Publications by authors named "Valeria Santini"
Lenalidomide in Transfusion-Dependent IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes and Isolated Del(5q): Results of a European Postauthorization Safety Surveillance Study.
Clin Lymphoma Myeloma Leuk
October 2024
Article Synopsis
- This study evaluated the safety and effectiveness of lenalidomide in patients with transfusion-dependent myelodysplastic syndromes (MDS) associated with a specific genetic deletion (del[5q]), focusing on its use in routine clinical care from 2014 to 2022.
- A total of 296 patients were involved, with key findings showing a 24-month cumulative incidence of acute myeloid leukemia (AML) progression at 12.7% and an overall survival probability of 78.3% at 24 months.
- The study reported that over two-thirds of patients experienced serious side effects, with 35.5% discontinuing treatment due to these adverse events, but no new safety issues were identified
Article Synopsis
- The WHO and International Consensus Classification 2022 aim to improve diagnosis and treatment decisions for myelodysplastic syndromes, but disparities in their implementation exist.
- A panel of experts used a data-driven method and the Delphi consensus process to align the two classifications, focusing on genomic features to create harmonized labels for distinct clusters.
- Key findings identified nine genomic clusters, with the most significant linked to biallelic TP53 inactivation, and highlighted the inadequacy of traditional morphological assessments in capturing the complexity of these diseases.
Article Synopsis
- Myelodysplastic neoplasms/syndromes (MDS) are a diverse set of diseases marked by ineffective blood cell production.
- Recent classification systems by the World Health Organization and the International Consensus have provided more detailed categorizations of MDS based on morphology and genetics.
- A comprehensive and systematic approach is essential for the accurate diagnosis and classification of MDS, as outlined by the International Consortium for MDS (icMDS).
Article Synopsis
- Lenalidomide (LEN) can help 60-70% of patients with del(5q) myelodysplastic neoplasm achieve independence from red blood cell transfusions (RBC-TI), but there's a concern about its toxicity and cost.
- The HARMONY Alliance study followed 118 low-intermediate risk MDS patients who discontinued LEN, finding that 50 lost RBC-TI after a median of 49 months.
- Factors like having a low transfusion burden before treatment, completing at least 12 LEN cycles, being younger, and having higher hemoglobin levels at withdrawal were linked to longer RBC-TI duration after discontinuing LEN.
Article Synopsis
- Mutations in the TP53 gene, especially multihit alterations, are linked to worse clinical outcomes in patients with myelodysplastic syndrome (MDS).
- This study analyzed TP53 abnormalities in 682 patients with MDS who had an isolated deletion of chromosome 5 (MDS-del(5q)), revealing that 24% had multihit mutations, indicating a greater risk for leukemic transformation.
- The study found that the effect of monoallelic mutations varies with the variant allele frequency (VAF); lower VAF (<20%) behaved like wild-type TP53, while higher VAF (≥20%) showed outcomes similar to multihit mutations, highlighting the need for careful consideration of TP53 status in
Article Synopsis
Relevance of germline (GL) predisposition in myelodysplastic syndromes (MDSs) was stressed in both 2022 WHO and International Consensus classifications, but its incidence is probably underestimated, especially in young adult patients. We selected a cohort of 31 consecutive de novo MDS patients with unusual young age (<60 years). We performed exome sequencing (ES) on DNA extracted from noninvasive sources (peripheral blood and saliva), filtering for a panel of 344 genes specifically tailored for detecting GL variants related to clonal and nonclonal cytopenia.
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- Myelodysplastic syndromes (MDS) are blood disorders marked by irregularities in myeloid cells and low blood cell counts, often caused by genetic mutations, though classification has mostly focused on cell appearance.
- A study analyzing genomic data from over 3,200 MDS patients identified 16 distinct molecular subtypes, revealing varied clinical outcomes, with the majority of patients (86%) fitting into specific genetic groups linked to different survival rates.
- The findings suggest that understanding these genetically defined subgroups can enhance MDS classification and inform future treatment strategies, emphasizing the importance of genetic insight in managing the disease.
Purpose: Rare cancers constitute over 20% of human neoplasms, often affecting patients with unmet medical needs. The development of effective classification and prognostication systems is crucial to improve the decision-making process and drive innovative treatment strategies. We have created and implemented MOSAIC, an artificial intelligence (AI)-based framework designed for multimodal analysis, classification, and personalized prognostic assessment in rare cancers.
View Article and Find Full Text PDFNotable treatment advances have been made in recent years for patients with myelodysplastic syndromes/neoplasms (MDS), and several new drugs are under development. For example, the emerging availability of oral MDS therapies holds the promise of improving patients' health-related quality of life (HRQoL). Within this rapidly evolving landscape, the inclusion of HRQoL and other patient-reported outcomes (PROs) is critical to inform the benefit/risk assessment of new therapies or to assess whether patients live longer and better, for what will likely remain a largely incurable disease.
