Pilar Martínez, MD1*, Tomás Palanques Pastor2*, Jose Luiz Lopez Lorenzo, MD3*, Javier Cornago Navascués, MD4*, Gabriela Rodriguez-Macías, MD5*, Isabel Cano, MD6*, Montserrat Arnan Sangerman, MD, PhD7*, María-Belén Vidriales, MD, PhD8*, Jesús Lorenzo Algarra9*, Maria Angeles Foncillas10*, Pilar Herrera Puente11*, Carmen Botella12*, Susana Vives, MD13*, Angela Figuera Alvarez, MD, PhD14*, Laida Cuevas Palomares15*, Marta Sobas, MD PhD16*, Alejandro Contento-Gonzalo, MD17*, Rebeca Cuello, MD18*, María Elena Amutio Diez, MD19*, Maria Dunia De Miguel, MD20*, Begoña Navas, MD21*, Juan Miguel Bergua Burgues, MD22*, Teresa Bernal del Castillo, MD, PhD23*, María Carmen Mateos Rodríguez, MD24*, Erik de Cabo López, MD25*, Ana Carolina Franco Villegas, MD26*, Raimundo García-Boyero, MD27*, Cristian Escolano Escobar, MD28*, Cristina Seri, MD29*, Carlos Cervero, MD30*, Alicia Roldán Pérez31*, Maria Lourdes Hermosin, MD32*, Marta Cervera, MD33*, María Teresa Olave, MD34*, Paola Sandra Villafuerte Gutierrez, MD35*, Almudena De Laiglesia, MD36*, Josefina Serrano, MD37*, María Josefa Najera Irazu, MD38*, Jose Luis Piñana Sanchez39*, Miguel Ángel Sanz, MD39, Joaquin Martinez-Lopez, MD40* and Pau Montesinos, MD, PhD41*
1Hematology Department, Hospital Universitario 12 de Octubre,, Madrid, Spain
2Pharmacy department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
3Servicio de Hematología y Hemoterapia, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
4Hematology and hemotherapy department, Hospital Universitario Fundación Jiménez Díaz, Valencia, Spain
5Hematology and hemotherapy department, Hospital General Universitario Gregorio Marañón, Madrid, Spain
6Hospital Universitario y Politécnico La Fe, Valencia, Spain
7Clinic hematology department, Instituto Catalán de Oncología, Hospitalet del Llobregat, Spain
8Hematology department, Hospital Universitario de Salamanca, Salamanca, Salamanca, Spain
9Hematology department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain
10Hematology Department, Hospital Universitario Infanta Leonor, Madrid, Spain
11Hematology department, Hospital Ramón y Cajal, Madrid, Spain
12Hematology department, Hospital General Universitario de Alicante, Alicante, Spain
13Hematology Department, ICO - Hospital Germans Trias i Pujol, Badalona, Spain
14Hematology and hemotherapy department, Hospital Universitario de la Princesa, Madrid, Spain
15Hematology and hemotherapy department, Hospital Txagorritxu, Vitoria, Spain
16Department of Hematology, Wroclaw Medical University, Wroclaw, Poland
17Hematology and hemotherapy department, Hospital Regional Universitario de Málaga, Málaga, Spain
18Hematology and hemotherapy department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
19Hematology and hemotherapy department, Hospital Universitario de Cruces, Barakaldo, Spain
20Hematology department, Hospital Universitario de Guadalajara, Guadalajara, Spain
21Hematology and hemotherapy department, Hospital Universitario HLA Moncloa, Madrid, Spain
22Hematology and hemotherapy department, Hospital San Pedro de Alcántara, Cáceres, Spain
23Hospital Universitario Central Asturias, ISPA, IUOPA, Oviedo, Spain
24Hematology department, Complejo Hospitalario de Navarra, Pamplona, Spain
25Hematology and hemotherapy department, Hospital El Bierzo, Ponferrada, Spain
26Oncology and clinic hematology department, Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
27Hematology and hemotherapy department, Hospital Universitario General de Castellón, Castellón de la Plana, Spain
28Hematology and hemotherapy department, Hospital Universitario de Getafe, Getafe, Spain
29Hematology and hemotherapy department, Hospital Central de la Defensa Gómez Ulla, Madrid, Spain
30Hematology department, Hospital Virgen de la Luz, Cuenca, Spain
31Hematology and hemotherapy department, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, Spain
32Jerez de la Frontera Hospital, JEREZ DE LA FRONTERA, Spain
33ICO-Hospital Joan XXIII, Tarragona, Spain
34Hematology and hemotherapy department, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain
35Hematology and hemotherapy department, Hospital Universitario Príncipe de Asturias, Alcala De Henares, Spain
36Hematology and hemotherapy department, Hospital Universitario Puerta De Hierro, Majadahonda, Spain
37Clinical Hematology, Hospital Universitario Reina Sofía, Córdoba, Spain
38Hematology department, Hospital San Pedro, Logroño, Spain
39Hematology and hemotherapy department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
40Hematology and hemotherapy department, Hospital Universitario 12 De Octubre, Madrid, Spain
41Hematology Department, Hospital Universitario La Fe de Valencia,, Valencia, Spain, Spain
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 >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).
Conclusions
SARS-CoV-2 infection produces high mortality among AML patients. Mortality was correlated with age, active disease and pneumonia.
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