Publications by authors named "Kristin Koenig"

Article Synopsis
  • The 2022 European LeukemiaNet (ELN) classification predicts outcomes for younger acute myeloid leukemia (AML) patients but was tested for those aged 60 and older receiving lower-intensity treatment (LIT), involving 595 patients with varying risk levels.
  • Results showed that while ELN risk is predictive of overall survival, it fails to distinguish between favorable and intermediate risks, prompting further exploration into adverse-risk patients' molecular abnormalities.
  • A new "Beat-AML" risk classification was developed, combining favorable and intermediate risks and integrating mutation scoring, leading to better survival predictions for older AML patients and aiding treatment decisions with clear risk group delineations.
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Background: Hypomethylating agents (HMAs) have shown efficacy in the treatment of hematological malignancies and are indicated for the treatment of chronic myelomonocytic leukemia (CMML). While the HMA decitabine, in its intravenous formulation, has been used since 2006 for the treatment of CMML, use of its oral formulation has been limited by poor bioavailability due to first-pass metabolism by the enzyme cytidine deaminase. The dose of intravenous decitabine is limited by toxicities such as cardiomyopathy and heart failure.

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New investigational combinations for higher-risk MDS.

Hematology Am Soc Hematol Educ Program

December 2022

Article Synopsis
  • * Treatment for MDS varies based on disease risk, with the Revised International Prognostic Scoring System used for evaluation; higher-risk patients typically receive hypomethylating agents and may qualify for stem cell transplants.
  • * Despite current treatments, the transformation to leukemia and patient outcomes remain significant challenges, prompting the development of novel combination therapies to enhance efficacy beyond standard single-agent HMA treatments.
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Aging is characterized by systemic declines in tissue and organ functions. Interventions that slow these declines represent promising therapeutics to protect against age-related disease and improve the quality of life. In this study, several interventions associated with lifespan extension in invertebrates or improvement of age-related disease were tested in mouse models to determine if they were effective in slowing tissue aging in a broad spectrum of functional assays.

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Venetoclax has efficacy in patients relapsing after B-cell receptor pathway inhibitors (BCRis); however, because of the risk of tumor lysis syndrome (TLS), a 5-week dose ramp-up is required to attain the target dose. Patients relapsing after BCRis frequently have proliferative disease, requiring a faster time to target dose than this scheme allows. This limitation can potentially be overcome with rapid dose escalation (RDE).

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Acute myeloid leukemia (AML) with myelodysplasia-related changes (AML-MRC) is a distinct biologic subtype of AML that represents 25-34% of all AML diagnoses and associates with especially inferior outcomes compared to non-MRC AML. Typically, patients with AML-MRC experience low remission rates following intensive chemotherapy and a median overall survival of merely 9-12 months. In light of these discouraging outcomes, it has become evident that more effective therapies are needed for patients with AML-MRC.

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The treatment of acute myeloid leukemia is evolving, with increased understanding of molecular pathogenesis allowing better risk stratification and development of new therapies. Tests to identify and drugs to target specific molecular abnormalities are improving remission rates and prolonging survival in patients with high-risk disease. Allogeneic hematopoietic stem cell transplantation remains an important curative therapy, with advances in donor availability and approaches to reduce transplant-related mortality making it applicable in many more patients.

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Purpose Of Review: Treatment of relapsed and refractory acute myeloid leukemia (AML) is still very challenging, with poor response rates and low chance for cure. This is especially true when treating patients who are elderly, have multiple comorbidities, or who are too unfit for traditional salvage chemotherapy regimens.

Recent Findings: Recently, advances in the treatment of relapsed/refractory AML utilizing novel chemotherapy combinations, hypomethylating, and targeted therapies have shown promising results.

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Unlabelled: Cellular senescence suppresses cancer by irreversibly arresting cell proliferation. Senescent cells acquire a proinflammatory senescence-associated secretory phenotype. Many genotoxic chemotherapies target proliferating cells nonspecifically, often with adverse reactions.

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