Characteristics, clinical outcomes, and risk factors of SARS-COV-2 infection in adult acute myeloid leukemia patients: experience of the PETHEMA group

Palanques-Pastor, Tomás; Megías‐Vericat, Juan Eduardo; Martı́nez, Pilar; Lorenzo, José Luis López; Navascués, Javier Cornago; Macias, Gabriela Rodríguez; Cano, Isabel; Sangerman, Montserrat Arnán; Vicente, María Belén Vidriales; Algarra, Jesús Lorenzo; Foncillas, María Ángeles; Herrera, Pilar; Prieto, Carmen Botella; Vives, Susana; Álvarez, Ángela Figuera; Palomares, Laida Cuevas; Sobas, Marta; Gonzalo, Alejandro; García, Rebeca Cuello; Díez, María Elena Amutio; Llorente, D. de Miguel; Elorza, Begoña Navas; Burgues, Juan Miguel Bergua; Bernal, Teresa; Rodriguez, María Carmen Mateos; López, Erik de Cabo; Villegas, A; Boyero, Raimundo García; Escobar, Cristián Escolano; Merino, Cristina Seri; Cerveró, Carlos; Pérez, Alicia Roldán; Ramos, Lourdes; Calvo, M. Cervera; Olave, María T.; Gutiérrez, Paola Villafuerte; Laiglesiai, Almudena de; Serrano, Josefina; Irazu, María Josefa Najera; Piñana, José Luís; Sanz, Miguel Á.; Martínez‐López, Joaquin; Montesinos, Pau

doi:10.1080/10428194.2021.1948031

Cited by 28 publications

(33 citation statements)

References 35 publications

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“…In a similar Italian study, four factor were associated with worse survival: older age (HR 1.06, 95% CI 0.60–1.24); progressive disease status (HR 2.10, 95% CI 1.41–3.12); type of HM (AML, indolent or aggressive non-Hodgkin lymphoma, plasma cell neoplasm), where AML had the highest HR of 3.49 (95% CI 1.56–7.81); and severe or critical COVID-19 (HR 4.08, 95% CI 2.73–6.09) [ 4 ]. Similarly, a subsequent PETHEMA study, focusing on AML, confirmed that SARS-CoV-2 infection confers high mortality among these patients and 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% vs. 22.7%, p 0.002) [ 17 ]. The EPICOVIDEHA survey also confirmed these results by showing that age, active haematological disease, AML, and MDS are the categories to be considered at greatest risk of death [ 16 ].…”

Section: Epidemiologymentioning

confidence: 99%

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

et al. 2022

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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus that spread worldwide from 2019 causing the Coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 infection is characterised by an initial viral phase followed in some patients by a severe inflammatory phase. Importantly, immunocompromised patients may have a prolonged viral phase, shedding infectious viral particles for months, and absent or dysfunctional inflammatory phase. Among haematological patients, COVID-19 has been associated with high mortality rate in acute leukaemia, high risk-myelodysplastic syndromes, and after haematopoietic cell transplant and chimeric-antigen-receptor-T therapies. The clinical symptoms and signs were similar to that reported for the overall population, but the severity and outcome were worse. The deferral of immunodepleting cellular therapy treatments is recommended for SARS-CoV-2 positive patient, while in the other at-risk cases, the haematological treatment decisions must be weighed between individual risks and benefits. The gold standard for the diagnosis is the detection of viral RNA by nucleic acid testing on nasopharyngeal-swabbed sample, which provides high sensitivity and specificity; while rapid antigen tests have a lower sensitivity, especially in asymptomatic patients. The prevention of SARS-CoV-2 infection is based on strict infection control measures recommended for aerosol-droplet-and-contact transmission. Vaccinations against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalisation and deaths due to severe COVID-19 disease in the general population, but immunosuppressed/haematology patients may have lower sero-responsiveness to vaccinations. Moreover, the recent emergence of new variants may require vaccine modifications and strategies to improve efficacy in these vulnerable patients. Beyond supportive care, the specific treatment is directed at viral replication control (antivirals, anti-spike monoclonal antibodies) and, in patients who need it, to the control of inflammation (dexamethasone, anti-Il-6 agents, and others). However, the benefit of all these various prophylactic and therapeutic treatments in haematology patients deserves further studies.

