Publications by authors named "Jean Jacques Kiladjian"
Interferon alpha (IFN-α) is a fascinating molecule with many biological properties yet to be fully understood. Among these properties, several have demonstrated usefulness for targeting malignant cells, including hematopoietic cells from patients with myeloproliferative neoplasms. Indeed, IFN-α has been used for decades across all myeloproliferative neoplasms, but only recently a new form, ropegIFN-α2b, was approved to treat patients with polycythemia vera.
View Article and Find Full Text PDFThe aim of our study was to analyze the potential survival benefit associated with HSCT according to clinico-biological scores which incorporate molecular data (MIPSS70 and MIPSS70+V2) to facilitate decision-making in this context. One transplant (n=241) and one non-transplant cohorts (n=239) were used to test the hypothesis that PMF patients with higher risk molecular score benefit from HSCT. A weighted propensity score was applied to balance confounding factors with the transplanted cohort as reference.
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- BCR::ABL1-negative myeloproliferative neoplasms (MPN) are blood cancers caused by mutations in the JAK-STAT pathway, requiring careful risk evaluation for effective management based on different subtypes like polycythemia vera (PV) and essential thrombocythemia (ET).
- Patients with myelofibrosis (MF) have the worst prognosis, and while hematopoietic stem cell transplantation (HSCT) is the only cure, it carries significant health risks, making survival scoring systems vital for patient management and treatment decision-making.
- The increasing number of clinical risk scores, along with disease complexity, complicates clinicians' efforts to select the best scoring system for predicting patient outcomes in
Despite the advances in the understanding and treatment of myeloproliferative neoplasm (MPN), the disease remains incurable with the risk of evolution to acute myeloid leukemia or myelofibrosis (MF). Unfortunately, the evolution of the disease to MF remains poorly understood, impeding preventive and therapeutic options. Recent studies in solid tumor microenvironment and organ fibrosis have shed instrumental insights on their respective pathogenesis and drug resistance, yet such precise data are lacking in MPN.
View Article and Find Full Text PDFMyeloproliferative neoplasms (MPNs) are characterized by an increased production of blood cells due to the acquisition of mutations such as JAK2. TGF-β, whose secretion is increased in MPN patients, is known to negatively regulate haematopoietic stem cell (HSC) proliferation. Using an isogenic JAK2 or JAK2 wild-type UT-7 cell line we observed that JAK2 cells resist to TGF-β antiproliferative activity.
View Article and Find Full Text PDFSpleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 10/L. Whether this association occurs in patients with thrombocytopenia is unclear.
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- High-molecular risk (HMR) mutations, such as ASXL1 and IDH, are linked to poorer outcomes in myelofibrosis (MF) patients, particularly when combined with lower levels of the JAK2V617F variant allele frequency (VAF).
- Analysis of 124 MF patients showed that HMR mutations significantly impacted prognosis for those with lower JAK2V617F VAF, while this effect was not observed in patients with higher VAF levels.
- The study's findings indicate that having both HMR mutations and a lower JAK2V617F VAF (≤50%) serves as a strong independent risk factor for survival, improving existing prognostic models and prompting the need for further
Article Synopsis
- Most patients with myelofibrosis who are treated with ruxolitinib eventually develop intolerance or relapse, leading to poor survival rates after stopping the drug; hence, the study evaluates fedratinib against best available therapy (BAT).
- The FREEDOM2 trial was a phase 3, open-label study involving 201 patients with myelofibrosis who were either intolerant or had relapsed during ruxolitinib treatment, comparing fedratinib to BAT, with the main goal being the rate of spleen volume reduction after 6 cycles.
- At the data cutoff, 36% of patients treated with fedratinib achieved a significant spleen volume reduction by the end of cycle
Article Synopsis
- - A new framework for defining anemia severity and treatment response in myelofibrosis (MF) aims to improve clinical studies and comparisons as new drugs emerge in this area.
- - The revised criteria will address gender differences in hemoglobin levels and update the definition of transfusion-dependent anemia (TDA) to align with current practices.
- - The updated guidelines introduce specific eligibility thresholds for hemoglobin levels and establish distinct response criteria (major vs. minor) while maintaining a 12-week observation period on treatment.
Article Synopsis
- Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) primarily affect older adults, with fewer cases seen in children and young adults, leading to less knowledge about their symptoms and treatment in these younger demographics.
- Diagnosis in younger patients can be challenging due to the rarity of specific genetic mutations and differences in blood counts compared to adults.
- Effective management of young MPN patients is complex due to their unique needs and longer life expectancies, highlighting the necessity for collaboration between pediatricians and adult hematologists to develop better treatment protocols.
Article Synopsis
- * Recent findings show that adolescents and young adults (15-39 years) can make up to 20% of MPN cases, presenting unique mutations and increased risks of severe complications compared to older patients.
