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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Covid19, Myeloma Multiple, Malignant Lymphoma, Hematologic Neoplasms, Stem Cell Transplant Complications

Intervention / Treatment
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* Other: Autologous stem cell transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID19 positives after autologous stem cell transplantation<br>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<br>* The study will describe the implications of COVID-19 infection following autologous stem cell transplantation<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous stem cell transplantation, COVID-19