View Article and Find Full Text PDFMutations in Acute Leukemias and Myelodysplastic Syndromes: Insights and Treatment Updates.
Am Soc Clin Oncol Educ Book
June 2024
mutations are found in 5%-10% of de novo myelodysplastic syndrome (MDS) and AML cases. By contrast, in therapy related MDS and AML, mutations in are found in up to 30%-40% of patients. The majority of inactivating mutations observed in MDS and AML are missense mutations localized in a few prevalent hotspots.
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- Advancements in understanding myelodysplastic neoplasms (MDS) have revealed important cellular and molecular factors that influence disease progression, highlighting the significance of immune dysregulation in the bone marrow during MDS evolution.
- Despite these advancements, immunotherapy for MDS has lagged due to a lack of effective immune classifications for patient stratification and no widely accepted immune panels for clinical use.
- To address these challenges, the i4MDS consortium proposes standardized immune monitoring approaches, including flow cytometry panels and cytokine assays, aiming to improve patient stratification and develop predictive markers for treatment response in MDS.
Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes.
J Clin Oncol
August 2024
Article Synopsis
- Allogeneic hematopoietic stem-cell transplantation is the only curative option for patients with myelodysplastic syndromes, and the timing of this treatment is crucial for maximizing benefits and minimizing risks.
- A decision support system was developed to identify the optimal timing for HSCT based on clinical and genomic data from a large study of over 7,000 patients, comparing outcomes using the Molecular International Prognostic Scoring System (IPSS-M) against traditional scoring methods.
- The findings suggest that patients with lower risk can benefit from delaying transplantation, while those at higher risk should undergo it immediately, indicating that the IPSS-M strategy significantly improves life expectancy and supports personalized treatment plans.
Article Synopsis
- Mutations in the UBA1 gene, which are linked to VEXAS syndrome, have been found in patients with myelodysplastic syndromes (MDS), with a study identifying 7% of a cohort having specific UBA1 mutations.
- An additional sequencing analysis of a larger group revealed 1% with other potentially harmful variants, and all 40 identified patients with likely/pathogenic mutations were male with various MDS subtypes.
- Most patients with UBA1 mutations exhibited symptoms consistent with VEXAS syndrome, suggesting that routine screening for UBA1 mutations should be considered in MDS management.
Article Synopsis
- - Chronic myelomonocytic leukemia (CMML) is a complex disease that can display both myeloproliferative and myelodysplastic characteristics, making treatment decisions particularly challenging for older patients with other health issues.
- - Allogeneic hematopoietic cell transplantation (allo-HCT) is currently the only potential cure for CMML, but due to the procedure's toxicity and lack of definitive studies, the choice between allo-HCT and less intensive treatments requires careful consideration.
- - The European Society for Blood and Marrow Transplantation has released new best practice recommendations for allo-HCT in CMML, emphasizing that if patients are candidates for transplantation, it should ideally be done upfront, without prior treatments,
Background: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes.
Methods: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries.
Article Synopsis
- The study focuses on patients with lower-risk myelodysplastic syndromes (LR-MDS) who depend on red blood cell transfusions and are either not responding to current treatments or are ineligible for them, particularly erythropoiesis-stimulating agents (ESAs).
- It involves a phase 3 clinical trial comparing the effectiveness of imetelstat (a telomerase inhibitor) to a placebo in achieving red blood cell transfusion independence, involving 178 participants across various countries.
- The primary goal was to measure the percentage of patients who went at least 8 weeks without needing transfusions after starting treatment, with results from this study expected to provide insights into a potential new treatment
GATA2 deficiency is a rare disorder encompassing a broadly variable phenotype and its clinical picture is continuously evolving. Since it was first described in 2011, up to 500 patients have been reported. Here, we describe a cohort of 31 Italian patients (26 families) with molecular diagnosis of GATA2 deficiency.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) treatment is challenging in older patients. There is a lack of evidence-based recommendations for older patients ≥70, a group largely underrepresented in clinical trials. With new treatment options being available in recent years, recommendations are needed for these patients.
View Article and Find Full Text PDFClassification, risk stratification and response assessment in myelodysplastic syndromes/neoplasms (MDS): A state-of-the-art report on behalf of the International Consortium for MDS (icMDS).
Blood Rev
November 2023
Article Synopsis
- - The International Consortium for MDS has updated guidelines on classification, prognostication, and response assessment for myelodysplastic syndromes/neoplasms (MDS), focusing on recent changes in the WHO and ICC classifications.
- - The report compares traditional risk assessment tools with newer molecular approaches, addressing the limitations of existing criteria in measuring treatment effectiveness.
- - Emphasizing patient-centered care, the review highlights the importance of quality-of-life assessments and presents how the latest IWG response criteria improve the evaluation of therapeutic outcomes.