Publications by authors named "Courtney D Dinardo"
Delayed hemolytic transfusion reaction (DHTR) poses a significant challenge in patients receiving blood transfusions. This case report highlights the complexities of managing DHTR in a newly diagnosed chronic myelomonocytic leukemia (CMML) patient with clinically significant JKa and little c antibodies during induction chemotherapy. A 46-year-old woman with CMML-2 who presented for induction chemotherapy was found to have hemolytic anemia.
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Mutation- and MRD-informed treatments for transplant-ineligible patients.
Hematology Am Soc Hematol Educ Program
December 2024
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The outcomes of patients with acute myeloid leukemia (AML) and bone marrow fibrosis (MF) are not well defined. The study objectives were to evaluate the degrees of MF in AML, and corresponding response rates and outcomes. We performed a retrospective review of 2302 patients with AML.
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- * The study reveals that RAS mutations transform specific blood cell progenitors (granulocyte-monocyte progenitors) that have already acquired other mutations, suggesting advanced leukemia can arise from different cell types than initial clones.
- * RAS-mutant leukemia stem cells show resistance to the treatment drug venetoclax due to changes in gene expression, leading to worse treatment responses and relapses characterized by monocytic features, highlighting the impact of genetic drivers on therapy effectiveness.
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Malignancies are reliant on glutamine as an energy source and a facilitator of aberrant DNA methylation. We demonstrate preclinical synergy of telaglenastat (CB-839), a selective glutaminase inhibitor, combined with azacytidine (AZA), followed by a single-arm, open-label, phase 1b/2 study in persons with advanced myelodysplastic syndrome (MDS). The dual primary endpoints evaluated clinical activity, safety and tolerability; secondary endpoints evaluated pharmacokinetics, pharmacodynamics, overall survival, event-free survival and duration of response.
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- Advances in understanding the molecular pathobiology of acute myeloid leukemia (AML) have led to the development of twelve new targeted therapies approved since 2017, including various inhibitors and antibody-drug conjugates.
- These therapies, such as venetoclax and FLT3 inhibitors, aim to treat specific AML subsets and improve patient outcomes through precision medicine.
- Successful treatment of AML requires specialized expertise, access to diverse therapies, and a strong supportive care system, alongside ongoing research into new treatment options and combinations.
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- Aberrant expression of HOX and MEIS1 family genes in certain leukemias disrupts normal blood cell differentiation and contributes to leukemia development.
- Menin inhibitors can target the interaction between KMT2A and menin, reducing the abnormal expression of key factors and promoting differentiation in these leukemias.
- A collaborative effort among pediatric and adult specialists aims to advance menin inhibitors in treatment, offering a comprehensive overview of clinical trials and advocating for inclusive trial designs for youth.
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- The European LeukemiaNet (ELN) previously created genetic risk classifications using data from younger adults who underwent intensive chemotherapy.
- New research has emerged analyzing patients who receive less-intensive therapies, highlighting the need for tailored classifications.
- This has led to a proposal for a new ELN genetic risk classification specifically designed for patients undergoing these alternative treatment options.
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- The European LeukemiaNet (ELN) classification systems for acute myeloid leukemia (AML) are based on chemotherapy responses and may not effectively predict outcomes for older patients receiving venetoclax-azacitidine.
- A pooled analysis from the phase 3 VIALE-A trial revealed that most patients were classified with adverse-risk AML, yet these classifications did not correlate well with survival outcomes for those treated with venetoclax-azacitidine.
- New molecular signatures based on mutations in TP53, FLT3-ITD, NRAS, and KRAS identified three distinct patient benefit groups, each with significantly different median overall survival times.
Clonal hematopoiesis: malignant implications, extrahematologic manifestations, and management.
Clin Adv Hematol Oncol
September 2024
As individuals age, their hematopoietic stem cells can sporadically acquire genetic mutations, known as clonal hematopoiesis. Although most of these genomic aberrations are of little consequence, particular changes in certain contexts can lead to the development of hematologic malignancies, such as myelodysplastic syndromes and acute myeloid leukemia. Owing to its pervasive extrahematologic interactions, clonal hematopoiesis is a recognized risk factor for and is causally implicated in the development of several chronic diseases of aging and/or inflammation, such as atherosclerotic cardiovascular disease.
View Article and Find Full Text PDFBackground: Mouse double minute-2 homolog (MDM2) plays a key role in downregulating p53 activity in hematologic malignancies, and its overexpression is associated with poor outcomes.
Methods: This phase 1 study assessed the safety and efficacy of different dosing regimens of the MDM2 inhibitor milademetan as monotherapy and in combination with azacitidine (AZA) in patients with relapsed or refractory acute myeloid leukemia or high-risk myelodysplastic syndromes.
Results: Seventy-four patients (monotherapy, n = 57; milademetan-AZA combination, n = 17) were treated.