Publications by authors named "Eric Delabesse"
According to current recommendations, older AML patients in first complete remission (CR) after induction chemotherapy should receive consolidation with intermediate-dose cytarabine (IDAC). However, no study has demonstrated the superiority of IDAC over other regimen. In this retrospective study, we compared the efficacy of mini-consolidations (idarubicin 8 mg/m day 1, cytarabine 50 mg/m/12 h, day 1-5) and IDAC.
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- Despite initial treatment with midostaurin (MIDO) and chemotherapy in FLT3-mutated acute myeloid leukemia (AML), many patients face relapses, with complete remission rates around 60-70% and over 40% relapsing.
- A study of 150 patients with refractory/relapsed (R/R) AML revealed that those treated with MIDO showed lower persistence of FLT3-ITD mutations compared to those who did not receive MIDO (68% vs. 87.5%).
- The study found that detecting multiple FLT3-ITD clones at diagnosis related to a higher persistence rate of these mutations at relapse, indicating the need for sensitive techniques in FLT3-
Patients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss of heterozygosity (LOH) via uniparental isodisomy. We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secreted 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH.
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- Adult T-cell acute lymphoblastic leukemia (T-ALL) has a low survival rate after it relapses, particularly the early T-cell precursor subtype, which shares similarities with acute myeloid leukemia.
- A case study is presented where a patient relapsed just 3 months post allogeneic stem cell transplantation but achieved complete remission through treatment with azacitidine and has remained on therapy for 9 years.
- The discussion highlights the biological factors contributing to this long-term response and explores the potential benefits of combining hypomethylating agents like azacitidine with other drugs, such as venetoclax, for improved outcomes.
Patients with Core-Binding Factor (CBF) and NPM1-mutated acute myeloid leukemia (AML) can be monitored by quantitative PCR after having achieved first complete remission (CR) to detect morphologic relapse and drive preemptive therapy. How to best manage these patients is unknown. We retrospectively analyzed 303 patients with CBF and NPM1-mutated AML, aged 18-60 years, without allogeneic hematopoietic cell transplantation (HCT) in first CR, with molecular monitoring after first-line intensive therapy.
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- Acute myeloid leukemia (AML) with BCR::ABL1 is classified as an adverse-risk group in the 2022 ELN classification, but its outcomes with modern treatment options like tyrosine kinase inhibitors are not well understood.
- In a study of 20 patients with de novo BCR::ABL1 AML from a large registry, most received standard chemotherapy with imatinib, leading to a high complete remission rate of 94.4%.
- The survival rates suggest BCR::ABL1 AML patients have better outcomes than those classified in traditional adverse-risk categories, indicating they may need reclassification in future treatment guidelines.
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- In patients with acute myeloid leukemia (AML), a higher presence of Vγ9Vδ2 T cells at diagnosis is associated with better overall and relapse-free survival rates.
- This study analyzed immunophenotypic data from 198 newly diagnosed AML patients to determine how Vγ9Vδ2 T-cell frequency impacts prognosis while adjusting for various confounding factors.
- The findings support the importance of Vγ9Vδ2 T cells in AML prognosis and suggest potential treatment strategies that could boost these T-cell responses in patients.
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- Acute myeloid leukemia (AML) with myelodysplasia-related characteristics presents a mixed prognosis, and there's limited understanding of patient outcomes after first-line treatment in refractory or relapsed cases.
- A study involving 183 patients found that the median overall survival was 4.2 months, with no significant survival difference between refractory and relapsed patients; however, patients receiving best supportive care had markedly poorer outcomes.
- The research suggests that both intensive chemotherapy and azacitidine are viable treatment options for this tough-to-treat population, and emphasizes the need for further exploration of new targeted therapies.
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- Researchers created AI-based prediction models using data from 3,687 acute myeloid leukemia patients, focusing on two treatment types: intensive chemotherapy and azacitidine.
- A multilayer perceptron neural network demonstrated prediction accuracies of 68.5% for intensive chemotherapy patients and 62.1% for those treated with azacitidine.
- The Boruta algorithm effectively identified key diagnostic features needed for predictions, streamlining the complexity of data analysis for hematologists and potentially improving treatment decisions.
B cell acute lymphoblastic leukemia (B-ALL) is a multistep disease characterized by the hierarchical acquisition of genetic alterations. However, the question of how a primary oncogene reprograms stem cell-like properties in committed B cells and leads to a preneoplastic population remains unclear. Here, we used the PAX5::ELN oncogenic model to demonstrate a causal link between the differentiation blockade, the self-renewal, and the emergence of preleukemic stem cells (pre-LSCs).
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- Recent research indicates that vitamins C and D may play a role in supporting patients with acute myeloid leukemia (AML) during intensive chemotherapy.!
- A study tracking 431 AML patients from 2015 to 2020 found that those who received vitamin supplementation showed higher vitamin levels and fewer complications like infections compared to those who didn’t.!
- The analysis revealed that vitamin C/D supplementation significantly improved overall survival for patients with the NPM1 mutation, suggesting it could be a beneficial addition to AML treatment protocols.!
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- - The study evaluated the effectiveness and costs of next-generation sequencing (NGS) in treating various hematological cancers in both pediatric and adult patients, collecting data from 26 laboratories with differing practices.
- - Results showed that NGS influenced treatment management for 73.4% of cases, particularly providing prognostic information and aiding treatment adaptations, though about 18.9% of prescriptions had no immediate impact on therapy.
- - The average cost for NGS samples was 191 €, with variations based on the type of panel used, highlighting the need for clear discussions about precision medicine's effects on patient care and financial implications.
