The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine.

The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 is a global public health crisis. Multiple observations indicate poorer post-infection outcomes for patients with cancer than for the general population. Herein, we highlight the challenges in caring for patients with acute leukaemias and myeloid neoplasms amid the COVID-19 pandemic. We summarise key changes related to service allocation, clinical and supportive care, clinical trial participation, and ethical considerations regarding the use of lifesaving measures for these patients. We recognise that these recommendations might be more applicable to high-income countries and might not be generalisable because of regional differences in health-care infrastructure, individual circumstances, and a complex and highly fluid health-care environment. Despite these limitations, we aim to provide a general framework for the care of patients with acute leukaemias and myeloid neoplasms during the COVID-19 pandemic on the basis of recommendations from international experts.

7082 Background: Research interest in small cell lung cancer (SCLC) has waned over the past 10 years due to the lack of significant therapeutic advances and a presumed decline in the incidence of SCLC. Methods: We analyzed data on all patients with primary bronchogenic carcinoma registered in the national SEER database from 1973–2002. To identify temporal trends, the study period was divided into three decades: 1973–1982 (D1), 1983–1992 (D2), and 1993–2002 (D3). Results: Of 318,584 eligible patients, 59,704 (18.7%) had SCLC. The proportional incidence of SCLC relative to non-SCLC was higher in Caucasians than African-Americans (19.6% vs 13.9%), women vs men (21% vs 17.4%), and patients ≥ 50 yrs old vs < 50 yrs old (18.9% vs 16%). By decade, the proportional incidence of SCLC was: D1, 18.4%; D2, 19.8%; D3, 17.9%. The overall incidence rates for both SCLC and non-SCLC initially rose and then declined during the study period. The incidence rates for SCLC were similar in both Caucasians and African-Americans throughout the study period, while those for non-SCLC were significantly higher in African-Americans. The gap between incidence rates in men and women has narrowed to a similar degree for both SCLC (M/F: D1, 2.6/1 to D3 1.4/1) and NSCLC (M/F: D1, 3.3/1 to D3, 1.7/1). Only 0.8% of SCLC patients underwent surgical resection from 1988–2002. The use of radiotherapy decreased during the study period (D1, 53% to D3, 43%) with greater use in younger patients and African-Americans. Stage-specific 2- and 5-year survival rates for SCLC improved over time (regional 2-yr/5-yr: D1, 15%/6.8% to D3, 22%/11%; distant 2-yr/5-yr: D1, 3.4%/1.3% to D3, 5.6%/1.9%). In multivariate analysis, significant favorable prognostic factors included: younger age, Caucasian race, female gender, limited stage, and later year of diagnosis. Conclusions: The proportional incidence of SCLC has declined only slightly over the past three decades. While overall survival has modestly improved, SCLC remains a major public health problem. No significant financial relationships to disclose.

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Hypomethylating agents (HMAs) in combination with venetoclax have been widely adopted as the standard of care for patients who cannot tolerate induction chemotherapy and for patients who have relapsed/refractory (R/R) acute myeloid leukemia (AML). This study retrospectively analyzed the outcomes of all patients with AML (n = 65) or myelodysplastic syndrome (n = 7) who received the combination of HMA and venetoclax at our institution. Outcomes measured included complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates, duration of response (DOR), and overall survival (OS). Patient mutational profiles and transfusion requirements were also assessed. Of 26 newly diagnosed AML patients, the CR/CRi rate was 53.8%. The median DOR and OS were 6.9 months and not reached, respectively. Of 39 R/R AML patients, the CR/CRi rate was 38.5%. The median DOR and OS were both 8.1 months. Responders to HMA and venetoclax were enriched for TET2, IDH1, and IDH2 mutations, while nonresponders were associated with FLT3 and RAS mutations. Adaptive resistance was observed through various mechanisms including acquired RAS pathway mutations. Of transfusion-dependent patients, 12.2% and 15.2% achieved red blood cell (RBC) and platelet transfusion independence, respectively, while 44.8% and 35.1% of RBC and platelet transfusion independent patients, respectively, became transfusion dependent. In total 59.1% of patients developed a ≥grade 3 infection and 46.5% neutropenic fever. HMA + venetoclax can lead to impressive response rates with moderately durable remissions and survival. However, the benefits of this combination are diminished by the significant toxicities from infection, persistent cytopenias, and transfusion requirements.

Pain and anxiety are closely associated with bone marrow aspirates and biopsies. To determine whether hypnosis administered concurrently with the procedure can ameliorate these morbidities, the authors randomly assigned 80 cancer patients undergoing bone marrow aspirates and biopsies to either hypnosis or standard of care. The hypnosis intervention reduced the anxiety associated with procedure, but the difference in pain scores between the two groups was not statistically significant. The authors conclude that brief hypnosis concurrently administered reduces patient anxiety during bone marrow aspirates and biopsies but may not adequately control pain. The authors explain this latter finding as indicating that the sensory component of a patient's pain experience may be of lesser importance than the affective component. The authors describe future studies to clarify their results and address the limitations of this study.

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Myelodysplastic syndromes (MDS) represent a clonal hematopoietic stem cell disorder characterized by morphologic features of dyspoiesis, a hyperproliferative bone marrow, and one or more peripheral blood cytopenias. In patients classified according to the Revised International Prognostic Scoring System (R-IPSS) with intermediate or higher-risk disease, there is an increased risk of death due to progressive bone marrow failure or transformation to acute myeloid leukemia (AML). Azacitidine was the first DNA hypomethylating agent approved by the United States (US) Food and Drug Administration (FDA) for the treatment of MDS and the only therapy that has demonstrated a significant survival benefit over conventional care regimens (CCRs) in patients with intermediate or higher-risk disease. Prolonged survival is independent of achieving a complete remission. Azacitidine has been used in older patients with both clinical and hematological improvement as well as an acceptable side effect profile. The most common adverse effect is myelosuppression. These findings support the use of azacitidine as an effective treatment in older patients with higher-risk MDS.