Impact of COVID-19 After Autologous Hematopoietic Stem Cell Transplantation in Sweden (AutoCOVID-19)

Impact of COVID-19 on Patients Treated With Autologous Hematopoietic Stem Cell Transplantation in Sweden - a Retrospective Cohort Study

This retrospective observational cohort study aims to describe the impact of COVID-19 in patients treated with autologous stem cell transplantation (ASCT) for malignant disease in terms of risk factors, morbidity, need for supportive care and mortality. All patients treated with ASCT in Sweden from 1st January 2020 until 31st December 2020 are eligible for this study. Patients who also has tested positive for SARS-CoV-2 from start of conditioning or later will be identified through the national registry of the Public Health Agency of Sweden and a systematic analysis of their medical records will be performed.

Study Overview

• Status: Completed
• Conditions: Covid19; Hematologic Neoplasms; Stem Cell Transplant Complications; Myeloma Multiple; Malignant Lymphoma
• Intervention / Treatment: Other: Autologous stem cell transplantation

Detailed Description

Research question How does infection with SARS-CoV-2 affect patients with hematological malignancies who are treated with autologous hematopoietic stem cell transplantation?

Study population All Swedish citizens treated with ASCT for malignant disease in Sweden from 1st January 2020 until 31st December 2020 are eligible for this study. There will be a minimum follow-up time of one month for all patients.

Data collection and storage Patients will be identified using local ASCT registers at the seven university hospitals, as there is no national register for ASCT-patients in Sweden. These seven university hospitals are the only sights to perform ASCT in Sweden. The Public Health Agency of Sweden (Folkhälsomyndigheten - FHM) has the national responsibility to surveil and control communicable disease. The FHM uses several different surveillance systems to monitor the spread of COVID-19. Since COVID-19 is subject to mandatory reporting under the Communicable Diseases Act, physicians and laboratories continuously supply data to be analyzed daily by the FHM. The coverage of this database is estimated to be very high, close to 100%. For this study the investigators will link the patients identified through the ASCT-centers with the register of SARS-Cov-2 positive patients (SmiNet) held by the FHM. Patients who has tested positive for SARS-CoV-2 on the day of start of conditioning or at any given time thereafter will be included in the study. Inclusion of positive SARS-CoV-2 tests will start from 1st January 2020 until 31st March 2021 to allow for 3 months of follow-up after transplantation. For every ASCT-patient that has tested positive for COVID-19 after ASCT a systematic analysis of their medical records will be performed to describe the circumstances, impact and outcome of the COVID-19.

All data collected will be stored in a deidentified data set on a secure server held by Dalarna Country Council where name and social security number have been erased and given a coded study number. Each patient will only be identified using a separately stored code key. All storage, correspondence and analysis with the code key and pseudonymized data set will adhere to current European General Data Protection Regulation (GDPR) guidelines. The code key will be destroyed as soon as data collection is completed, data quality is secured and the final report is published. The data set will be stored for 10 years and then be destroyed.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • Uppsala Universitet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All Swedish citizens treated with ASCT for malignant disease in Sweden from 1st January 2020 until 31st December 2020 are eligible for this study. There will be a minimum follow-up time of one month for all patients.

Description

Inclusion Criteria:

• Diagnosis of hematological cancer (C81-C96 according to the International Classification of Diseases 10th revision (ICD-10).
• Autologous hematopoietic stem cell transplantation performed 1 January 2020 until 31st December 2020 at a Swedish transplantation center.
• Positive RT-PCR test for SARS-CoV-2 performed in Sweden

Exclusion Criteria:

