Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. Adults age ≥18 years with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in this international phase 3 randomized double-blind placebo-controlled trial. Patients (N = 211) were randomized 2:1 to venetoclax (n = 143) or placebo (n = 68) in 28-day cycles, plus low-dose cytarabine (LDAC) on days 1 to 10. Primary end point was overall survival (OS); secondary end points included response rate, transfusion independence, and event-free survival. Median age was 76 years (range, 36-93 years), 38% had secondary AML, and 20% had received prior hypomethylating agent treatment. Planned primary analysis showed a 25% reduction in risk of death with venetoclax plus LDAC vs LDAC alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.52-1.07; P = .11), although not statistically significant; median OS was 7.2 vs 4.1 months, respectively. Unplanned analysis with additional 6-month follow-up demonstrated median OS of 8.4 months for the venetoclax arm (HR, 0.70; 95% CI, 0.50-0.98; P = .04). Complete remission (CR) plus CR with incomplete blood count recovery rates were 48% and 13% for venetoclax plus LDAC and LDAC alone, respectively. Key grade ≥3 adverse events (venetoclax vs LDAC alone) were febrile neutropenia (32% vs 29%), neutropenia (47% vs 16%), and thrombocytopenia (45% vs 37%). Venetoclax plus LDAC demonstrates clinically meaningful improvement in remission rate and OS vs LDAC alone, with a manageable safety profile. Results confirm venetoclax plus LDAC as an important frontline treatment for AML patients unfit for intensive chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03069352.

Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 virus and has been declared a pandemic on the 9th of March by the WHO. A hallmark of COVID-19 management is supportive care and there is still no convincing evidence for a treatment which will reduce mortality. Severe COVID-19-associated sepsis characterized by acute respiratory distress syndrome (ARDS), secondary bacterial pneumonias, thrombotic complications, myocarditis, and gastrointestinal involvement are more prevalent in those with comorbidities such as hypertension, diabetes, cardiac disease, cancer and age >70 years. 1,2 There is a paucity of data on COVID-19's impact on bone marrow transplant patients. Herein we reflect on the course of seven bone marrow transplant recipients in Birmingham Heartlands Hospital who have been found positive for SARS-CoV-2 RNA on real time polymerase chain reaction (RT-PCR) from nasopharyngeal swabs done in the context of symptoms (fever, cough, dyspnoea, and fatigue) or inpatient contact. The median age was 61 years (range 40-74). Out of these, five (71%) were female and two (29%) were male. The median time from stem cell infusion to the diagnosis of SARS-CoV-2 virus was 61 days (range 7-343). Patients were screened for SARS-CoV-2 via an RT-PCR-based technique.

COVID-19 has been declared as a global pandemic, affecting more than a hundred countries in a matter of weeks and claiming many lives up until now. The clinical spectrum ranges from asymptomatic carriers to symptomatic patients with mild symptoms and patients requiring intensive care unit (ICU) admission at the other extreme. Variable clinical presentations have been reported, most commonly involving the chest with shortness of breath being most common. Less commonly it has also been reported with gastrointestinal and neurological manifestations. Haematological manifestations in symptomatic COVID-19 patients include severe leukopenia with lymphopenia and mild thrombocytopenia with platelet counts ranging between 100-150 9 10 9 /l. [1][2][3][4] We hereby report a case series of three patients; the first two patients presented with severe thrombocytopenia and were subsequently found to be COVID-19positive. The third case emphasises the presentation of severe thrombocytopenia as a marker of severity and poor prognosis in symptomatic COVID-19 patients.

VIALE-C compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine (+LDAC) in patients with untreated AML ineligible for intensive chemotherapy. Overall, 211 patients were enrolled (n = 143, venetoclax; n = 68, placebo). At the primary analysis, the study did not meet its primary endpoint of a statistically significant improvement in overall survival (OS), however, ~60% of patients had been on study for ≤6-months. Here, we present an additional 6-months of follow-up of VIALE-C (median follow-up 17.5 months; range 0.1–23.5). Median OS was (venetoclax +LDAC vs. placebo +LDAC) 8.4 vs. 4.1 months (HR = 0.70, 95% CI 0.50,0.99; P = 0.040); a 30% reduction in the risk of death with venetoclax. Complete response (CR)/CR with incomplete hematologic recovery (CRi) rates were 48.3% vs. 13.2%. Transfusion independence rates (RBC) were 43% vs.19% and median event-free survival was 4.9 vs. 2.1 months (HR = 0.61; 95% CI 0.44,0.84; P = 0.002). These results represent improved efficacy over the primary analysis. Incidence of grade ≥3 adverse events were similar between study arms and overall safety profiles were comparable to the primary analysis. These data support venetoclax +LDAC as a frontline treatment option for patients with AML ineligible for intensive chemotherapy.This trial was registered at www.clinicaltrials.gov as #NCT03069352.