Publications by authors named "Anthony Hunter"
Article Synopsis
- - The drug development for chronic myelomonocytic leukemia (CMML) has lagged behind successes in other related blood diseases, prompting concern among experts.
- - In September 2023, the FDA organized a symposium to address CMML, bringing together regulators and researchers to identify challenges and discuss future strategies for drug development.
- - The discussions focused on issues like clinical trial design, study endpoints, and regulatory considerations to improve therapeutic options for CMML.
SOHO State of the Art Updates and Next Questions | Choosing and Properly Using a JAK Inhibitor in Myelofibrosis.
Clin Lymphoma Myeloma Leuk
September 2024
Article Synopsis
- * Four JAK inhibitors have been approved to manage MF symptoms, with allogeneic stem cell transplantation as a potential cure for higher-risk patients, although it's risky.
- * Newer JAK inhibitors, like pacritinib and momelotinib, are designed to be more effective for patients with low platelet or red blood cell counts, and ongoing research aims to improve treatment outcomes through sequencing therapies and developing novel combinations.
Article Synopsis
- The discovery of the hyperactivation of the JAK-STAT pathway was a key moment in understanding myeloproliferative neoplasms (MPNs) and led to the creation of JAK inhibitors, essential for treating myelofibrosis and polycythemia vera.
- The review covers the efficacy, safety, and pharmacology of four approved JAK inhibitors for MPNs, with a special emphasis on myelofibrosis and discusses their limitations and future treatment strategies.
- While JAK inhibitors have significantly improved patient outcomes, they are not curative and often fail over time; combining them with new targeted therapies might enhance treatment effectiveness.
Article Synopsis
- * The paper explores automating the generation of evidence tables by using language processing techniques, specifically named entity recognition and relation extraction, to analyze RCT abstracts for study outcomes.
- * Two deep neural net models demonstrated the ability to create evidence tables effectively with minimal training data, suggesting a viable pathway towards semi-automated systematic reviews in the future.
Article Synopsis
- Myelodysplastic syndromes (MDS) patients treated with DNMTIs responded according to 2006 IWG criteria, revealing a correlation between complete response (CR) and overall survival (OS).
- A notable number of patients achieved a new classification called CR with partial hematologic recovery (CRh), which showed similar survival rates to CR, suggesting that CRh may be a relevant response category.
- The study analyzed 311 MDS patients and found significant differences in OS based on the response type, advocating for the inclusion of CRh in future response criteria and clinical trials.
Article Synopsis
- * The study reveals three main differentiation trajectories for CMML cells: monocytic, megakaryocyte-erythroid progenitor (MEP), and normal-like, with the monocytic trajectory linked to negative outcomes and increased inflammation.
- * Hypomethylating agents can reduce monocytic-biased cells, and the research suggests that understanding these different states and their responses to therapies could lead to better treatments for patients with CMML and similar conditions.
Article Synopsis
- * Research shows that patients with both ASXL1 and NRAS mutations experience shorter leukemia-free survival compared to those with only ASXL1 mutations, and similar results were observed in mouse models which also exhibited aggressive disease progression.
- * NA-AML cells (from the mouse model) overexpress immune checkpoint ligands and show high MEK/ERK signaling activity, but combining treatments targeting MEK and BET can improve immune responses and extend survival
Article Synopsis
- 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
Genomic Landscape and Risk Stratification in Chronic Myelomonocytic Leukemia.
Curr Hematol Malig Rep
June 2021
Article Synopsis
- Next-generation sequencing has advanced the understanding of chronic myelomonocytic leukemia (CMML), a type of cancer with complex clinical and genetic features, leading to improved precision in oncology.
- Research has identified that up to 90% of CMML patients have somatic gene mutations, particularly in genes like TET2, SRSF2, and ASXL1, which can significantly influence prognosis.
- The findings have prompted the creation of new prognostic models that take these mutations into account, suggesting that molecular profiling via next-generation sequencing should be standard practice for all patients with CMML.
Hypomethylating agents (HMAs) are widely used in the treatment of myelodysplastic syndromes (MDSs), yet identifying those patients unlikely to benefit remains challenging. We assessed response and overall survival (OS) in 247 patients molecularly profiled by next-generation sequencing (NGS) before first-line HMA therapy, and a subset of 108 patients were sequenced serially during treatment. The most common mutations included TP53 (33.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the effectiveness of hypomethylating agents in treating patients with chronic myelomonocytic leukaemia (CMML) by comparing their outcomes to those receiving other treatments, like hydroxyurea and intensive chemotherapy.
- Data was collected retrospectively from 949 patients across 38 centers in the USA and Europe between late 2017 and early 2019, focusing on overall survival and treatment progression.
- Findings showed that patients first treated with hypomethylating agents had a median overall survival of 20.7 months, which was better compared to 15.6 months for those treated with hydroxyurea, indicating potential benefits of hypomethylating agents in this patient group.