- Age below 18 years and 0 months at the time of transplantation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID19 positives after autologous stem cell transplantation; All Swedish citizens treated with ASCT for malignant disease in Sweden from 1st January 2020 until 31st December 2020 who has tested positive for SARS-CoV-2 from start of conditioning until the end of the study period 31st March 2021.	Other: Autologous stem cell transplantation; The study will describe the implications of COVID-19 infection following autologous stem cell transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival after infection with COVID-19	30 days
Overall survival	Overall survival after infection with COVID-19	90 days
COVID-19 related mortality	As classified by the WHO; a death resulting from a clinically compatible illness in a confirmed COVID-19 case, unless there is a clear alternative cause of death that cannot be related to COVID disease (e.g., trauma). There should be no period of complete recovery between the illness and death	within 6 months after infection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of COVID-19 infection	Time of SARS-CoV-2 infection in relation to autologous stem cell transplantation	Up to 15 months
Hospitalization	Duration of hospitalization	Up to 15 months
Oxygen treatment	Duration of oxygen treatment	Up to 15 months
High-flow oxygen therapy	Duration of high-flow oxygen therapy	Up to 15 months
Non-invasive ventilation	Duration of non-invasive ventilation (NIV)	Up to 15 months
Intensive care	Duration of care in intensive care unit	Up to 15 months
Invasive mechanical ventilation	Duration of Invasive mechanical ventilation	Up to 15 months
ECMO	Duration of extracorporeal membrane oxygenation (ECMO)	Up to 15 months
Occurence of ARDS	Diagnosis of Acute respiratory distress syndrome (ARDS)	Up to 15 months
Occurence of arterial thrombosis	Event of arterial thrombosis	Up to 15 months
Occurence of venous thrombosis	Event of venous thrombosis	Up to 15 months
Occurence of arrhythmias	Event of recorded arrhythmias	Up to 15 months
Occurence of acute cardiac injury	Event of acute cardiac injury	Up to 15 months
Occurence of secondary infection	Event of any secondary infection	Up to 15 months
Occurence of cytokine release syndrome	Event of cytokine release syndrome	Up to 15 months
Comorbidities	Description of comorbidities prior to autologous stem cell transplantation	Prior to autologous stem cell transplantation
Disease status	Description of disease status prior to autologous stem cell transplantation	Prior to autologous stem cell transplantation
Previous disease modifying treatment	Description of previous disease modifying treatment prior to autologous stem cell transplantation	Prior to autologous stem cell transplantation
Conditioning treatment	Description of conditioning treatment prior to autologous stem cell transplantation	At autologous stem cell transplantation
Time of infection	Time of COVID-19 in relation to autologous stem cell transplantation	At autologous stem cell transplantation or up to 15 months
Neutropenia	Event of neutropenia at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated CRP	Event of elevated C-reactive protein (CRP) at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated leukocyte count	Event of elevated leukocyte count at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Lymphocytopenia	Event of lymphocytopenia at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated liver enzymes	Event of elevated liver enzymes at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated lactate dehydrogenase	Event of elevated lactate dehydrogenase at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated ferritin	Event of elevated ferritin at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated d-dimer	Event of elevated d-dimer at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Prolonged aPTT	Event of prolonged activated partial thromboplastin time (aPTT) at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated troponin	Event of elevated troponin at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Elevated creatinine	Event of elevated creatinine at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Karolinska University Hospital; Sahlgrenska University Hospital, Sweden; University Hospital, Linkoeping; Lund University Hospital; University Hospital, Umeå; Region Örebro County; Uppsala University Hospital
• Investigators: Principal Investigator: Honar Cherif, MD, Ass prof, Department of Medical Sciences, Uppsala University; Study Chair: Thomas Silfverberg, MD, Center for Clinical Research Dalarna and Department of Medical Sciences-Uppsala University; Study Chair: Kristina Carlson, MD, Ass Prof, Department of Medical Sciences, Uppsala University