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- * In a study of 1091 adult patients, 12.9% had KMT2A-r, with a 5-year relapse rate of 40.7% and overall survival rate of 53.3%. The presence of specific gene alterations like TP53 and IKZF1 correlated with significantly worse outcomes.
- * The analysis showed that measuring minimal residual disease (MRD) using KMT2A markers was more reliable than other methods, indicating that patients responding well early
Tandem duplications (TDs) of the UBTF gene have been recently described as a recurrent alteration in pediatric acute myeloid leukemia (AML). Here, by screening 1946 newly diagnosed adult AML, we found that UBTF-TDs occur in about 3% of patients aged 18-60 years, in a mutually exclusive pattern with other known AML subtype-defining alterations. The characteristics of 59 adults with UBTF-TD AML included young age (median 37 years), low bone marrow (BM) blast infiltration (median 25%), and high rates of WT1 mutations (61%), FLT3-ITDs (51%) and trisomy 8 (29%).
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- Germline mutations in the GATA2 gene increase the risk of developing myeloid cancers, particularly as patients acquire additional genetic mutations over time.
- An analysis of 78 patients revealed an exhaustion of myeloid progenitor cells and frequent somatic mutations in specific genes (STAG2, ASXL1, SETBP1) along with notable chromosomal abnormalities.
- Patients were categorized into three groups based on their bone marrow cell composition, with each group's mutations corresponding to their disease stage, indicating that understanding these mutations can improve patient management and illuminate cancer progression associated with GATA2 mutations.
Unlabelled: Low hypodiploidy defines a rare subtype of B-cell acute lymphoblastic leukemia (B-ALL) with a dismal outcome. To investigate the genomic basis of low-hypodiploid ALL (LH-ALL) in adults, we analyzed copy-number aberrations, loss of heterozygosity, mutations, and cytogenetics data in a prospective cohort of Philadelphia (Ph)-negative B-ALL patients (n = 591, ages 18-84 years), allowing us to identify 80 LH-ALL cases (14%). Genomic analysis was critical for evidencing low hypodiploidy in many cases missed by cytogenetics.
View Article and Find Full Text PDFNPM 1-mutated acute myeloid leukemia (AML) shows unique features. However, the characteristics of "therapy-related" NPM1-mutated AML (t-NPM1 AML) are poorly understood. We compared the genetics, transcriptional profile, and clinical outcomes of t-NPM1 AML, de novo NPM1-mutated AML (dn-NPM1 AML), and therapy-related AML (t-AML) with wild-type NPM1 (t-AML).
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- Acute myeloid leukemia (AML) is linked to leukemic stem cells (LSC), which affect patient responses to chemotherapy and overall survival, highlighting the importance of measuring LSC levels.
- A study evaluated 155 AML patients post-chemotherapy to assess the effectiveness of detecting measurable residual disease (MRD) in both bulk and LSC populations, using unsupervised clustering methods.
- Results showed a significant difference in overall survival rates between patients with positive MRD and those who tested negative, with some patients having negative Bulk MRD but positive LSC MRD, indicating these individuals have an intermediate prognosis.
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- Researchers have developed a new classification system for acute myeloid leukemia (AML) using flow cytometry to identify six stages of differentiation arrest in leukemic cells based on specific protein expressions.
- The study analyzed two patient cohorts and found that different types of AML (stem cell-like versus progenitor-like) display distinct genetic characteristics, proliferation rates, and treatment responses, which influence patient outcomes.
- Factors such as NPM1 mutations are associated with more mature leukemia stages, while other genetic mutations (like CEBPA and RUNX1) help predict the severity and treatment efficacy for AML patients.
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- A new scoring system was developed using data from three European registries involving 1,199 older AML patients (aged 70+) to help select treatment options based on factors like age and performance status.* -
- The scoring system identified three risk groups with varying 5-year overall survival probabilities: lower risk (≥12%), intermediate risk (3-12%), and higher risk (<3%).* -
- This European Scoring System for patients aged 70 and older is practical for everyday use and effectively predicts long-term survival, complete remission, and relapse-free survival in those undergoing intensive chemotherapy.*
Article Synopsis
- The study involved 526 acute myeloid leukemia patients who were not responding to or were relapsing after chemotherapy, with treatment options including intensive salvage chemotherapy, azacitidine, and best supportive care.
- Complete response rates varied significantly among the treatment groups, with intensive chemotherapy showing the best outcomes, while azacitidine had limited effectiveness.
- Predictive factors for worse survival included certain leukemia history, high bone marrow blasts, and adverse genetics, with AZA being beneficial in the short term but lacking in long-term survival for older patients.
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- DDX41 germline mutations are a common cause of a type of cancer called myelodysplastic syndrome and acute myeloid leukemia (AML).
- In a study of 191 patients with these mutations, it was found that most were older men with specific characteristics like low white blood cell counts and fewer genetic changes.
- Patients with these mutations had higher chances of getting better with treatment (94% complete remission) and lived longer compared to those without the mutation, but their chances of relapse became similar after a few years.
High tumor burden before blinatumomab has a negative impact on the outcome of adult patients with B-cell precursor acute lymphoblastic leukemia. A real-world study by the GRAALL.
Haematologica
September 2022
Article Synopsis
- Blinatumomab is a bispecific T-cell engager used for treating B-cell precursor acute lymphoblastic leukemia (B-ALL) in patients who have minimal residual disease (MRD) or are in relapse, with a study analyzing 73 patients receiving this treatment.
- The results showed that high pre-treatment MRD levels correlated with poorer outcomes, specifically shorter relapse-free survival and overall survival rates.
- The study suggests that understanding tumor burden prior to treatment could lead to more personalized strategies for managing relapsed patients, highlighting the importance of MRD levels in treatment planning.