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1.
Marchesi, Francesco, Salmanton-Garcia, Jon, Emarah, Ziad, Piukovics, Klára, Nucci, Marcio, Lopez-Garcia, Alberto, Racil, Zdenek, Farina, Francesca, Popova, Marina, Zompi, Sofia, Audisio, Ernesta, Ledoux, Marie-Pierre, Verga, Luisa, Weinbergerova, Barbora, Szotkowski, Tomas, Silva, Maria, Fracchiolla, Nicola Stefano, De Jonge, Nick, Collins, Graham, Marchetti, Monia, Magliano, Gabriele, GarcÍA-Vidal, Carolina, Biernat, Monika, Doesum, Jaap van, Machado, Marina, Demirkan, Fatih, Khabori, Murtadha Al, Zak, Pavel, Visek, Benjamin, Stoma, Igor, MÉNdez, Gustavo-Adolfo, Maertens, Johan, Khanna, Nina, Espigado, Ildefonso, Dragonetti, Giulia, Fianchi, Luana, Principe, Maria Ilaria Del, Cabirta, Alba, Ormazabal-VÉLez, Irati, Jaksic, Ozren, Buquicchio, Caterina, Bonuomo, Valentina, Batinić, Josip, Omrani, Ali, Lamure, Sylvain, Finizio, Olimpia, FernÁNdez, Noemí, Falces-Romero, Iker, Blennow, Ola, Bergantim, Rui, Ali, Natasha, Win, Sein, Praet, Jens V. A. N.; Tisi, Maria Chiara, Shirinova, Ayten, SchÖNlein, Martin, Prattes, Juergen, Piedimonte, Monica, Petzer, Verena, NavrÁTil, Milan, Kulasekararaj, Austin, Jindra, Pavel, Jiří, Glenthøj, Andreas, Fazzi, Rita, de Ramón, Cristina, Cattaneo, Chiara, Calbacho, Maria, Bahr, Nathan, El-Ashwl, Shaimaa Saber, Córdoba, Raúl, Hanakova, Michaela, Zambrotta, Giovanni, Sciumè, Mariarita, Booth, Stephen, Nunes-Rodrigues, Raquel, Sacchi, Maria Vittoria, GarcÍA-PoutÓN, Nicole, MartÍN-GonzÁLez, Juan-Alberto, Khostelidi, Sofya, GrÄFe, Stefanie, Rahimli, Laman, busca, alessandro, Corradini, Paolo, Hoenigl, Martin, Klimko, Nikolai, Koehler, Philipp, Pagliuca, Antonio, Passamonti, Francesco, Cornely, Oliver, pagano, Livio.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328805

ABSTRACT

Patients with acute myeloid leukemia (AML) are at high risk of mortality from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients with COVID-19 diagnosis between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the prior 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died. Death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%). Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with an improved survival when AML treatment could be delayed. Patients with COVID-19 diagnosis between January and August 2020 had a significantly lower survival. COVID-19 in AML patients was associated with a high mortality rate and modifications of therapeutic algorithms. The best approach to improve survival was to delay AML treatment.

3.
Blood ; 136(Supplement 1):12-13, 2020.
Article in English | PMC | ID: covidwho-1338992

ABSTRACT

Peter Paschka and Hartmut Döhner contributed equally.Background. SARS-CoV-2 infection (COVID-19) has had a great impact worldwide and its mortality has been reported to be higher in patients with haematological malignancies. However, description of its effects and outcomes among recipient of hematopoietic stem cell transplantation (HSCT) is scarce.Objectives. To describe the characteristics, treatment and outcome of COVID-19 in recipients of HSCT reported to the Madrid registry of COVID-19 ("HEMATO-MADRID COVID-19 registry").Results. Data of 842 patients from 23 hospitals with haematological malignancies and COVID-19 infection were reported in the Madrid registry between March and June 2020. Among those, 87 (10.3%) patients were HSCT recipients: 58 auto-HSCT and 29 allo-HSCT (7 of them from matched related donor (MRD), 12 matched unrelated donor (MUD) and 10 haplo-HSCT). Characteristics of the population are described in Table 1. Median age at COVID-19 infection was 61 years (IQR, 53-67) and 35 patients (40%) were female. Recipients of auto-HSCT with COVID-19 were older and showed a trend towards a higher incidence of arterial hypertension (28% vs 10%, p=0.067) without statistical differences in other comorbidities;active disease requiring treatment at COVID-19 diagnosis was more frequent in auto-HSCT recipients (65% vs. 21%, p<0.001). Median time from transplant to COVID19 infection was shorter in allo-HSCT patients (32 vs. 19 months, p=0.043). Nearly 40% of allo-recipients had active GVHD at COVID-19 debut, including pulmonary GVHD. A total of 63 (72%) patients required hospital admission and 13 patients (15%) received intensive care support. Allo-recipients showed a trend towards a higher need of hospital admission (79% vs. 68%, p=0.081). Most patients received anti-viral treatment with either hydroxichloroquine (47 patients, 54%), lopinavir/ritonavir (34 patients, 39%), remdesivir (5, 4%) and/or other treatments including azythromicin or interferon. 23 patients (26%) received anticytokine treatment with tocilizumab (15, 17%) and/or anakinra (8, 9%) and 27 patients (31%) received steroids. The overall response rate to treatment and supportive care was 80% in both groups. After a median follow-up of 50 days after the infection debut, overall-survival at day 50 was 84% for auto and 82% for allo-HSCT recipients (p=0.915). However, global mortality rate among the complete observation period was significantly higher in allo-recipients (24% vs. 17%, p <0.001).Conclusion. In our multicentric experience in a high COVID-19 impacted area, the median time of COVID-19 infection presentation was relatively late in transplanted patients, however shorter in allo-transplanted patients. COVID-19 related mortality was high in HSCT recipients, significantly higher in allo-transplanted patients. Factors associated to this higher mortality should be further investigated to promptly identify high-risk patients since the pandemic is still highly active worldwide.

