Impact of Sars-Cov-2 Infection in Acute Myeloid Leukemia Patients: Experience of the Pethema Registry

Abstract

SARS-CoV-2 infection can impact survival of patients with acute myeloid leukemia (AML). International experts recommend considering delaying or stopping AML treatment, test patients who need intensive induction and s prioritizing outpatient treatment. However there is little published evidence in AML.ObjectiveTo analyze the clinical futures and outcome of SARS-CoV-2 infection in AML patients.Methods and patientsObservational multicenter study between March and May 2020; 117 patients reported from 47 Spanish centers, but 13 had no PCR or antibody test documented, finally including 104 patients from 45 hospitals.ResultsThe median age was 68 years, men (56.7% vs 43.3%), and the median time from AML diagnosis to SARS-CoV-2 was 4 months. The mean of comorbidities was 1.2, high blood pressure (40.4%), heart disease (17.3%), diabetes (13.5%), smoking (8.8%), chronic obstructive pulmonary disease or emphysema (7.7%), renal failure (6.7%) and liver dysfunction (1.9%). Cytogenetic risk was low in 16.9%, intermediate in 57.1% and high in 26.0%; 55.7% had active disease, 39.2% complete remission and 5.1% partial response. 29.4% were off-therapy and 70.6% under antileukemic treatment at the time of SARS-CoV-2: induction chemotherapy (25.3%), hypomethylating (19.3%), clinical trial (17.0%), consolidation chemotherapy (14.8%), venetoclax (3.4%), FLT3 inhibitors (3.4%) and/or maintenance (1.1%). Overall 3.7% were newly diagnosed (no prior therapy), 77.8% had received one line of treatment, 14.8% two and 3.7% four. 15.4% had prior allogeneic transplantation.Only 4.0% of the patients were asymptomatic, while the main signs and symptoms were fever (77.8%), pneumonia (75.0%), cough (65.3%), dyspnea (52.0%), diarrhea (20.4%), nausea and/or vomiting (12.2%), rhinorrhea (10.2%) and headache (7.4%). Analytical parameters were: neutrophils 3112 cells/µL (1900-7300), lymphocytes 1090 cells/µL (1000-3000), interleukin 6 118 pg/mL (0-100), ferritin 4505 ng/mL (15-150) and D-dimer 2823 ng/mL (20-500), with liver enzymes altered in 23.9% of cases. 84.2% received specific treatment for coronavirus infection: chloroquine or hydroxychloroquine (82.2%), lopinavir/ritonavir (54.0%), corticosteroids (39.6%), azithromycin (33.0%), tocilizumab (15.8%), plasma convalescent (3.0%), clinical trial medication (3.0%), remdesivir (2.0%) and/or anakinra (1.0%).The course was mild in 14.7% (no hospitalization), moderate in 32.0% and severe in 53.3%. The implementation of intensive measures was assessed in 48.2%(14.9% admitted to the ICU and the remaining 33.3% rejected). The mean time to negativization was 20.5 days, duration of symptoms 17.6 days and the hospital stay 11.1 days. In 48.1% of the cases treatment for AML was maintained, in 26.6% delayed and in 25.3% modified due to coronavirus disease.47.5% died, establishing an association between mortality and age over 60 years (58.3% vs 36.4%, p=0.043), ≥2 lines of treatment (72.7% vs 44.3%, p=0.020), active disease (62.5% vs 29.4%, p=0.002) and pneumonia (61.2% versus 22.7%, p=0.002). Overall 47.5% overcame the infection, and in 5.0% SARS-CoV-2 genetic material was still detected at the time of analysis. A non-significant lower mortality rate was observed among: previous transplantation (45.7% vs 64.3%, p=0.19), neutrophil >1900 cells/µL (41.1% vs 60.0%, p=0.09), lymphocyte >1000 cells/µL (42.9% vs 63.6%, p = 0.09) and hydroxychloroquine/chloroquine plus azithromycin (35.3% vs 60.0%, p=0.10).ConclusionsSARS-CoV-2 infection produces high mortality among AML patients. Mortality was correlated with age, active disease and pneumonia.DisclosuresMartinez-Lopez:Janssen-cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Research Funding; Novartis: Consultancy; Janssen: Consultancy, Honoraria; Incyte: Consultancy, Research Funding.