Article Synopsis
- The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are different types of blood cancers that have features similar to two other groups of blood disorders.
- These cancers include types like chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, recognized by health experts.
- New genetic studies are helping doctors understand how these cancers develop and how they can use this knowledge to make better treatment choices.
Article Synopsis
- Current treatments, including hypomethylating agents and allogeneic stem cell transplants, show poor outcomes for these patients, with transplants being the only potential cure.
- There is a need for new therapies that can better target TP53 mutations, particularly through direct targeting of the mutant protein and immunotherapies, which show the most promise.
Article Synopsis
- A large study involving 1,084 patients examined the role of TET2 mutations in chronic myelomonocytic leukemia (CMML), finding that these mutations often occur early and provide a fitness advantage to blood cell precursors.
- Out of the patients, 56% had TET2 mutations, with a significant portion being truncating, which affects the gene's catalytic function.
- Patient survival rates were notably better in those with TET2 mutations, especially if they had multiple mutations, and the presence of TET2 could improve outcomes for patients also carrying ASXL1 mutations.
Current status and new treatment approaches in TP53 mutated AML.
Best Pract Res Clin Haematol
June 2019
Article Synopsis
- Mutations in the TP53 gene, an essential tumor suppressor, are found in 5-10% of acute myeloid leukemia (AML) cases and are particularly common in therapy-related AML and complex karyotypes.
- *The presence of TP53 mutations is a strong negative prognostic factor, leading to poor responses to standard chemotherapy and rare long-term survival post-allogeneic stem cell transplant.
- *While hypomethylating agents have shown some improvement in treatment outcomes compared to traditional chemotherapy, there is a pressing need for innovative therapies due to the resistance associated with TP53 mutations.*
Current Management and Recent Advances in the Treatment of Chronic Myelomonocytic Leukemia.
Curr Treat Options Oncol
October 2018
Article Synopsis
- * While low-risk, asymptomatic patients may just be monitored, most will need treatment; participation in clinical trials for new therapies is encouraged due to limited effective options.
- * Allogeneic stem cell transplant is the only potential cure for intermediate- to high-risk patients, but many may not be candidates; hypomethylating agents are commonly used, along with supportive care to manage symptoms and improve quality of life.
Article Synopsis
- - The study focuses on improving treatment for locally-advanced non-small cell lung cancer (NSCLC) by reviewing the effectiveness of various chemo-radiotherapy regimens, as previous results from trials have been inconsistent and outcomes remain poor.
- - The researchers analyzed data from 28 trials with over 4,300 patients and found that the best treatment was concurrent, platinum-based chemo-radiotherapy, specifically 60 Gy in 30 fractions with cisplatin and vinblastine.
- - The findings provide clearer treatment recommendations than previous reviews and highlight that optimal regimens depend on outcome preferences and evidence quality criteria, suggesting a more tailored approach to NSCLC treatment.
Aggregating evidence about the positive and negative effects of treatments.
Artif Intell Med
November 2012
Article Synopsis
- Evidence-based decision making is essential in healthcare, and this paper introduces a new framework for analyzing clinical trials to compare treatments based on multiple outcome indicators.
- The framework evaluates arguments about treatment superiority or equivalence using evidence from various sources, like randomized trials and meta-analyses, while considering the importance of outcome indicators and the strength of evidence.
- In testing the framework against three clinical guidelines involving numerous pieces of evidence, the identified superior treatments aligned with the recommendations, demonstrating its effectiveness and applicability for real-world evidence aggregation.
Monoallelic silencing and haploinsufficiency in early murine intestinal neoplasms.
Proc Natl Acad Sci U S A
February 2012
Article Synopsis
- Many early adenomas in familial adenomatous polyposis and sporadic colon cancer lose normal function of the APC gene, primarily through genetic mechanisms in mouse and rat models.
- In the Pirc rat model, large colonic adenomas show no significant changes in genomic material and primarily lose heterozygosity on a specific chromosome arm, challenging traditional cancer development theories.
- Some tumors maintain heterozygosity of the APC gene without secondary mutations, suggesting two distinct pathways: one involves haploinsufficiency and the other leading to the silencing of the mutant allele through random processes.
Performing meta-analysis with incomplete statistical information in clinical trials.
BMC Med Res Methodol
August 2008
Article Synopsis
- The paper discusses challenges in meta-analysis when clinical trial data only includes mean values without standard error of mean (SEM) and presents two new methods to estimate missing SEMs for improved analysis.* -
- The two methods developed are the prognostic method, which predicts missing SEMs based on existing data, and the interval method, which establishes ranges expected to contain the missing SEMs.* -
- Testing these methods on clinical trials about drug effectiveness for lowering LDL cholesterol and intraocular pressure shows they can effectively approximate traditional meta-analysis results, even with incomplete data.*