Frontline acute myeloid leukemia (AML) treatment is determined by a combination of patient and genetic factors. This includes patient fitness (i.e., comorbidities that increase the risk of treatment-related mortality) and genetic characteristics, including cytogenetic events and gene mutations. In older unfit patients, the standard of care treatment is typically venetoclax (VEN) combined with hypomethylating agents (HMA). Recently, several drugs have been developed targeting specific genomic subgroups of AML patients, enabling individualized therapy. This has resulted in investigations of doublet and triplet combinations incorporating VEN aimed at overcoming known resistance mechanisms and improving outcomes in older patients with AML. These combinations include isocitrate dehydrogenase-1/2 (IDH1/2) inhibitors (i.e., ivosidenib and enasidenib), fms-like tyrosine kinase 3 (FLT3) inhibitors (i.e., gilteritinib), anti-CD47 antibodies (i.e., magrolimab), mouse double minute-2 (MDM2) inhibitors, and p53 reactivators (i.e., eprenetapopt). This review summarizes ongoing trials aimed at overcoming known VEN resistance mechanisms and improving outcomes beyond that observed with HMA + VEN combinations in the treatment of AML.
With rapid advancements in diagnosis and treatment of malignancies, the gap between generalists and subspecialists continues to widen, particularly in cancers like lymphoma where the spectrum of disease varies from indolent to rapidly progressive.Prior to establishing with a hematologist/oncologist, patients must be accurately and comprehensively diagnosed and managed for lymphoma in the generalist setting. In the following manuscript, we review the common clinical presentations in which should raise concern for lymphoma. We summarize the literature regarding the role of laboratory studies including complete blood count and peripheral blood flow cytometry, the recommendations for lymph node sampling, the role and selection of imaging modalities, and ideal patient monitoring for high-risk clinical syndromes that may be encountered in lymphoma.
Background: Asymptomatic neutropenia is a common hematology referral, though standardized reference ranges and published clinical outcomes are lacking.Methods: In our retrospective analysis, we evaluated demographics, laboratory, and clinical outcomes of adult patients referred to an academic hematology practice for evaluation of neutropenia from 2010 to 2018. Primary and secondary outcomes included incidence of hematologic disorders and rates of Duffy-null positivity by race, respectively. In a separate analysis, we reviewed absolute neutrophil count (ANC) reference ranges from publicly available Association of American Medical Colleges Medical School Member laboratory directories to assess institutional variations.Results: In total, 163 patients were included, with disproportionate number of Black patients referred compared to local demographics. Twenty-three percent of patients (n = 38) were found to have a clinically relevant hematologic outcome (mean ANC of 0.59 Â 10 9 /L), and only six were identified with ANC ≥1.0 Â 10 9 /L. Incidence of hematologic outcomes was lowest among Black patients (p = .05), and nearly all Blacks who underwent Duffy-null phenotype testing were positive (93%), compared to 50% of Whites (p = .04). In separate review of laboratory directories, we confirmed wide variation in ANC lower limit of normal (0.91-2.40 Â 10 9 /L). Conclusion:Hematologic disorders were rare in patients with mild neutropenia and among Blacks, highlighting the need to standardize hematological ranges representative of non-White communities.ethnic and racial minorities, health care, healthcare disparities, hematologic diseases, minority health, neutropenia, outcome assessment Novelty statementsWhat is the new aspect of your work?Through review of Association of American Medical Colleges Medical School Member laboratory directories, we found that the absolute neutrophil count lower limit of normal varies
e13122 Background: Breast cancer (BC) is the most common cancer in Women in the United States, it is the second most frequent cause of brain metastases (BM). Despite steady improvement in BC treatment (tx) and prognosis, BM continues to be an unmet need. With most BM patients excluded from clinical trials, the study of cohorts remains an important source of information regarding this aspect of the disease. We aim to characterize incidence, disease course, tx, and molecular profile of BM for BC subtypes. Methods: In this single-center retrospective analysis, we identified all adult patients (>18 years) diagnosed (dx) with BC as well as secondary malignant neoplasm of the brain from 1/1/15 to 10/1/22 using database query from EMR. Baseline characteristics were obtained through chart review. Molecular profiling was performed in a total of 41 patients, 8 of which was from brain tissue. Next generation sequencing (NGS) was the most used method. Results were generated using descriptive statistics. Results: We identified 304 BC patients with BM (median age = 60 years [range: 24 to 88]). Baseline characteristics are described in table 1. Hormone receptor positive/HER2-neu negative (HR+/HER2-) was the most commonly observed BC subtype (41.4%), and triple negative BC (TNBC) was the least frequent (16.8%). On primary tissue biopsy, five patients with recurrent BC had a subtype shift that differed from their initial disease: 2 patients with HR +/HER2 – BC subtype recurred with TNBC, 2 patients with a HR+/HER2- recurred with HR+/HER2+ BC, and 1 patient with TNBC at initial dx had their disease shift to HR+/HER 2- BC at first metastatic recurrence then back to TNBC 4 years after initial dx. NGS was available for 41 patients, with TP53, MSS, PIK3CA and ERBB2 being the most frequently observed mutations. On average, 3 lines of therapy were used before dx of BM. In the metastatic setting, capecitabine was one the most commonly used drugs. Targeted central nervous system (CNS) tx used in this study population include WBRT, SRS, SBRT and surgical resection. Conclusions: Studying patterns of disease presentation, progression during standard tx, and the molecular characteristics accompanying BM will enable us to develop more effective tx for patients. Our cohort includes a spectrum of BC subtypes and natural histories. Further characterization of this cohort with tx interactions, progression and survival timeline is ongoing and will be reported at the meeting. [Table: see text]
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