- * There is a pressing need for effective and tolerable treatment options for young patients with MPN, as many will live with the condition for a long time; this review discusses their specific
Article Synopsis
- The phase 3b FREEDOM trial tested the drug fedratinib's effectiveness and safety in patients with intermediate or high-risk myelofibrosis who had low platelet counts and were previously treated with ruxolitinib.
- Despite being cut short due to COVID-19, 38 patients were enrolled, and in the final efficacy analysis, 25.7% achieved the primary goal of spleen volume reduction, while 62.9% had the best overall response leading to symptom improvement.
- The study found that fedratinib led to significant clinical responses with fewer gastrointestinal side effects compared to previous trials, and there were no cases of encephalopathy among participants.
Article Synopsis
- The ACE-536-MF-001 trial studied the effects of luspatercept on myelofibrosis patients, enrolling 95 participants divided into four groups based on their dependency on transfusions and anemia status.
- The primary outcome measured was the anemia response rate, where 14%-26% of patients met the criteria based on their cohort, with significant hemoglobin increases noted, particularly in non-transfusion dependent patients.
- Adverse events were common, with 94% of patients experiencing at least one; the most frequent were hypertension and other manageable issues, while the treatment showed consistent efficacy and safety results similar to previous studies.
Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response.
Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection.
Design, Setting, And Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France.
Article Synopsis
- The ANRS|MIE CoviCompareP study investigated COVID-19 breakthrough infections among vaccinated adults during the Omicron variant's circulation, focusing on those vaccinated with the Pfizer-BioNTech vaccine.
- The study involved healthy adults divided into groups based on previous SARS-CoV-2 infection status and monitored their neutralizing antibodies after vaccination and boosters.
- Results showed that 31% of participants experienced breakthrough infections, with lower infection risks linked to older age, more booster doses, and higher neutralizing antibody levels, especially in those with prior infections.
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- Interferon-based therapies like ropeginterferon alfa-2b are showing promise as potential treatments for essential thrombocythemia (ET), which current therapies don't modify or improve disease progression.
- Ropeginterferon alfa-2b has been effective in treating polycythemia vera (PV) and could similarly benefit ET patients who can't tolerate or are resistant to existing treatments.
- The ongoing ROP-ET trial aims to evaluate its effectiveness over three years, focusing on patient responses, quality of life, and safety, providing crucial data for treatment options in this underserved group.
Article Synopsis
- Bone marrow fibrosis (BMF) is linked to myelofibrosis and can affect prognosis, but this study explores its relationship with treatment outcomes in patients receiving JAK inhibitors momelotinib and ruxolitinib.
- In a study of patients with BMF, only momelotinib showed increased transfusion independence and hemoglobin levels, while ruxolitinib showed a decrease in hemoglobin.
- The findings suggest that changes in BMF do not correlate with clinical improvements or survival benefits, indicating that BMF may not be an effective surrogate marker for assessing the efficacy of JAK inhibitors.
Article Synopsis
- Current treatments for myelofibrosis (MF) mainly involve JAK inhibitors, which help with symptoms but don't significantly improve survival or modify the disease itself.
- Allogeneic-hematopoietic stem cell transplantation is the only potential cure, but it's only available to high-risk patients who are fit enough for the procedure.
- There's a critical need for safer, effective therapies for lower-risk patients, better first-line treatment strategies for intermediate/high-risk patients, and a clear definition of disease modification to reshape clinical trials and improve patient outcomes.
Article Synopsis
- The multidisciplinary clinical investigation center (CIC-P) aims to improve patient access to new drugs, enhance the reputation of French clinical research, and improve the quality of early-phase trials while focusing on rare diseases.
- Since 2017, CIC-P has adopted a quality approach, launching patient care satisfaction surveys to gather feedback, although a planned second survey was delayed by the COVID-19 pandemic.
- The center is pursuing ISO 9001:2015 certification to enhance performance and customer satisfaction by integrating quality improvement tools like PDCA, SWOT analysis, and FMEA, while continuously seeking to understand and meet the expectations of its stakeholders.
Article Synopsis
- - Patients with myelofibrosis suffer from various symptoms due to bone marrow fibrosis and inflammation, and improving these symptoms can enhance their quality of life.
- - This study analyzed data from two phase III trials of momelotinib (SIMPLIFY-1 and SIMPLIFY-2) to determine a meaningful change threshold (MCT) for symptoms, finding it to be 8 points for treatment-naive patients and 6 points for those previously treated.
- - Results showed that momelotinib effectively improved patient symptoms, suggesting that the traditional 50% reduction standard used in clinical trials may be too conservative and that momelotinib offers significant benefits compared to other treatments in myelofibrosis patients.
Article Synopsis
- The study compares the clinical characteristics of primary myelofibrosis (PMF) and secondary myelofibrosis (SMF), highlighting key differences in patient presentation and symptoms.
- It explores the molecular landscape of both conditions, analyzing genetic mutations and other molecular factors that may influence the disease.
- The research also focuses on prognosis scoring systems, assessing how well they predict outcomes and survival rates for patients with PMF and SMF.