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COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)

COVID-19 is a severe infectious complication in patients with underlying medical conditions such as having undergone hematopoietic stem cell transplantation (HCT). This prospective survey reports outcome on 272 COVID-19 patients from 19 countries having undergone allogeneic (n = 175) or autologous (...

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Autores principales: Ljungman, Per, De La Camara, Rafael, Mikulska, Malgorzata, Tridello, Gloria, Aguado, Beatriz, Beguin, Yves, Martino Bufarull, Rodrigo, Ciceri, Fabio, Corral, Lucía López, Crippa, Claudia, Deeren, Dries, Duarte, Rafael F., Fox, María Laura, Grassi, Anna, Jimenez, María-José, Koculu, Safiye, Kwon, Mi, Vallejo Llamas, Juan Carlos, Lopez Lorenzo, Jose Luiz, Mielke, Stephan, López Jiménez, Javier, Mesa Morales, Zoraida, Orchard, Kim H., Parody Porras, Rocio, Potter, Victoria, Suárez-Lledó, María, Schaap, Nicolaas, Simand, Celestine, Sisinni, Luisa, Snowden, John A, Vallisa, Daniele, Yonalhindilerden, Ipek, Xhaard, Alienor, Knelange, Nina Simone, Cedillo, Angel, Kröger, Nicolaus, Piñana Sanchez, Jose Luis, Styczynski, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330149/
http://dx.doi.org/10.1182/blood-2020-138732
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author Ljungman, Per
De La Camara, Rafael
Mikulska, Malgorzata
Tridello, Gloria
Aguado, Beatriz
Beguin, Yves
Martino Bufarull, Rodrigo
Ciceri, Fabio
Corral, Lucía López
Crippa, Claudia
Deeren, Dries
Duarte, Rafael F.
Fox, María Laura
Grassi, Anna
Jimenez, María-José
Koculu, Safiye
Kwon, Mi
Vallejo Llamas, Juan Carlos
Lopez Lorenzo, Jose Luiz
Mielke, Stephan
López Jiménez, Javier
Mesa Morales, Zoraida
Orchard, Kim H.
Parody Porras, Rocio
Potter, Victoria
Suárez-Lledó, María
Schaap, Nicolaas
Simand, Celestine
Sisinni, Luisa
Snowden, John A
Vallisa, Daniele
Yonalhindilerden, Ipek
Xhaard, Alienor
Knelange, Nina Simone
Cedillo, Angel
Kröger, Nicolaus
Piñana Sanchez, Jose Luis
Styczynski, Jan
author_facet Ljungman, Per
De La Camara, Rafael
Mikulska, Malgorzata
Tridello, Gloria
Aguado, Beatriz
Beguin, Yves
Martino Bufarull, Rodrigo
Ciceri, Fabio
Corral, Lucía López
Crippa, Claudia
Deeren, Dries
Duarte, Rafael F.
Fox, María Laura
Grassi, Anna
Jimenez, María-José
Koculu, Safiye
Kwon, Mi
Vallejo Llamas, Juan Carlos
Lopez Lorenzo, Jose Luiz
Mielke, Stephan
López Jiménez, Javier
Mesa Morales, Zoraida
Orchard, Kim H.
Parody Porras, Rocio
Potter, Victoria
Suárez-Lledó, María
Schaap, Nicolaas
Simand, Celestine
Sisinni, Luisa
Snowden, John A
Vallisa, Daniele
Yonalhindilerden, Ipek
Xhaard, Alienor
Knelange, Nina Simone
Cedillo, Angel
Kröger, Nicolaus
Piñana Sanchez, Jose Luis
Styczynski, Jan
author_sort Ljungman, Per
collection PubMed
description COVID-19 is a severe infectious complication in patients with underlying medical conditions such as having undergone hematopoietic stem cell transplantation (HCT). This prospective survey reports outcome on 272 COVID-19 patients from 19 countries having undergone allogeneic (n = 175) or autologous (n = 97) HCT reported to the EBMT registry or to the GETH. All patients had the diagnosis of SARS-CoV-2 documented by PCR. Patients were included in this analysis if COVID-19 diagnosis was before April 10, 2020. The overall survival was estimate by using the Kaplan Meier methods, considering the death due to any cause as an event and the time from COVID-19 infection to the latest follow-up as survival time; difference between groups were tested by the log-rank test. Univariate and multivariate risk factor analysis for overall survival were performed with the Cox regression model. The median age was 54.4 years (1.0 - 80.3) for allogeneic and 60.9 years (7.7 - 73.4) for autologous HCT patients. 20 patients were children (< 18 years of age; median age 11.3 (1.0 - 16.9)). The median time from HCT to diagnosis of COVID-19 was 13.7 months (0.2 - 254.3) in allogeneic and 25.0 months (-0.9 - 350.3) in autologous recipients. Lower respiratory tract disease (LRTD) developed in 84.8% and 21.5% were admitted to an intensive care unit (ICU). At the time of analysis, 68/238 (28.6%) patients had died (47/155 allogeneic patients; 21/83 autologous patients). No follow-up had been received on 34 patients. The median time from infection to death was 19 days (0-102). Five patients were reported to have other primary causes of death than COVID-19. Of the patients reported to be alive, the median follow-up was 44 days. 144 (84.7%) patients (93 allogeneic; 51 autologous) had virologic resolution of the COVID-19 infection having at least one negative PCR. 26 patients were alive and known to be still