Publications by authors named "Lydia Roy"
Chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia patients largely benefit from an expanding tyrosine kinase inhibitors (TKIs) toolbox that has improved the outcome of both diseases. However, TKI success is continuously challenged by mutation-driven acquired resistance and therefore, close monitoring of clonal genetic diversity is necessary to ensure proper clinical management and adequate response to treatment. Here, we report the case of a ponatinib-resistant Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patient harboring a BCR::ABL1 p.
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- * The DAstop2 study examined patients who previously failed a treatment-free remission (TFR) attempt, re-treating them with dasatinib for two years and assessing their ability to stop TKIs again.
- * Results showed that 61%, 56%, and 46% of patients maintained TFR at 6, 12, and 24 months after attempting a second stop, demonstrating that this approach is safe and effective for many patients.
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- Current risk scores for thrombotic events in myeloproliferative neoplasms (MPN) fail to differentiate between arterial and venous thrombosis, even though they have different causes and implications.
- A new score called ARTS, which considers factors like prior arterial thrombosis, age over 60, cardiovascular issues, and specific gene mutations, effectively stratifies patients into low- and high-risk groups for arterial thrombosis.
- Conversely, the VEnous Thrombosis Score (VETS), which only looks at prior venous thrombosis and JAK2 mutations, does not perform well, highlighting the need for better venous risk assessments that address its complexity.
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- Chronic myeloid leukemia (CML) is treated with special pills called tyrosine kinase inhibitors, and one of them is called bosutinib.
- Bosutinib is used to help adult patients with CML, either as a first treatment or if other treatments haven't worked.
- Doctors found that bosutinib can cause side effects like stomach problems and liver issues, so a group of experts made guidelines to help manage these side effects and keep patients safe while they are being treated.
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- Accelerated phase chronic myeloid leukemia (AP-CML) has a poorer prognosis than chronic phase (CP-CML), prompting researchers to test second-generation tyrosine kinase inhibitors (TKI2) as an initial treatment due to their reduced toxicity.
- In a study of 69 newly diagnosed patients with AP-CML, various health parameters were measured, revealing worse conditions in those with hematologic AP compared to cytogenetically defined AP.
- Regardless of the type of TKI2 treatment used, the patients achieved similar rates of clinical response and overall survival, suggesting that TKI2 can effectively manage AP-CML and mitigate the challenges associated with its advanced disease phase.
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- * A total of 79 patients participated, and the primary goal was to assess the cumulative molecular response rates over 12 months, with results showing significant rates of deep molecular response at 5 years.
- * While grade 3 neutropenia was common, it didn't lead to severe infections, and most patients continued the Peg-IFN treatment for a substantial time, resulting in notable molecular response rates after 12 and 24 months.
Musculoskeletal (MSK) pains have been reported during TKI treatment or after its discontinuation in patients with chronic myeloid leukemia (CML). We hypothesized that MSK pains originate from calcific tendinopathy according to preliminary clinical observations. We conducted a retrospective study including CML patients divided into three groups: patients with MSK pain during TKI treatment; asymptomatic patients during TKI treatment; patients with MSK pain after TKI discontinuation.
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- Eosinophilic disorders are rare and have diverse causes; this report focuses on a unique case involving a 67-year-old man with a myeloid neoplasm linked to eosinophilia and a genetic issue with the PDGFRB gene.
- The patient presented with cerebellous ataxia and laboratory tests showed low blood cell counts and high eosinophil levels, suggesting an atypical form of myeloproliferative neoplasm.
- After diagnosis, the patient was treated with imatinib and intravenous immunoglobulin, leading to significant improvements, highlighting the importance of genetic analysis in managing similar cases with hypereosinophilia.
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- Several fusion genes linked to leukemia, like BCR::ABL1 and PML::RARA, have targeted therapies that improve outcomes, but relapse still poses a challenge.
- Current myeloid next-generation sequencing (NGS) methods often miss detecting these fusion genes, complicating analysis of disease progression and treatment strategies.
- A new sequencing approach (aCAP-Seq) and bioinformatics tool (HmnFusion) demonstrate high accuracy in detecting these fusions, allowing better understanding of clonal dynamics in leukemia patients and supporting insights into their resistance to treatments.
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- A retrospective study evaluated the safety of three JAK inhibitors (ruxolitinib, tofacitinib, baricitinib) using data from the WHO database, focusing on their associated adverse events.
- The analysis found a significant link between these drugs and various adverse events, particularly infectious diseases, musculoskeletal issues, and certain cancers, with ruxolitinib showing a notable risk for viral, fungal, and mycobacterial infections.
- Tofacitinib was specifically associated with gastrointestinal perforations, while no significant increase in major cardiovascular events was reported across the drugs studied.