Publications and helpful links

General Publications

• Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020 Feb 15;395(10223):497-506. doi: 10.1016/S0140-6736(20)30183-5. Epub 2020 Jan 24. Erratum In: Lancet. 2020 Jan 30;:
• Dai M, Liu D, Liu M, Zhou F, Li G, Chen Z, Zhang Z, You H, Wu M, Zheng Q, Xiong Y, Xiong H, Wang C, Chen C, Xiong F, Zhang Y, Peng Y, Ge S, Zhen B, Yu T, Wang L, Wang H, Liu Y, Chen Y, Mei J, Gao X, Li Z, Gan L, He C, Li Z, Shi Y, Qi Y, Yang J, Tenen DG, Chai L, Mucci LA, Santillana M, Cai H. Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak. Cancer Discov. 2020 Jun;10(6):783-791. doi: 10.1158/2159-8290.CD-20-0422. Epub 2020 Apr 28.
• Passamonti F, Cattaneo C, Arcaini L, Bruna R, Cavo M, Merli F, Angelucci E, Krampera M, Cairoli R, Della Porta MG, Fracchiolla N, Ladetto M, Gambacorti Passerini C, Salvini M, Marchetti M, Lemoli R, Molteni A, Busca A, Cuneo A, Romano A, Giuliani N, Galimberti S, Corso A, Morotti A, Falini B, Billio A, Gherlinzoni F, Visani G, Tisi MC, Tafuri A, Tosi P, Lanza F, Massaia M, Turrini M, Ferrara F, Gurrieri C, Vallisa D, Martelli M, Derenzini E, Guarini A, Conconi A, Cuccaro A, Cudillo L, Russo D, Ciambelli F, Scattolin AM, Luppi M, Selleri C, Ortu La Barbera E, Ferrandina C, Di Renzo N, Olivieri A, Bocchia M, Gentile M, Marchesi F, Musto P, Federici AB, Candoni A, Venditti A, Fava C, Pinto A, Galieni P, Rigacci L, Armiento D, Pane F, Oberti M, Zappasodi P, Visco C, Franchi M, Grossi PA, Bertu L, Corrao G, Pagano L, Corradini P; ITA-HEMA-COV Investigators. Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study. Lancet Haematol. 2020 Oct;7(10):e737-e745. doi: 10.1016/S2352-3026(20)30251-9. Epub 2020 Aug 13.
• Phelan AL, Katz R, Gostin LO. The Novel Coronavirus Originating in Wuhan, China: Challenges for Global Health Governance. JAMA. 2020 Feb 25;323(8):709-710. doi: 10.1001/jama.2020.1097. No abstract available.
• Mossad SB, Longworth DL, Goormastic M, Serkey JM, Keys TF, Bolwell BJ. Early infectious complications in autologous bone marrow transplantation: a review of 219 patients. Bone Marrow Transplant. 1996 Aug;18(2):265-71.
• Ljungman P, Ward KN, Crooks BN, Parker A, Martino R, Shaw PJ, Brinch L, Brune M, De La Camara R, Dekker A, Pauksen K, Russell N, Schwarer AP, Cordonnier C. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2001 Sep;28(5):479-84. doi: 10.1038/sj.bmt.1703139.
• Hutspardol S, Essa M, Richardson S, Schechter T, Ali M, Krueger J, Fujii H, Egeler RM, Gassas A. Significant Transplantation-Related Mortality from Respiratory Virus Infections within the First One Hundred Days in Children after Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2015 Oct;21(10):1802-7. doi: 10.1016/j.bbmt.2015.06.015. Epub 2015 Jun 25.
• Eichenberger EM, Soave R, Zappetti D, Small CB, Shore T, van Besien K, Douglass C, Westblade LF, Satlin MJ. Incidence, significance, and persistence of human coronavirus infection in hematopoietic stem cell transplant recipients. Bone Marrow Transplant. 2019 Jul;54(7):1058-1066. doi: 10.1038/s41409-018-0386-z. Epub 2018 Nov 1.
• He W, Chen L, Chen L, Yuan G, Fang Y, Chen W, Wu D, Liang B, Lu X, Ma Y, Li L, Wang H, Chen Z, Li Q, Gale RP. COVID-19 in persons with haematological cancers. Leukemia. 2020 Jun;34(6):1637-1645. doi: 10.1038/s41375-020-0836-7. Epub 2020 Apr 24.
• Ljungman P, Mikulska M, de la Camara R, Basak GW, Chabannon C, Corbacioglu S, Duarte R, Dolstra H, Lankester AC, Mohty M, Montoto S, Murray J, Peffault de Latour R, Snowden JA, Yakoub-Agha I, Verhoeven B, Kroger N, Styczynski J; European Society for Blood and Marrow Transplantation. The challenge of COVID-19 and hematopoietic cell transplantation; EBMT recommendations for management of hematopoietic cell transplant recipients, their donors, and patients undergoing CAR T-cell therapy. Bone Marrow Transplant. 2020 Nov;55(11):2071-2076. doi: 10.1038/s41409-020-0919-0. Epub 2020 May 13. Erratum In: Bone Marrow Transplant. 2020 Jun 8;:
• Terpos E, Engelhardt M, Cook G, Gay F, Mateos MV, Ntanasis-Stathopoulos I, van de Donk NWCJ, Avet-Loiseau H, Hajek R, Vangsted AJ, Ludwig H, Zweegman S, Moreau P, Einsele H, Boccadoro M, San Miguel J, Dimopoulos MA, Sonneveld P. Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN). Leukemia. 2020 Aug;34(8):2000-2011. doi: 10.1038/s41375-020-0876-z. Epub 2020 May 22.
• Pinana JL, Martino R, Garcia-Garcia I, Parody R, Morales MD, Benzo G, Gomez-Catalan I, Coll R, De La Fuente I, Luna A, Merchan B, Chinea A, de Miguel D, Serrano A, Perez C, Diaz C, Lopez JL, Saez AJ, Bailen R, Zudaire T, Martinez D, Jurado M, Calbacho M, Vazquez L, Garcia-Cadenas I, Fox L, Pimentel AI, Bautista G, Nieto A, Fernandez P, Vallejo JC, Solano C, Valero M, Espigado I, Saldana R, Sisinni L, Ribera JM, Jimenez MJ, Trabazo M, Gonzalez-Vicent M, Fernandez N, Talarn C, Montoya MC, Cedillo A, Sureda A; Infectious Complications Subcommittee of the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH). Risk factors and outcome of COVID-19 in patients with hematological malignancies. Exp Hematol Oncol. 2020 Aug 25;9:21. doi: 10.1186/s40164-020-00177-z. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Autologous stem cell transplantation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; COVID-19; Hematologic Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 2020-03433

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Upon request the pseudonymized data sheet will be made available for other researchers depending on purpose of the request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No