CHRONOS19: INTERIM ANALYSIS OF THE OBSERVATIONAL STUDY OF COVID-19 IN PATIENTS WITH BLOOD DISEASES
The emergence of a new infectious disease COVID-19 led to the extensive research of not only the coronavirus itself, but also the course of this disease in different patient populations. This is especially true for patients with a high risk of severe disease and mortality, in particular, those suffering from oncologic and hematologic diseases. In order to understand how COVID-19 develops in patients with hematologic (blood) diseases, a multicenter study CHRONOS19 was launched in June 2020 among patients with COVID-19 and hematologic diseases in Russia. The study was initiated by the National Research Center for Hematology in collaboration with regional hematology clinics; it was supported by the RakFond. The objectives of this study were to assess the mortality of these patients from both COVID-19 and the underlying disease, to identify risk factors associated with a higher risk of death, and to assess the likelihood of poor outcomes of the hematologic disease after COVID-19.
The CHRONOS19 registry is an observational study that unites 14 centers from 11 regions throughout Russia. Between June 22 and November 14, 2020, 379 patients were enrolled in the study, 335 of them were included in statistical analysis, a subject to data completeness that allowed to assess the primary endpoint, 30-day all-cause mortality. Longer-term results were evaluated only in those patients who reached 90 or 180 days of follow-up. Data collection is ongoing on the platform of RakFond’s partner, Enrollme.ru. Interim results of the study were presented at the last annual meeting of the American Society of Hematology (ASH) on December 5-8, 2020. The abstract received a special award from ASH, and it can be accessed here. A summary of the presentation is given below.
According to the registry, a vast majority of patients had malignant hematologic diseases (acute and chronic leukemias, lymphomas, multiple myeloma), and only 10% had the non-oncological hematologic disease. Only 12 patients underwent bone marrow transplantation during twelve months prior to the COVID-19, so this factor was excluded from further analysis. Every fifth patient (21%) had myelotoxic agranulocytosis – MTA (a pronounced decrease of leukocytes in the blood count after chemotherapy) at the time of COVID-19 diagnosis, over a third of patients (37%) were dependent on blood transfusions. Concomitant diseases were reported in more than half of the patients (61%).
At the time of data cut-off, the 30-day mortality rate was 22.3%. About a quarter of the patients (27%) were transferred to the intensive care unit (ICU) and required mechanical ventilation (23%). Among 74% of patients with complications of COVID-19, the most common were pneumonia (96%), and severe conditions such as cytokine release syndrome – CRS (10%) and acute respiratory distress syndrome – ARDS (10%). According to the statistical analysis, CRS was not associated with a leukocyte count of more than 1×109 / L and was reported at the same frequency rate in patients with MTA.
Admission to the ICU, mechanical ventilation, treatment phase of the hematologic disease (induction and relapsed or refractory disease), malignant disease, the severity of COVID-19, concomitant diseases (diabetes mellitus, cardiovascular diseases, respiratory diseases), dependence on blood transfusions, severe ECOG performance status, severe complications (ARDS, CRS) and the older age (over 60 years) were associated with a significantly higher risk of death. Furthermore, almost all patients who required mechanical ventilation and were admitted to the ICU due to the severity of the condition died (30-day overall survival rate was 4% and 11%, respectively). Among the causes of early mortality (within the first 30 days after the diagnosis of COVID-19), COVID-19 complications prevailed, while more deaths due to the progression of the hematologic disease were recorded at later follow-ups. The rates of disease progression and relapse after 30 and 90 days were comparable to the general population of patients with hematologic diseases.
In conclusion, all-cause mortality in patients with the hematologic disease is one order of magnitude higher than in the general population with COVID-19 (22% vs. approximately 2%). Further follow-up will reveal more insights into late-term outcomes and the significance of the COVID-19 pandemic for the treatment of patients with hematologic diseases and help determine the tactics of medical care for this group of patients.