International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

COVID-19 in hematopoietic cell transplant recipients.

In this study, we aim to report the outcome of COVID-19 in hematopoietic cell transplant (HCT) recipients. HCT recipients (n = 32) with hematological disease and hospitalized for COVID-19 were included in the study. A cohort of age and comorbid disease-matched hospitalized COVID-19 patients with hematological malignancy but not underwent HCT (n = 465), and another cohort of age and comorbid disease-matched hospitalized COVID-19 patients without cancer (n = 497) were also included in the study for comparison. Case fatality rate (CFR) was 5.6% in patients without cancer, 11.8 in patients with hematological malignancy and 15.6% in HCT recipients. The CFR in HCT recipients who were not receiving immunosuppressive agents at the time of COVID-19 diagnosis was 11.5%, whereas it was 33% in HCT recipients who were receiving an immunosuppressive agent at the time of COVID-19 diagnosis. In conclusion, our study reveals that for the current pandemic, HCT recipients, especially those receiving immunosuppressive drugs, constitute a special population of cancer patients.

Mesenchymal stem cell transfusion: Possible beneficial effects in COVID-19 patients.

SARS-CoV-2 attaches to the angiotensin-converting enzyme 2 (ACE-2) receptor on human cells. The virus causes hypercytokinemia, capillary leak, pulmonary edema, acute respiratory distress syndrome, acute cardiac injury, and leads to death. Mesenchymal stem cells (MSCs) are ACE-2 negative cells; therefore, can escape from SARS-CoV-2. MSCs prevent hypercytokinemia and help the resolution of the pulmonary edema and other damages occurred during the course of COVID-19. In addition, MSCs enhance the regeneration of the lung and other tissues affected by SARS-CoV-2. The case series reported beneficial effect of MSCs in COVID-19 treatment. However, there are some concerns about the safety of MSCs, particularly referring to the increased risk of disseminated intravascular coagulation, and thromboembolism due to the expression of TF/CD142. Prospective, randomized, large scale studies are needed to reveal the optimum dose, administration way, time, efficacy, and safety of MSCs in the COVID-19 treatment.

Patients with hematologic cancers are more vulnerable to COVID-19 compared to patients with solid cancers.

Previous studies reported that COVID-19 patients with cancer had higher rates of severe events such as intensive care unit (ICU) admission, mechanical ventilation (MV) assistance, and death during the COVID-19 course compared to the general population. However, no randomized study compared the clinical course of COVID-19 in patients with hematologic cancers to patients with solid cancers. Thus, in this study, we intend to reveal the outcome of COVID-19 in hematologic cancer patients and compare their outcomes with COVID-19 patients with solid cancers. The data of 926 laboratory-confirmed COVID-19 patients, including 463 hematologic cancer patients and an age-gender paired cohort of 463 solid cancer patients, were investigated retrospectively. The frequencies of severe and critical disease, hospital and ICU admission, MV assistance were significantly higher in hematologic cancer patients compared with the solid cancer patients (p = 0.001, p = 0.045, p = 0.001, and p = 0.001, respectively). The hospital stay was longer in patients with hematologic cancers (p = 0.001); however, the median ICU stay was 6 days in both groups. The case fatality rate (CFR) was 14.9% in patients with hematologic cancers, and it was 4.8% in patients with solid cancers, and there was a statistically significant difference regarding CFR between groups (p = 0.001). Our study revealed that COVID-19 patients with hematologic cancers have a more aggressive course of COVID-19 and have higher CFR compared to COVID-19 patients with solid cancers and support the increased susceptibility of patients with hematologic cancers during the outbreak.

Convalescent plasma therapy in patients with COVID-19.

INTRODUCTION: Passive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19. METHOD: The data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively. RESULTS: Duration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6-10 days, 11-15 days) (p=0.001). CONCLUSION: CP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.

COVID-19 clinical course and blood groups: Turkish population-based study

Background/aim: SARS-CoV-2 enters the cell through the binding of the S glycoprotein on the surface of the virus to the angiotensin- converting enzyme 2 (ACE-2) in the host cells and also SARS-CoV S protein binding to ACE-2 was inhibited by anti-A antibodies. The aim of the study was to investigate the relationship between blood groups and the course of COVID-19 in Turkey. Materials and methods: Laboratory confirmed COVID-19 patients aged 18 and over (n = 39.850) were randomized in age and sex- matched groups according to blood groups. Results: Advanced age, male sex and blood group A were found to be related with increased rate of intensive care unit (ICU) admission (OR = 1.089, 95% CI: 1.085­1.093 for age; OR = 1.963, 95% CI: 1.737­2.218 for male sex; OR = 1.216, 95% CI: 1.023­1.446 for blood group A). When blood group O individuals were compared to non-O individuals, no significant difference was observed regarding the rate of hospital and ICU admission, mechanical ventilation (MV) support, length of hospital and ICU stay, and case fatality rate (CFR). The CFR in patients with blood group A, B, O, and AB were 2.6%, 2.2%, 3.1%, and 2.3%, respectively. There were no significant differences between Rh-negative and positive patients regarding the rate of hospital and ICU admission (p = 0.280 and p = 0.741, respectively), also the rate of MV support and CFR was similar (p = 0.933 and p = 0.417). Conclusion: Our study revealed that ABO and Rh blood groups do not have any impact on the rate of hospital admission, hospital and ICU stay, MV support, and CFR.

