Publications by authors named "Jeffrey E Lancet"
Article Synopsis
- The study compared the outcomes of AML patients treated with a combination of hypomethylating agents and venetoclax, focusing on various levels of remission defined by ELN 2022.
- Among 120 patients, the best responses were complete remission (43.3%), partial remission (18.3%), incomplete remission (25.8%), and morphologic leukemia-free state (12.5%).
- The results indicated that those with MLFS had a history of prior myeloid malignancies and had worse overall survival and relapse-free survival compared to those who achieved better response categories.
Dasatinib is one of the second generation tyrosine kinase inhibitors (TKI) which is approved for the treatment of patients with chronic phase CML (CP-CML) both in the front line and in the second line setting. Pleural effusion (PE) is a unique toxicity associated with dasatinib use. Our aim was to study the incidence of pleural effusion in our cohort of patients who were treated with dasatinib for CP-CML and the safety upon TKI switch.
View Article and Find Full Text PDFBackground: Hypomethylating agent + venetoclax is an effective frontline combination for acute myeloid leukemia, but its efficacy and safety in post-allogeneic hematopoietic cell transplant (alloHCT) relapse remain underexplored. Outcomes have been poor for this population, with no standard treatment.
Patients And Methods: We retrospectively analyzed 72 Ven-naïve patients who received hypomethylating agents + venetoclax at relapse following alloHCT and aimed to evaluate the rates of complete remission with or without hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity, CR/CRi duration, and overall survival.
Article Synopsis
- The study focuses on the progression patterns of low-risk myelodysplastic syndrome (MDS) in a cohort of 1,914 patients, categorizing them into four distinct groups based on their disease progression.
- Key risk factors identified for progression include male gender, low blood cell counts, high bone marrow blasts, and certain genetic mutations, with specific mutations such as SRSF2 correlating with a higher risk of transformation to acute myeloid leukemia (AML).
- Notably, about 13.1% of patients with stable low-risk MDS died within two years of diagnosis, often due to complications related to cytopenia, highlighting the importance of understanding disease progression to improve treatment strategies.
Article Synopsis
- The swimmer plot visually represents the clinical journey of patients with core binding factor acute myeloid leukemia who received allogeneic stem cell transplants.
- It illustrates important milestones, such as treatment phases and survival times, helping to track each patient's progress over time.
- This analysis aids in understanding treatment outcomes and can guide future research and patient management strategies.
Article Synopsis
- A retrospective study evaluated the impact of next-generation sequencing (NGS) mutations on outcomes in patients with secondary acute myeloid leukemia (sAML) who were treated with CPX-351 from 2017 to 2021.
- Common mutations included DNMT3A, SRSF2, RUNX1, TET2, ASXL1, and BCOR, with a median overall survival (mOS) of 47 months for the cohort.
- While patients who cleared their mutations experienced longer mOS and relapse-free survival (RFS) numerically, the differences were not statistically significant, and alloSCT improved RFS regardless of mutational status.
Article Synopsis
- The Molecular International Prognostic Scoring System (IPSS-M) is a new model for assessing risk in patients with myelodysplastic syndromes (MDS) that incorporates genetic mutation data for better accuracy compared to previous systems like IPSS and IPSS-R.
- A large study involving 2,355 MDS patients confirmed the IPSS-M's effectiveness in predicting overall survival (OS), leukemia-free survival (LFS), and the risk of leukemic transformation.
- The model categorizes patients into six risk groups, showing significant differences in median survival times, which supports the potential of IPSS-M to enhance treatment decisions for MDS patients.
Purpose: Belinostat is an intravenous histone deacetylase inhibitor with approval for T-cell lymphomas. Adavosertib is a first in class oral Wee1 inhibitor. Preclinical studies of the combination demonstrated synergy in various human acute myeloid leukemia (AML) lines as well as AML xenograft mouse models.