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- HSCT recipients have a high risk of severe COVID-19 and show altered immune responses to vaccinations; this study focused on how well they responded to the BNT162b2 mRNA vaccine.
- A significant number of HSCT recipients were given a third vaccine dose if their antibody levels were low a month after the second dose; six months later, the antibody levels declined but 72% still had protective levels.
- Factors like immunosuppressive treatment and low lymphocyte counts were linked to reduced antibody levels, and a small number of participants experienced COVID-19 infections, with one resulting in death.
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- Dasatinib, a medication for chronic myeloid leukaemia (CML), was studied for its potential to cause pleural effusion (fluid buildup in the lungs) in patients taking it.
- A clinical trial was conducted with patients taking 100 mg of dasatinib, assessing whether therapeutic drug monitoring (TDM) could reduce significant side effects by comparing a dose-reduction strategy with standard care.
- Although the main goal of reducing adverse events wasn't achieved due to early complications, TDM significantly lowered the incidence of pleural effusion in the long run while maintaining similar molecular responses across treatment groups.
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- The study looked at how different gene mutations affect the health of people with myelofibrosis, a type of blood disease.
- Researchers analyzed 479 patients and grouped them based on specific mutations to see how these groups relate to worsening conditions or death.
- They found that mutations in certain genes like TP53 and high-risk genes made it more likely for patients to get worse or die, while a mutation in the ASXL1 gene alone didn’t have a significant negative impact.
Long-term outcome of imatinib 400 mg compared to imatinib 600 mg or imatinib 400 mg daily in combination with cytarabine or pegylated interferon alpha 2a for chronic myeloid leukaemia: results from the French SPIRIT phase III randomised trial.
Francois Guilhot Françoise Rigal-Huguet Joëlle Guilhot Agnès-Paule Guerci-Bresler Frédéric Maloisel Lydia Roy
Leukemia
August 2021
Article Synopsis
- - The SPIRIT trial is a long-term study that compares the effectiveness of various treatments for chronic-phase chronic myeloid leukaemia (CML), involving 787 patients followed for an average of 13.5 years.
- - Overall and progression-free survival rates after 15 years were similar across four treatment groups, ranging from 80% to 87%, suggesting comparable effectiveness of different combinations.
- - The combination of imatinib with pegylated interferon alpha2a resulted in significantly better molecular response rates compared to imatinib alone, although toxicity led to treatment cessation for some patients.
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- - The study examines how mutations in calreticulin (CALRm) impact patients with essential thrombocythemia and myelofibrosis, showing that these mutations primarily affect blood cells and lead to early clonal dominance in hematopoietic stem and progenitor cells (HSPC).
- - Type 1 CALRm spreads more easily in lymphoid cells than type 2 CALRm and is linked to a greater increase in various blood progenitors, while both types increase megakaryocytic progenitors and show different effects on signaling pathways.
- - Results indicate that CALRm mutations serve as both initial and phenotypic events in the disease progression, with type 1 CALRm exhibiting a stronger influence on blood
Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study.
Emilie Cayssials Jose Torregrosa-Diaz Pilar Gallego-Hernanz Florence Tartarin Thomas Systchenko Lydia Roy
Cancer
August 2020
Article Synopsis
- Long-term treatment-free remission (TFR) is a new goal for chronic myeloid leukemia (CML) patients, and dose reductions of tyrosine kinase inhibitors (TKIs) may enhance life quality while minimizing side effects.
- A study analyzed 77 CML patients who stopped TKIs, focusing on 26 who were on low-dose TKIs before discontinuation, with results showing that low-dose patients had better TFR rates compared to those on full doses.
- The findings suggest that low-dose TKIs do not negatively affect TFR, but further randomized clinical trials are needed to confirm these results and better understand the potential of TKI dose reductions prior to stopping treatment.*
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- Kinase inhibitors, like dasatinib, are promising for targeted cancer therapy but also have effects on the immune system, particularly T-cells and NK-cells.
- Research suggests dasatinib may also affect non-conventional T-αβ cell subsets, such as iNKT and a new CD8 T-cell subset, by promoting an activated and anti-tumor phenotype.
- In both mice and humans, dasatinib treatment increased the frequency of these innate T-cell subsets, showing its potential to enhance immune responses and paving the way for combined chemotherapy and immunotherapy approaches.
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- The study focuses on the immune mechanisms behind treatment-free remission (TFR) in chronic myeloid leukemia (CML), highlighting the lack of defined correlations with CD8(+) T-cell types.
- Researchers identified a new subset of CD8(+) T-cells called innate CD8(+) T-cells in CML patients who enjoyed TFR for over two years, showing a significant increase in their functionality compared to control and treated patients.
- The findings suggest a positive relationship between the levels of innate CD8(+) T-cells and natural killer cells, indicating a potential new biomarker profile for successful TFR in CML patients.