Impact of Sars-Cov-2 Infection in Acute Myeloid Leukemia Patients: Experience of the Pethema Registry
Authors: Martínez Pilar , Palanques Pastor Tomás , Lopez Lorenzo Jose Luiz , Cornago Navascués Javier , Rodriguez-Macías Gabriela , Cano Isabel , Arnan Sangerman Montserrat , Vidriales María-Belén , Algarra Jesús Lorenzo , Foncillas Maria Angeles , Herrera Puente Pilar , Botella Carmen , Vives Susana , Figuera Alvarez Angela , Cuevas Palomares Laida , Sobas Marta , Contento-Gonzalo Alejandro , Cuello Rebeca , Amutio Diez María Elena , De Miguel Maria Dunia , Navas Begoña , Bergua Burgues Juan Miguel , Bernal del Castillo Teresa , Mateos Rodríguez María Carmen , de Cabo López Erik , Franco Villegas Ana Carolina , García-Boyero Raimundo , Escolano Escobar Cristian , Seri Cristina , Cervero Carlos , Roldán Pérez Alicia , Hermosin Maria Lourdes , Cervera Marta , Olave María Teresa , Villafuerte Gutierrez Paola Sandra , De Laiglesia Almudena , Serrano Josefina , Najera Irazu María Josefa , Piñana Sanchez Jose Luis , Sanz Miguel Ángel , Martinez-Lopez Joaquin , Montesinos Pau 
Published: November 2020

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.
Objective
To analyze the clinical futures and outcome of SARS-CoV-2 infection in AML patients.
Methods and patients
Observational 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.
Results
The 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 &gt;1900 cells/µL (41.1% vs 60.0%, p=0.09), lymphocyte &gt;1000 cells/µL (42.9% vs 63.6%, p = 0.09) and hydroxychloroquine/chloroquine plus azithromycin (35.3% vs 60.0%, p=0.10).
Conclusions
SARS-CoV-2 infection produces high mortality among AML patients. Mortality was correlated with age, active disease and pneumonia.

Disclosures
Martinez-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.