Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy comprised of various cytogenetic and molecular abnormalities that has notoriously been difficult to treat with an overall poor prognosis. For decades, treatment options were limited to either intensive chemotherapy with anthracycline and cytarabine-based regimens (7 + 3) or lower intensity regimens including hypomethylating agents or low dose cytarabine, followed by either allogeneic stem cell transplant or consolidation chemotherapy. Fortunately, with the influx of rapidly evolving molecular technologies and new genetic understanding, the treatment landscape for AML has dramatically changed. Advances in the formulation and delivery of 7 + 3 with liposomal cytarabine and daunorubicin (Vyxeos) have improved overall survival in secondary AML. Increased understanding of the genetic underpinnings of AML has led to targeting actionable mutations such as FLT3, IDH1/2 and TP53, and BCL2 or hedgehog pathways in more frail populations. Antibody drug conjugates have resurfaced in the AML landscape and there have been numerous advances utilizing immunotherapies including immune checkpoint inhibitors, antibody-drug conjugates, bispecific T cell engager antibodies, chimeric antigen receptor (CAR)-T therapy and the development of AML vaccines. While there are dozens of ongoing studies and new drugs in the pipeline, this paper serves as a review of the advances achieved in the treatment of AML in the last several years and the most promising future avenues of advancement

OBJECTIVES 1) To examine the effects of a month-long nap regimen using one of two durations (45 min, or 2 hr) on nighttime sleep and waking function in a group of healthy older subjects. 2) To assess the degree to which healthy older individuals are willing/able to adhere to such napping regimens. DESIGN Three laboratory sessions, with 2-week at-home recording interspersed, using a between-subjects approach. SETTING The study was conducted in the Laboratory of Human Chronobiology at Weill Cornell Medical College and in subjects’ homes. PARTICIPANTS Twenty-two healthy men and women aged 50–88 years (mean = 70y). MEASUREMENTS Polysomnography (sleep EEG), actigraphy, sleep diaries, neurobehavioral performance, sleep latency tests. RESULTS With the exception of compliance to the protocol, there were few differences between Short and Long nap conditions. Napping had no negative impact on subsequent nighttime sleep quality or duration, resulting in a significant increase in 24-hour sleep amounts. Such increased sleep was associated with enhanced cognitive performance, but had no impact on simple reaction time. Subjects were generally able to comply better with the 45-minute than the 2-hour nap regimen. CONCLUSION A month-long, daily nap regimen may enhance waking function without negatively impacting nighttime sleep. Using 2-hour naps in such a regimen is unlikely to meet with acceptable compliance; a regimen of daily 1-hour naps may be more desireable for both effectiveness and compliance.

The transformation of acute promyelocytic leukemia (APL) from an often fatal to highly curable cancer with long-term survival exceeding 90% is one of the greatest and most inspiring successes in oncology. A deeper understanding of the pathogenesis of APL heralded the introduction of highly effective therapies targeting the mutant protein that drives the disease, leading to the chemotherapy-free approach to cure almost all patients. In this review, we discuss the paradigm of treatment of APL in 2023, reinforce the high risk of early death without prompt initiation of treatment at first clinical suspicion, and dedicate a special focus to novel agents and future directions to improve cure rates and quality of life in patients affected by APL.

(1) Background: the SARS-CoV-2 (COVID-19) pandemic continues, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease with poorer outcomes. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 (“Omicron”) COVID-19 variant wave. (2) Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida, USA, from 1 December 2021 through 30 April 2022. We assessed demographic variables and quality outcomes among patients. (3) Results: 1031 patients and 18 providers were retrospectively analyzed. 90 patients tested positive for COVID-19 (8.73%), while 6 providers tested positive (33.3%) (p = 0.038). There were 4 (10.3%) COVID-19-related deaths (and another outside our study timeframe) and 39 non-COVID-19-related deaths (89.7%) in the patient population (p = 0.77). COVID-19 accounted for 4.44% of our clinic’s total mortality, and delayed care in 64.4% of patients. (4) Conclusions: The prevalence of COVID-19 positivity in our patient cohort mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. Almost two-thirds of patients experienced a cancer treatment delay, significantly impacting oncologic care.