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Section: Epidemiologymentioning

confidence: 99%

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

et al. 2022

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“…Table 1 summarizes the available data of clinical manifestations by HM type. Within HM patients, those with acute myeloid leukemia and myelodysplastic syndrome are repeatedly shown to suffer from more severe disease, protracted clinical courses, and high rates of ICU admissions [23,24]. The reported rates of severe COVID-19 in this group are around 40% in different studies with mortality occurring in up to 35-54% of cases [23][24][25][26].…”

Section: Resultsmentioning

confidence: 99%

“…Within HM patients, those with acute myeloid leukemia and myelodysplastic syndrome are repeatedly shown to suffer from more severe disease, protracted clinical courses, and high rates of ICU admissions [23,24]. The reported rates of severe COVID-19 in this group are around 40% in different studies with mortality occurring in up to 35-54% of cases [23][24][25][26]. Acute lymphoblastic leukemia was also associated with high rates of symptomatic disease (75%), oxygen support (38%), ICU admission (21%), and mortality (33%) [27].…”

Section: Resultsmentioning

confidence: 99%

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

et al. 2022

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Background: The clinical presentation of coronavirus disease 19 (COVID-19) is the result of intricate interactions between the novel coronavirus and the immune system. In patients with hematologic malignancies (HM), these interactions dramatically change the clinical course and outcomes of COVID-19. Summary: Patients with HM and COVID-19 are at an increased risk for prolonged viral shedding, more protracted and severe presentation, and death, even when compared to other immunocompromised hosts. HM (e.g., multiple myeloma, chronic lymphocytic leukemia) and anticancer treatments (e.g., anti-CD20 agents) that impair humoral immunity markedly increase the risk of severe COVID-19 as well as protracted viral shedding and possibly longer infectivity. Cytokine release syndrome (CRS) is an important player in the pathophysiology of severe and fatal COVID-19. Treatments targeting specific cytokines involved in CRS such as interleukin-6 and Janus kinase have proven beneficial in COVID-19 patients but were not assessed specifically in HM patients. Although neutropenia (as well as neutrophilia) was associated with increased COVID-19 mortality, granulocyte colony-stimulating factors were not beneficial in patients with COVID-19 and may have been associated with worse outcomes. Decreased levels of T lymphocytes and especially decreased CD4+ counts, and depletion of CD8+ lymphocytes, are a hallmark of severe COVID-19, and even more so among patients with HM, underlying the important role of T-helper dysfunction in severe COVID-19. In HM patients with intact cellular immunity, robust T-cell responses may compensate for an impaired humoral immune system. Further prospective studies are needed to evaluate the mechanisms of severe COVID-19 among patients with HM and assess the efficacy of new immunomodulating COVID-19 treatments in this population. Key Messages: Understanding the immunopathology of COVID-19 has greatly benefited from the previous research in patients with HM. So far, no COVID-19 treatments were properly evaluated in patients with HM. Patients with HM should be included in future RCTs assessing treatments for COVID-19.

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“…It has been suggested that SARS-CoV-2 infection is associated with higher rates of morbidity and mortality in patients with hematological malignancies and other cancers [ 2 , 3 ]. However, the evidence is sparse for acute myeloid leukemia (AML) [ 4 , ].…”

mentioning

confidence: 99%

“…A recent study by Palanques-Pastor et al [ 4 ] has characterized COVID-19 in adult patients with AML. They included four more frequent mutations in their study, among them, patients with a positive Flt3-ITD mutation seemed to be more prone to death by COVID-19.…”

mentioning

confidence: 99%

Flt3-ITD mutated acute myeloid leukemia patients and COVID-19: potential roles of autophagy and HIF-1α in leukemia progression and mortality

et al. 2022

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Characteristics, clinical outcomes, and risk factors of SARS-COV-2 infection in adult acute myeloid leukemia patients: experience of the PETHEMA group

Cited by 28 publications

References 35 publications

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9)

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

Flt3-ITD mutated acute myeloid leukemia patients and COVID-19: potential roles of autophagy and HIF-1α in leukemia progression and mortality

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