COVID-19 positive (15 allogeneic; 11 autologous). For 34 patients the resolution status was unknown. Factors influencing the likelihood of resolution in multivariate analysis were underlying diagnosis (p=.01) and longer time from transplant to diagnosis of COVID-19 (p=.035). Overall survival at 6 weeks from COVID-19 diagnosis was 76.8% and 83.8% in allogeneic and autologous HCT recipients (p =ns), respectively (figure 1). Children (n=20) tended to do better with a 6-week survival of 95.0% although the difference was not significantly different (p =.12). In multivariate analysis of the total population older age (HR 1.26; 95% CI 1.05 - 1.51; p = .01) increased the risk and better performance status decreased the risk for fatal outcome (HR 0.79; 95% CI 0.69 - 0.90; p = .0003). The same factors had significant impact on overall survival in allogeneic HCT recipients (age HR 1.28; 95% CI 1.05 - 1.55; p=.01; performance status HR 0.79; 95% CI 0.68 - 0.92); p=.002) while only age impacted survival among autologous HCT patients (data not shown). Other transplant factors such as underlying diagnosis, time from HCT to diagnosis of COVID-19, graft-vs-host disease, or ongoing immunosuppression did not have a significant impact on overall survival. We conclude that HCT patients are at an increased risk compared to the general population to develop LRTD, require admission to ICU, and have increased mortality in COVID-19. [Figure: see text] DISCLOSURES: Duarte:Incyte Corporation: Other: Has received speaker and advisor fees. Kwon:Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Mielke:Novartis: Honoraria, Other: received via my institution, Speakers Bureau; Celgene/BMS: Honoraria, Other: received via my institution , Speakers Bureau; Bellicum: Honoraria, Other: received via my institution, Speakers Bureau; Kite/Gilead: Honoraria, Other: received via my institution , Speakers Bureau; Miltenyi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: received via my institution , Speakers Bureau; KIADIS Pharma: Honoraria, Other: received via my institution , Speakers Bureau; DNA Prime: Honoraria, Other: received via my institution , Speakers Bureau. López Jiménez:MSD: Speakers Bureau; Roche: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Abbvie: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau.
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spelling pubmed-83301492021-08-03 COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH) Ljungman, Per De La Camara, Rafael Mikulska, Malgorzata Tridello, Gloria Aguado, Beatriz Beguin, Yves Martino Bufarull, Rodrigo Ciceri, Fabio Corral, Lucía López Crippa, Claudia Deeren, Dries Duarte, Rafael F. Fox, María Laura Grassi, Anna Jimenez, María-José Koculu, Safiye Kwon, Mi Vallejo Llamas, Juan Carlos Lopez Lorenzo, Jose Luiz Mielke, Stephan López Jiménez, Javier Mesa Morales, Zoraida Orchard, Kim H. Parody Porras, Rocio Potter, Victoria Suárez-Lledó, María Schaap, Nicolaas Simand, Celestine Sisinni, Luisa Snowden, John A Vallisa, Daniele Yonalhindilerden, Ipek Xhaard, Alienor Knelange, Nina Simone Cedillo, Angel Kröger, Nicolaus Piñana Sanchez, Jose Luis Styczynski, Jan Blood 721.Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities COVID-19 is a severe infectious complication in patients with underlying medical conditions such as having undergone hematopoietic stem cell transplantation (HCT). This prospective survey reports outcome on 272 COVID-19 patients from 19 countries having undergone allogeneic (n = 175) or autologous (n = 97) HCT reported to the EBMT registry or to the GETH. All patients had the diagnosis of SARS-CoV-2 documented by PCR. Patients were included in this analysis if COVID-19 diagnosis was before April 10, 2020. The overall survival was estimate by using the Kaplan Meier methods, considering the death due to any cause as an event and the time from COVID-19 infection to the latest follow-up as survival time; difference between groups were tested by the log-rank test. Univariate and multivariate risk factor analysis for overall survival were performed with the Cox regression model. The median age was 54.4 years (1.0 - 80.3) for allogeneic and 60.9 years (7.7 - 73.4) for autologous HCT patients. 