We tested whether a single nucleotide polymorphism (SNP) that affects splicing of CD33 predicted response to treatment in adults with acute myeloid leukemia (AML) who received the novel CD33 antibody-drug conjugate SGN-CD33A. This genotype, for the CD33 splice site SNP rs12459419, was not associated with clinical response (30% CR/CRi in both groups), event-free survival, or overall survival.

Myelodysplastic syndromes (MDS) encompass a variety of myeloid neoplasms characterized by ineffective hematopoiesis. The interaction of abnormal clonal hematopoiesis and changes in the bone marrow microenvironment propagate abnormal clones. Advances in next generation sequencing has identified over 100 somatic mutations, but despite deepened understanding of the genetics of MDS, therapeutic discoveries have remained limited. To date, only five drugs have been approved for MDS: Azacitidine, Decitabine, Lenalidomide, Luspatercept, and oral Decitabine with Cedazuridine. Current strategies for low-risk MDS continue to focus on symptomatic management and correction of cytopenias, while treatment for high-risk MDS focuses on delaying progression of disease and improving survival. In this review we discuss some of the challenges in developing pre-clinical models of MDS in which to test therapeutics, the advances that have been made, and promising novel therapeutics in the pipeline.

BACKGROUND/INTRODUCTION: We tested whether a single nucleotide polymorphism (SNP) that affects splicing of CD33 predicted response to treatment in adults with acute myeloid leukemia (AML) who received the novel CD33 antibody-drug conjugate SGN-CD33A. METHODS: Twenty patients with CD33+ AML who received SGNCD33A either as monotherapy (10-50 mcg/kg) or in combination with hypomethylating agents (10 mcg/kg SGN-CD33A and standard doses of hypomethylating agent) were tested for the CD33 SNP genotype (rs12459419) using TaqMan SNP genotyping (Applied Biosystems, CA). Clinical characteristics of disease, prior treatments, and outcome data were collected and analyzed for association of the SNP genotype with response rate, the primary objective. Event-free and overall survivals were secondary objectives assessed by the Kaplan-Meier estimator. We included adults with de novo and secondary AML who had either experienced disease relapse or declined intensive chemotherapy. RESULTS: Compared with patients in previous studies, our patients were generally older and were not treated in combination with chemotherapy. Notably, CD33 SNPs are germline mutations, so these could result in different expression of CD33 in off target tissue. An alternative hypothesis, therefore, is that increased toxicity in the CC genotype would offset the drugs' benefit; however, neither our study nor the other adult study showed any difference in response rates between genotypes. This lack of any benefit for the CC genotype in adult AML suggests that age-related or other biological differences between adult and pediatric AML may explain disparate results between these groups. CONCLUSION: This genotype, for the CD33 splice site SNP rs12459419, was not associated with clinical response (30% CR/CRi in both groups), event-free survival, or overall survival.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy primarily affecting older adults. Historically, the highest rates of response have been achieved with intensive induction chemotherapy; however, a significant portion of older or unfit adults with AML are unable to tolerate intensive therapy or have chemotherapy-resistant disease, creating a large need for active and less intensive treatment strategies. Glasdegib, an oral inhibitor of the transmembrane protein Smoothened (SMO) involved in the Hedgehog (Hh) signaling pathway, was approved in 2018 for older or unfit adults with AML and attained a role in clinical practice after showing an overall survival (OS) advantage when combined with the established agent low-dose cytarabine (LDAC). Since that time, however, several other highly active lower intensity therapies such as venetoclax plus a hypomethylating agent (HMA) have garnered a dominant role in the treatment of this patient population. In this review, we summarize the role of glasdegib in the current treatment landscape of newly diagnosed AML and discuss ongoing investigations into its role in novel combination therapies.