The challenge of COVID-19 for HSCT
Already early in the COVID-19 pandemic, the European Society for Blood and Marrow Transplantation set up a COVID-19 registry to collect data on overall survival, development of lower respiratory tract disease, need for intensive care unit administration and resolution of COVID-19. Overall survival in infected transplanted patients was found to be poor, with almost 25% of patients who underwent an allogeneic hematopoietic stem cell transplantation dying within the first six weeks after being diagnosed with COVID-19. Only age at COVID-19 diagnosis and performance status were found to be risk factors for poor survival.
Already at start of the COVID-19 pandemic, the European Society for Blood and Marrow Transplantation (EBMT) formulated recommendations for transplant centres on how to deal with COVID-19. These recommendations included prevention policies and procedures, guidance on how to deal with patients waiting for transplantation, donor considerations, recommendations with respect to visitors and family members, staff training, advice to patients after transplantation, etc. In addition to this, the EBMT, in collaboration with the Spanish Group of Transplant (GETH), initiated a registry data collection on February 28th. During his presentation at the annual EBMT meeting, Prof. Ljungman discussed the results of an analysed cohort of patients who have been diagnosed with COVID-19 before April 10th (N= 272) as well as a snapshot of the total registered cohort as of August 4th. For this larger cohort, only descriptive data are available thus far.1
The EBMT COVID-19 registry
The fully analysed cohort of the EBMT registry included 272 patients of whom 175 received an allogeneic haematopoietic stem cell transplantation (allo-HSCT) and 97 patients underwent an autologous HSCT (auto-HSCT) as their most recent transplantation. Most patients came from reporting countries Spain (N= 119), Italy (N= 44) and the United Kingdom (N= 29), but also thirteen Belgian patients were registered. The median time from transplant for the allo-HSCT patients was 13.7 months, as compared to 25.0 months for auto-HSCT patients. The median age of registered patients was 54.4 years and 60.9 years for allo-HSCT and auto-HSCT patients, respectively. The most common COVID-19 symptoms upon registration were fever, cough, fatigue and upper respiratory symptoms. In total, 43.4% of the patients in the allo-HSCT cohort and 50.8% of the patients in the auto-HSCT cohort required oxygen at diagnosis.1
The overall survival (OS) among HSCT patients with a COVID-19 infection was poor, both for patients receiving an allo-HSCT and an auto-HSCT, with six-week mortality rates of 23.2% and 16.2%, respectively (p= 0.23). The registry did reveal a trend for a better outcome in children (six-week OS of 94.4% vs. 74.9%, p= 0.12) compared to adults in the allo-HSCT cohort. Similar results were reported for the total cohort but only very few children underwent an auto-HSCT. Only age at COVID-19 diagnosis and performance status were found to be risk factors for poor survival (p= 0.01 and p= 0.0003, respectively) while time from transplant, ongoing immunosuppression, immuno-suppression index, diagnosis, type of HCT, lymphocyte count, neutrophil count, existing lung pathology or country did not seem to influence the survival outcomes.1
The results of the initial analysed cohort were confirmed in the total cohort of the EBMT COVID-19 registry (N= 398) without a significant difference in OS between patients who previously received an allo- or auto-HSCT (p= 0.15). In the total cohort, the OS difference between paediatric and adult patients almost reached statistical significance (p= 0.06). Preliminary outcome data indicate that 20.8% of the registered patients died because of COVID-19 while 4.0% died because of other causes. At the time of the analysis, 31.1% of the patients was alive and virus free, 10.3% was alive and clinically resolved and 10.8% was alive and still virus positive. From the other patients, no follow-up data were available.1
The impact of COVID-19 on HSCT patients was further exemplified by Prof. Orchard. In the United Kingdom, the total HSCT activity reported to the BSBMTCT registry in the time period of January 1th until June 30th 2020, dropped by 44% as compared to the same period in 2019. Furthermore, at last follow-up, 8 out of 34 (23.5%) UK allo-HSCT patients and 5 out of 16 (31.2%) of auto-HSCT infected patients died because of COVID-19.2
Conclusions
COVID-19, like other respiratory viruses, can have severe implications in HSCT recipients. Increased age and poor performance status are the most important risk factors for poor outcome. No obvious effect of time from HSCT could be observed, although there might be selection mechanisms influencing this result. Additional analyses are needed regarding possible interventions that mitigate the harmful effects of COVID-19. So far, measurements for preventing infections are highly recommended.
References
1. Ljungman P. The challenge of COVID-19 for HSCT: EBMT recommendations and prospective registry study. Presented at EBMT 2020; Session SS1-1.
2. Orchard K. The challenge of COVID-19 for HSCT in the UK. Presented at EBMT 2020; Session SS1-4.