20 patients were children (< 18 years of age; median age 11.3 (1.0 - 16.9)). The median time from HCT to diagnosis of COVID-19 was 13.7 months (0.2 - 254.3) in allogeneic and 25.0 months (-0.9 - 350.3) in autologous recipients. Lower respiratory tract disease (LRTD) developed in 84.8% and 21.5% were admitted to an intensive care unit (ICU). At the time of analysis, 68/238 (28.6%) patients had died (47/155 allogeneic patients; 21/83 autologous patients). No follow-up had been received on 34 patients. The median time from infection to death was 19 days (0-102). Five patients were reported to have other primary causes of death than COVID-19. Of the patients reported to be alive, the median follow-up was 44 days. 144 (84.7%) patients (93 allogeneic; 51 autologous) had virologic resolution of the COVID-19 infection having at least one negative PCR. 26 patients were alive and known to be still COVID-19 positive (15 allogeneic; 11 autologous). For 34 patients the resolution status was unknown. Factors influencing the likelihood of resolution in multivariate analysis were underlying diagnosis (p=.01) and longer time from transplant to diagnosis of COVID-19 (p=.035). Overall survival at 6 weeks from COVID-19 diagnosis was 76.8% and 83.8% in allogeneic and autologous HCT recipients (p =ns), respectively (figure 1). Children (n=20) tended to do better with a 6-week survival of 95.0% although the difference was not significantly different (p =.12). In multivariate analysis of the total population older age (HR 1.26; 95% CI 1.05 - 1.51; p = .01) increased the risk and better performance status decreased the risk for fatal outcome (HR 0.79; 95% CI 0.69 - 0.90; p = .0003). The same factors had significant impact on overall survival in allogeneic HCT recipients (age HR 1.28; 95% CI 1.05 - 1.55; p=.01; performance status HR 0.79; 95% CI 0.68 - 0.92); p=.002) while only age impacted survival among autologous HCT patients (data not shown). Other transplant factors such as underlying diagnosis, time from HCT to diagnosis of COVID-19, graft-vs-host disease, or ongoing immunosuppression did not have a significant impact on overall survival. We conclude that HCT patients are at an increased risk compared to the general population to develop LRTD, require admission to ICU, and have increased mortality in COVID-19. [Figure: see text] DISCLOSURES: Duarte:Incyte Corporation: Other: Has received speaker and advisor fees. Kwon:Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Mielke:Novartis: Honoraria, Other: received via my institution, Speakers Bureau; Celgene/BMS: Honoraria, Other: received via my institution , Speakers Bureau; Bellicum: Honoraria, Other: received via my institution, Speakers Bureau; Kite/Gilead: Honoraria, Other: received via my institution , Speakers Bureau; Miltenyi: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: received via my institution , Speakers Bureau; KIADIS Pharma: Honoraria, Other: received via my institution , Speakers Bureau; DNA Prime: Honoraria, Other: received via my institution , Speakers Bureau. López Jiménez:MSD: Speakers Bureau; Roche: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Abbvie: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau. American Society of Hematology 2020-11-05 2021-08-03 /pmc/articles/PMC8330149/ http://dx.doi.org/10.1182/blood-2020-138732 Text en Copyright © 2020 American Society of Hematology. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle 721.Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities
Ljungman, Per
De La Camara, Rafael
Mikulska, Malgorzata
Tridello, Gloria
Aguado, Beatriz
Beguin, Yves
Martino Bufarull, Rodrigo
Ciceri, Fabio
Corral, Lucía López
Crippa, Claudia
Deeren, Dries
Duarte, Rafael F.
Fox, María Laura
Grassi, Anna
Jimenez, María-José
Koculu, Safiye
Kwon, Mi
Vallejo Llamas, Juan Carlos
Lopez Lorenzo, Jose Luiz
Mielke, Stephan
López Jiménez, Javier
Mesa Morales, Zoraida
Orchard, Kim H.
Parody Porras, Rocio
Potter, Victoria
Suárez-Lledó, María
Schaap, Nicolaas
Simand, Celestine
Sisinni, Luisa
Snowden, John A
Vallisa, Daniele
Yonalhindilerden, Ipek
Xhaard, Alienor
Knelange, Nina Simone
Cedillo, Angel
Kröger, Nicolaus
Piñana Sanchez, Jose Luis
Styczynski, Jan
COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
title COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
title_full COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
title_fullStr COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
title_full_unstemmed COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
title_short COVID-19 and Stem Cell Transplantation; Results from the Prospective Survey By the Infectious Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) and the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
title_sort covid-19 and stem cell transplantation; results from the prospective survey by the infectious diseases working party of the european society for blood and marrow transplantation (ebmt) and the spanish hematopoietic stem cell transplantation and cell therapy group (geth)
topic 721.Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330149/
http://dx.doi.org/10.1182/blood-2020-138732
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