prevention of Herpes zoster infection in patients with hematologic diseases or hematopoietic stem cell transplant recipients: a position paper from an ad hoc Italian expert panel.

The identification of patients at high risk of Herpes zoster (HZ) requiring a preventive strategy with antiviral prophylaxis and anti-HZ vaccine is a clinically relevant issue in patients with immunological impairment. The absence of trials comparing vaccination to pharmacological prophylaxis or defining their sequential use makes the optimal preventive strategy uncertain. This article presents the results of group discussion among a panel of experts convened ad hoc to review the literature regarding antiviral prophylaxis and vaccine efficacy and safety in populations with malignant and non-malignant hematologic diseases, and in subjects submitted to hematopoietic stem cell transplantation.

Germline predisposition traits in allogeneic hematopoietic stem-cell transplantation for myelodysplastic syndromes: a survey-based study and position paper on behalf of the Chronic Malignancies Working Party of the EBMT.

The recent application of whole exome or whole genome sequencing unveiled a plethora of germline variants predisposing to myeloid disorders, particularly myelodysplastic neoplasms. The presence of such variants in patients with myelodysplastic syndromes has important clinical repercussions for haematopoietic stem-cell transplantation, from donor selection and conditioning regimen to graft-versus-host disease prophylaxis and genetic counselling for relatives. No international guidelines exist to harmonise management approaches to this particular clinical scenario.

Microenvironment in acute myeloid leukemia: focus on senescence mechanisms, therapeutic interactions, and future directions.

Acute myeloid leukemia (AML) is a disease with a dismal prognosis, mainly affecting the elderly. In recent years, new drugs have improved life expectancy and quality of life, and a better understanding of the genetic-molecular nature of the disease has shed light on previously unknown aspects of leukemogenesis. In parallel, increasing attention has been attracted to the complex interactions between cells and soluble factors in the bone marrow (BM) environment, collectively known as the microenvironment.

Health-related Quality of Life Profile of Newly Diagnosed Patients With Myelodysplastic Syndromes by Age, Sex, and Risk Group: A Real-world Study by the GIMEMA.

Health-related quality of life (HRQoL) is an important goal of therapy for patients with myelodysplastic syndromes (MDS); however, little is known about HRQoL of these patients at clinical presentation. We report HRQoL profile of newly diagnosed patients with MDS across both the the International Prognostic Scoring System (IPSS) and IPSS-Revised (IPSS-R) classifications, stratified by sex and age group categories, aiming to also establish European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) reference values for these patients. Analysis was based on 927 patients with a median age of 73.