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- EZH2 mutations in myelodysplastic syndrome (MDS) are linked to poorer overall survival, with 4.7% of patients in a study showing these mutations.* -
- Patients with EZH2 mutations tend to be older and have lower response rates to treatments compared to those without the mutation; their median overall survival was notably worse at 30.8 months.* -
- Co-existing mutations like ASXL1 and RUNX1, along with chromosome 7 abnormalities, are associated with even poorer outcomes, highlighting the need for targeted therapies in future clinical trials.*
CPX-351 (Europe: Vyxeos liposomal; United States: Vyxeos) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. In a phase 3 study in older adults with newly diagnosed, high-risk/secondary AML, CPX-351 improved the remission frequency, overall survival, and post-transplant survival versus 7 + 3. This post hoc analysis evaluated the final 5-year follow-up outcomes according to the European LeukemiaNet 2017 risk classification.
View Article and Find Full Text PDFBackground: Genomic landscape of extramedullary acute myeloid leukemia (EM-AML), including myeloid sarcoma (MS) and leukemia cutis (LC), is not well characterized. The potential utility of next-generation sequencing (NGS) using EM tissue is not established.
Methods: In this multicenter retrospective study, clinical and NGS data were collected on patients with EM-AML.
Background: Thrombocytopenia in patients with myelofibrosis (MF) is prognostically detrimental and poses a therapeutic challenge. MF patients with thrombocytopenia are considered high-risk by most prognostic models and their distinct phenotype has given rise to the emerging concept of cytopenic MF. Yet, the mechanisms underlying thrombocytopenia in MF are poorly understood.
View Article and Find Full Text PDFSplicing factor 3B subunit 1 (SF3B1) somatic mutation in the context of therapy-related myelodysplastic syndromes (t-MDS) has not been well defined. In a large cohort of patients with MDS, those with known SF3B1 somatic mutation were compared as de novo MDS (n = 289) and t-MDS with mutant SF3B1 (SF3B1 ; n = 31). Baseline characteristics, concomitant mutations, and acute myeloid leukaemia (AML) transformation were similar between the two groups.
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- Patients with cancer face higher risks of severe illness and death from COVID-19, and the effectiveness of the mRNA-1273 vaccine in these patients needed further investigation.
- The study aimed to measure antibody responses to the mRNA-1273 vaccine in cancer patients, examining factors that might affect their immune response to the vaccine.
- Among 515 participants, 90.3% showed seropositivity after the second vaccine dose, with lower rates in those with hematologic and lymphoid cancers compared to those with solid tumors.
Recent studies demonstrated that MYC epigenetically regulates AML cell survival and differentiation by suppressing IDH1/2-TET2-5hmC signaling and that MYC overexpression is associated with poor survival outcomes in multiple AML patient cohorts. However, the oncogenic roles of MYC in MDS remain to be explored. A total of 41 patients with de novo MDS were retrospectively identified using the Total Cancer Care database at the Moffitt Cancer Center.
View Article and Find Full Text PDFBackground: CPX-351 (United States: Vyxeos; Europe: Vyxeos Liposomal), a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio, is approved by the US FDA and the EMA for the treatment of adults with newly diagnosed therapy-related acute myeloid leukemia or acute myeloid leukemia with myelodysplasia-related changes. In a pivotal phase 3 study that evaluated 309 patients aged 60 to 75 years with newly diagnosed high-risk/secondary acute myeloid leukemia, CPX-351 significantly improved median overall survival versus conventional 7 + 3 chemotherapy (cytarabine continuous infusion for 7 days plus daunorubicin for 3 days), with a comparable safety profile. A Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of the phase 3 study was performed to compare survival quality between patients receiving CPX-351 versus conventional 7 + 3 after 5 years of follow-up.
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- The study investigates the effects of ruxolitinib, a JAK1/2 inhibitor, on patients with chronic myelomonocytic leukemia (CMML), a rare type of leukemia with no effective treatments, focusing on its potential to downregulate GM-CSF signaling.
- In a phase I/II clinical trial, 50 CMML patients were treated, along with 49 patient-derived xenografts (PDX) to assess the drug’s efficacy and safety, resulting in a clinical overall response rate of 38%.
- Results suggested that ruxolitinib is clinically effective with manageable side effects, and the study highlights the usefulness of PDX models in predicting patient responses, thereby validating its approach in investigating