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

Covid19 Clinical Trial

— AutoCOVID-19  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04760184
• Other study ID #: 2020-03433
• Status: Completed
• Start date: April 1, 2021
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2022
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 31, 2021
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Hematologic Neoplasms
• Lymphoma
• Malignant Lymphoma
• Multiple Myeloma
• Myeloma Multiple
• Neoplasms, Plasma Cell
• Stem Cell Transplant Complications

Intervention

Other:
• Autologous stem cell transplantation
The study will describe the implications of COVID-19 infection following autologous stem cell transplantation

Locations

Country	Name	City	State
Sweden	Uppsala Universitet	Uppsala

Sponsors (8)

Lead Sponsor	Collaborator
Uppsala University	Karolinska University Hospital, Lund University Hospital, Region Örebro County, Sahlgrenska University Hospital, Sweden, University Hospital, Linkoeping, University Hospital, Umeå, Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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;:. — View Citation

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. — View Citation

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, Kröger 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. Review. Erratum in: Bone Marrow Transplant. 2020 Jun 8;:. — View Citation

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. — View Citation

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. — View Citation

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, Bertù 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. — View Citation

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. — View Citation

Piñana JL, Martino R, García-García I, Parody R, Morales MD, Benzo G, Gómez-Catalan I, Coll R, De La Fuente I, Luna A, Merchán B, Chinea A, de Miguel D, Serrano A, Pérez C, Diaz C, Lopez JL, Saez AJ, Bailen R, Zudaire T, Martínez D, Jurado M, Calbacho M, Vázquez L, Garcia-Cadenas I, Fox L, Pimentel AI, Bautista G, Nieto A, Fernandez P, Vallejo JC, Solano C, Valero M, Espigado I, Saldaña R, Sisinni L, Ribera JM, Jimenez MJ, Trabazo M, Gonzalez-Vicent M, Fernández 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. — View Citation

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. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	Overall survival after infection with COVID-19	30 days
Primary	Overall survival	Overall survival after infection with COVID-19	90 days
Primary	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	Time of COVID-19 infection	Time of SARS-CoV-2 infection in relation to autologous stem cell transplantation	Up to 15 months
Secondary	Hospitalization	Duration of hospitalization	Up to 15 months
Secondary	Oxygen treatment	Duration of oxygen treatment	Up to 15 months
Secondary	High-flow oxygen therapy	Duration of high-flow oxygen therapy	Up to 15 months
Secondary	Non-invasive ventilation	Duration of non-invasive ventilation (NIV)	Up to 15 months
Secondary	Intensive care	Duration of care in intensive care unit	Up to 15 months
Secondary	Invasive mechanical ventilation	Duration of Invasive mechanical ventilation	Up to 15 months
Secondary	ECMO	Duration of extracorporeal membrane oxygenation (ECMO)	Up to 15 months
Secondary	Occurence of ARDS	Diagnosis of Acute respiratory distress syndrome (ARDS)	Up to 15 months
Secondary	Occurence of arterial thrombosis	Event of arterial thrombosis	Up to 15 months
Secondary	Occurence of venous thrombosis	Event of venous thrombosis	Up to 15 months
Secondary	Occurence of arrhythmias	Event of recorded arrhythmias	Up to 15 months
Secondary	Occurence of acute cardiac injury	Event of acute cardiac injury	Up to 15 months
Secondary	Occurence of secondary infection	Event of any secondary infection	Up to 15 months
Secondary	Occurence of cytokine release syndrome	Event of cytokine release syndrome	Up to 15 months
Secondary	Comorbidities	Description of comorbidities prior to autologous stem cell transplantation	Prior to autologous stem cell transplantation
Secondary	Disease status	Description of disease status prior to autologous stem cell transplantation	Prior to autologous stem cell transplantation
Secondary	Previous disease modifying treatment	Description of previous disease modifying treatment prior to autologous stem cell transplantation	Prior to autologous stem cell transplantation
Secondary	Conditioning treatment	Description of conditioning treatment prior to autologous stem cell transplantation	At autologous stem cell transplantation
Secondary	Time of infection	Time of COVID-19 in relation to autologous stem cell transplantation	At autologous stem cell transplantation or up to 15 months
Secondary	Neutropenia	Event of neutropenia at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated CRP	Event of elevated C-reactive protein (CRP) at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated leukocyte count	Event of elevated leukocyte count at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Lymphocytopenia	Event of lymphocytopenia at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated liver enzymes	Event of elevated liver enzymes at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated lactate dehydrogenase	Event of elevated lactate dehydrogenase at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated ferritin	Event of elevated ferritin at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated d-dimer	Event of elevated d-dimer at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	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
Secondary	Elevated troponin	Event of elevated troponin at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months
Secondary	Elevated creatinine	Event of elevated creatinine at diagnosis of COVID-19	At autologous stem cell transplantation or up to 15 months