4.
Blood ; 136(Supplement 1):19-19, 2020.
Article in English | PMC | ID: covidwho-1338945

ABSTRACT

Introduction and objective. SARS-CoV-2 pandemic has deeply impacted in Spain. In cancer patients (pts) the lethality has been higher than in normal population, but, little is known on the impact in adults with ALL. Our objective was to analyze the frequency, clinical characteristics and outcome of adult ALL patients infected by SARS-CoV-2.Methods. Between March 1, 2020 and May 31, 2020 (the period of the peak of COVID-19 infection in Spain) two registries from the PETHEMA (Programa Español de Tratamientos en Hematologia) and GETH (Grupo Español de Trasplante Hematopoyético y Terapia Celular) groups were activated to recruit adult patients with ALL and COVID-19 infection confirmed by PCR. The PETHEMA registry was based on ASH proposal (www.ashresearchcollaborative.org/covid-19-registry) and the GETH registry was specifically performed for hematological diseases and COVID-19 infection. Both registries were merged for this study. Eighty-four Spanish centers were contacted and weekly reminds were sent until May 19, 2020. The demographic and clinical characteristics of ALL and COVID-19 infection, the comorbidities, the treatment and outcome were collected. The study was closed for follow in July 10, 2020.Results. Fifty-six of 84 centers answered the survey and 28 patients with ALL and COVID-19 infection were identified in 17 of them, especially on March (n=11) and April (n=15). Median age was 46 (range 20-78) yrs. and 19 were aged over 40 yrs. Fifteen pts were male, 1 was active smoker and 9 showed one or more comorbidities (chronic liver disease [n=2] diabetes [n=1], hypertension [n=5], cardiopathy [n=2], prior malignancy [n=1] and hypogammaglobulinemia [n=1]). ALL was of B-cell precursors in 18 pts (Ph+ in 6) and T in 10. Twenty-six pts were on treatment of LAL (induction [n=10], consolidation [n=3], maintenance [n=1], HSCT [n=5], rescue [n=6], and palliative [n=1]). Eight patients were previously submitted to allogeneic HSCT, CAR T [n=1] or immunotherapy with monoclonal antibodies (inotuzumab, n=4) and 21 were receiving immunosuppressive drugs (corticosteroids in 11, fludarabine in 4, among others). Eleven pts showed neutropenia <0.5x109/L and 18 lymphocytopenia <0.5x109/L. Median value of C reactive protein was 28.7 mg/L (0.9-311.7) and D-dimer 690 ng/mL (120-31,200). The main clinical characteristics of COVID-19 infection were: fever (n=18), cough (n=16), shortness of breath (n=9) and asthenia (n=11) and 5 pts were asymptomatic. The most frequency therapies were hydroxychloroquine/chloroquine (n=23), combined or not with lopinavir/ritonavir. Tocilizumab was given to 8 pts. Twelve pts required oxygen supply and 7 required ICU support (median stay 16 [1-47] days). COVID-19 was solved in 18 pts, although 5 pts showed PCR+ persistence (median 25 [16-91] days) after resolution of symptoms. The treatment of ALL was stopped/modified in 11 pts. Nine pts dead (COVID-19 [n=6], COVID-19 and ALL progression [n=2] and COVID-19 andPseudomonassepsis [n=1]). A trend for higher mortality was observed in patients with neutropenia <0.5x109/L and in those with lymphocytopenia <0.5x109/L.Conclusion. The frequency of adult patients with ALL and COVID-19 infection can be considered high, given the low incidence of adult ALL. COVID-19 infection was frequent in patients with advanced age and on ALL therapy. The frequency of severe COVID-19 infection and the mortality were high.Supported in part by 2017 SGR288 (GRC) Generalitat de Catalunya and "la Caixa" Foundation.