The outcome of COVID-19 in patients with hematological malignancy.

In this study, we aim to report the outcomes for COVID-19 in patients with hematological malignancy in Turkey. Data from laboratory-confirmed 188 897 COVID-19 patients diagnosed between 11 March 2020 and 22 June 2020 included in the Republic of Turkey, Ministry of Health database were analyzed retrospectively. All COVID-19 patients with hematological malignancy (n = 740) were included in the study and an age, sex, and comorbidity-matched cohort of COVID-19 patients without cancer (n = 740) at a 1:1 ratio was used for comparison. Non-Hodgkin lymphoma (30.1%), myelodysplastic syndrome (19.7%), myeloproliferative neoplasm (15.7%) were the most common hematological malignancies. The rates of severe and critical disease were significantly higher in patients with hematological malignancy compared with patients without cancer (P = .001). The rates of hospital and intensive care unit (ICU) admission were higher in patients with hematological malignancy compared with the patients without cancer (P = .023, P = .001, respectively). The length of hospital stay and ICU stay was similar between groups (P = .7, P = .3, retrospectively). The rate of mechanical ventilation (MV) support was higher in patients with hematological malignancy compared with the control group (P = .001). The case fatality rate was 13.8% in patients with hematological malignancy, and it was 6.8% in the control group (P = .001). This study reveals that there is an increased risk of COVID-19-related serious events (ICU admission, MV support, or death) in patients with hematological malignancy compared with COVID-19 patients without cancer and confirms the high vulnerability of patients with hematological malignancy in the current pandemic.

Outcome of COVID-19 in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors.

INTRODUCTION: In this study, we aim to report the outcome of COVID-19 in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitor (TKI). METHOD: The data of 16 laboratory-confirmed COVID-19 patients with CML receiving TKI and age, gender, and comorbid disease matched COVID-19 patients without cancer at a 3/1 ratio (n = 48), diagnosed between March 11, 2020 and May 22, 2020 and included in the Republic of Turkey, Ministry of Health database, were analyzed retrospectively. RESULTS: The rates of intensive care unit (ICU) admission, and mechanical ventilation (MV) support were lower in CML patients compared to the control group, however, these differences did not achieve statistical significance (p = 0.1, and p = 0.2, respectively). The length of hospital stay was shorter in CML patients compared with the control group; however, it was not statistically significant (p = 0.8). The case fatality rate (CFR) in COVID-19 patients with CML was 6.3%, and it was 12.8% in the control group. Although the CFR in CML patients with COVID-19 was lower compared to the control group, this difference did not achieve statistical significance (p = 0.5). When CML patients were divided into 3 groups according to the TKI, no significant difference was observed regarding the rate of ICU admission, MV support, CFR, the length of stay in both hospital and ICU (all p > 0.05). CONCLUSION: This study highlights that large scale prospective and randomized studies should be conducted in order to investigate the role of TKIs in the treatment of COVID-19.

Convalescent plasma therapy in patients with COVID-19.

There are currently no licensed vaccines or therapeutics for COVID-19. Anti-SARS CoV-2 antibody-containing plasmas, obtained from the recovered individuals who had confirmed COVID-19, have been started to be collected using apheresis devices and stored in blood banks in some countries in order to administer to the patients with COVID-19 for reducing the need of intensive care and the mortality rates. Therefore, in this review, we aim to point out some important issues related to convalescent plasma (CP) and its use in COVID-19. CP may be an adjunctive treatment option to the anti-viral therapy. The protective effect of CP may continue for weeks and months. After the assessment of the donor, 200-600 mL plasma can be collected with apheresis devices. The donation interval may vary between countries. Even though limited published studies are not prospective or randomized, until the development of vaccines or therapeutics, CP seems to be a safe and probably effective treatment for critically ill patients with COVID-19. It could also be used for prophylactic purposes but the safety and effectiveness of this approach should be tested in randomized prospective clinical trials.

Extracorporeal blood purification treatment options for COVID-19: The role of immunoadsorption.

The activation of the innate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.