Publications by authors named "Natalia Curto-Garcia"
Polycythemia Vera: Barriers to and Strategies for Optimal Management.
Blood Lymphat Cancer
December 2023
Polycythemia vera (PV) is a subtype of myeloproliferative neoplasms characterized by impaired quality of life and severe complications. Despite the increasingly in-depth knowledge of this condition, it necessitates a multifaceted management approach to mitigate symptoms and prevent thrombotic and hemorrhagic events, ensuring prolonged survival. The therapeutic landscape has been revolutionized in recent years, where venesection and hydroxycarbamide associated with antiplatelet therapy have a central role and are now accompanied by other drugs, such as interferon and Janus kinase inhibitors.
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- Polycythemia vera (PV) is a blood disorder linked to JAK/STAT activation, and ruxolitinib has been shown to effectively manage high-risk patients by controlling blood counts and alleviating symptoms.
- The MAJIC-PV trial compared ruxolitinib to best available therapy (BAT) in patients who were resistant or intolerant to hydroxycarbamide, with the main goal of achieving a complete response (CR) within a year.
- Results showed that ruxolitinib led to a significantly higher CR rate (43% vs. 26% for BAT), better duration of response and symptom improvement, and a stronger correlation between molecular response and patient outcomes like event-free survival (
Article Synopsis
- Standard therapy for myelofibrosis typically involves Janus kinase inhibitors (JAKis), but they have low response rates and high dropout rates, indicating a need for better treatments like pelabresib (CPI-0610), a bromodomain and extraterminal domain inhibitor.
- In the MANIFEST phase II study, patients who had not previously received JAKis were treated with pelabresib and ruxolitinib, showing promising results: 68% of patients achieved a significant spleen volume reduction after 24 weeks, and many also experienced symptom relief and improved hemoglobin levels.
- The combination therapy was generally well tolerated, with 95% of participants continuing treatment beyond 24 weeks,
Article Synopsis
- Pegylated interferons, particularly peginterferon alfa-2a, are commonly used to treat Myeloproliferative Neoplasms (MPN), but a newer drug called ropeginterferon alfa-2b (ropegIFN) has emerged as an option, especially for Polycythaemia Vera (PV).
- RopegIFN received a recommendation from the European Medicine Authority (EMA) and FDA approval in November 2021 after positive results from Phase III trials.
- The study highlights the safety and tolerability of ropegIFN in MPN patients, confirming its efficacy in treating PV and its potential use during pregnancy.
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- Myeloproliferative neoplasms (MPNs) are rare in individuals under 25, and a study examined 444 such patients over a median follow-up of 9.7 years across 38 centers globally.
- The study found that 11.1% had a history of thrombosis, with higher risks associated with the JAK2V617F mutation and hyperviscosity symptoms, while new thrombotic and hemorrhagic events occurred at significant rates.
- It highlighted that disease transformation, particularly to myelofibrosis, was common, with splenomegaly identified as a new risk factor, indicating a need for updated management guidelines for young MPN patients.
Article Synopsis
- - The study investigates potential new treatment options for chronic myeloid leukaemia (CML) to enhance effectiveness for patients who don't respond to current therapies and to assess if some patients can stop taking tyrosine kinase inhibitors (TKIs).
- - Findings show that at diagnosis, there is a higher presence of regulatory T cells (Tregs) and markers of T-cell exhaustion, particularly in patients with advanced disease.
- - Increased levels of inflammatory cytokines, such as TNF-a and IL-6, were found in the plasma of newly diagnosed patients, indicating a heightened inflammatory response likely due to the accumulation of cancer-related antigens.
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- Patients with chronic myeloid leukaemia (CML) receiving targeted cancer treatments, like tyrosine kinase inhibitors (TKIs), are considered highly vulnerable to SARS-CoV-2 and may not respond adequately to a single dose of the Pfizer-BioNTech COVID-19 vaccine.
- A study evaluated immune responses in 16 CML patients after their first BNT162b2 vaccine dose, finding that 87.5% developed anti-Spike immunoglobulin G and all patients generated a neutralizing antibody response.
- Additionally, 93.3% of evaluable patients showed T-cell responses, with 80% displaying polyfunctional responses, indicating that a single vaccine dose is immunogenic for most CML patients
Single dose of BNT162b2 mRNA vaccine against SARS-CoV-2 induces high frequency of neutralising antibody and polyfunctional T-cell responses in patients with myeloproliferative neoplasms.
Patrick Harrington Hugues de Lavallade Katie J Doores Amy O'Reilly Jeffrey Seow Natalia Curto-Garcia
Leukemia
December 2021
Article Synopsis
- Myeloproliferative neoplasm-unclassifiable (MPN-U) is a type of blood cancer that shows specific features resembling other blood disorders but does not fully fit those diagnoses.
- A study involving 1512 patients found that 82 had MPN-U, with common symptoms including high lactate dehydrogenase levels, elevated platelet counts, and abnormal megakaryocytes in biopsies.
- Thrombosis occurred in 21% of cases, and patients with lower platelet counts or high white blood cell counts at the start had reduced event-free survival, showing a need for developing prognostic scoring systems for MPN-U.
Evidence of robust memory T-cell responses in patients with chronic myeloproliferative neoplasms following infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
Patrick Harrington Claire N Harrison Richard Dillon Deepti H Radia Katayoun Rezvani Natalia Curto-Garcia
Br J Haematol
May 2021
In a multicenter European retrospective study including 162 patients with COVID-19 occurring in essential thrombocythemia (ET, n = 48), polycythemia vera (PV, n = 42), myelofibrosis (MF, n = 56), and prefibrotic myelofibrosis (pre-PMF, n = 16), 15 major thromboses (3 arterial and 12 venous) were registered in 14 patients, of whom all, but one, were receiving LMW-heparin prophylaxis. After adjustment for the competing risk of death, the cumulative incidence of arterial and venous thromboembolic events (VTE) reached 8.5% after 60 days follow-up.
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- A study of 175 patients with myeloproliferative neoplasms (MPN) during COVID-19 showed a high mortality rate of 48% in those with myelofibrosis (MF), which is significantly higher than the general population.
- Key factors linked to higher mortality included older age, male gender, lower lymphocyte counts, need for respiratory support, and existing comorbidities, but no significant links were found with essential thrombocythemia or polycythemia vera.
- While Ruxolitinib treatment was more frequent among those who died, stopping the treatment before COVID-19 was associated with increased mortality, indicating the need for further research on how treatment interruptions affect survival in M
Article Synopsis
- The bone marrow niche is a complex environment made up of various cell types that support the growth and maintenance of hematopoietic stem cells, which are crucial for blood formation.
- Recent research has begun to uncover how this niche plays a role in myeloproliferative neoplasms, particularly in disease progression and treatment resistance, influenced by factors like chronic inflammation and immune responses.
- The article aims to review the knowledge of how the bone marrow niche is disrupted in these conditions and to propose potential therapeutic targets that could improve treatment strategies in the future.
Article Synopsis
- Myeloproliferative Neoplasms (MPN) can cause thrombosis, particularly in uncommon areas like splanchnic veins, complicating their management due to increased vascular risks.
- A study including 518 MPN-SVT cases and a control group found that MPN-SVT patients tend to be younger, primarily female, with a high prevalence of the JAK2V617F mutation and a notable rate of hypercoagulable disorders.
- Vitamin K-antagonists were effective in reducing thrombosis recurrence without significant bleeding risks, while esophageal varices were identified as a key risk factor for major bleeding, making them a focus for future treatments.