5.
Clin Lymphoma Myeloma Leuk ; 21(10): e801-e809, 2021 10.
Article in English | MEDLINE | ID: covidwho-1313013

ABSTRACT

BACKGROUND AND OBJECTIVE: SARS-CoV-2 infection has bimodal distribution in Europe with a first wave in March to June 2020 and a second in September 2020 to February 2021. We compared the frequency, clinical characteristics and outcomes of adults with acute lymphoblastic leukemia (ALL) and infection in the first vs. second pandemic waves in Spain. PATIENTS AND METHODS: In this prospective study the characteristics of ALL and COVID-19 infection, comorbidities, treatment and outcome in the two periods were compared. The study ended when vaccination against SARS-CoV-2 was implemented in Spain. RESULTS: Twenty eight patients were collected in the first wave and 24 in the second. The median age was 46.5 years (range 20-83). Patients from the first wave had a trend to more severe ALL (higher frequency of patients under induction or submitted to transplantation or under immunosuppressive therapy). No significant differences were observed in need for oxygen support, intensive care unit (ICU) requirement, days in ICU and time to COVID-19 infection recovery. Seventeen patients (33%) died, with death attributed to COVID infection in 15 (29%), without significant differences in the 100 day overall survival (OS) probabilities in the two waves (68% ± 17% vs. 56% ± 30%). The only prognostic factor for OS identified by was the presence of comorbidities at COVID-19 infection (HR: 5.358 [95% CI: 1.875- 15.313]). CONCLUSION: The frequency and mortality of COVID-19 infection were high in adults with ALL, without changes over time, providing evidence in favor of vaccination priority for these patients.


Subject(s)
COVID-19/epidemiology , Intensive Care Units/statistics & numerical data , Outcome Assessment, Health Care/statistics & numerical data , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19/therapy , COVID-19/virology , Comorbidity , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Outcome Assessment, Health Care/methods , Pandemics/prevention & control , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prospective Studies , SARS-CoV-2/physiology , Spain/epidemiology , Young Adult
6.
Leukemia ; 35(10): 2885-2894, 2021 10.
Article in English | MEDLINE | ID: covidwho-1253922

ABSTRACT

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19.


Subject(s)
COVID-19/complications , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/virology , Child , Child, Preschool , Female , Follow-Up Studies , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/virology , Humans , Infant , Male , Middle Aged , Prognosis , Prospective Studies , Survival Rate , Transplantation, Homologous , Young Adult
8.
Exp Hematol Oncol ; 9: 21, 2020.
Article in English | MEDLINE | ID: covidwho-730498

ABSTRACT

BACKGROUND: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). CONCLUSIONS: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.

9.
Eur J Haematol ; 105(5): 597-607, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-671499

ABSTRACT

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) in haematological patients (HP) has not been comprehensively reported. METHODS: We analysed 39 patients with SARS-CoV-2 infection and haematological malignancies. Clinical characteristics and outcomes were compared to a matched control group of 53 non-cancer patients with COVID-19. Univariate and multivariate analyses were carried out to assess the risk factors associated with poor outcome. RESULTS: The most frequent haematological diseases were lymphoma (30%) and multiple myeloma (30%). Eighty-seven % HP developed moderate or severe disease. Patients with haematological malignancies had a significantly higher mortality rate compared to non-cancer patients (35.9% vs 13.2%; P = .003 (odds ratio 6.652). The worst outcome was observed in chronic lymphocytic leukaemia patients. Only age >70 years and C reactive protein >10 mg/dl at admission were associated with higher risk of death (odds ratio 34.86, P = .003 and 13.56,P = .03). Persistent viral sheddind was detected in 5 HP. Active chemotherapy, viral load at diagnosis and COVID-19 therapy were not predictors of outcome. CONCLUSION: Mortality of COVID-19 is significantly higher in patients with haematological malignancies compared to non-cancer patients. The impact of persistent viral shedding must be considered in order to re-start therapies and maintain infectious control measures.


Subject(s)
COVID-19/complications , COVID-19/mortality , Hematologic Neoplasms/complications , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/blood , Case-Control Studies , Female , Hematologic Neoplasms/blood , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Lymphoma/complications , Male , Middle Aged , Multiple Myeloma/complications , Multivariate Analysis , Pandemics , Risk Factors , SARS-CoV-2 , Spain/epidemiology
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