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.
View Article and Find Full Text PDFHematology Am Soc Hematol Educ Program
December 2022
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.
View Article and Find Full Text PDFVenetoclax 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).
View Article and Find Full Text PDFAcute 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.
View Article and Find Full Text PDFAm Soc Clin Oncol Educ Book
March 2020
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.
View Article and Find Full Text PDFPurpose 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.
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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