How to take care of haematological patients in a high endemic SARS-CoV-2 region
As COVID-19 has heavily affected the population worldwide, Prof. Rambaldi shared his experience in the management of haematological patients in the high endemic COVID-19 region in Bergamo, Italy. In addition to specific guidelines and treatment recommendations, he shares the results of the small-scale use of convalescent plasma for the passive immunisation of haematological patients with COVID-19 as well as the use of siltuximab to tackle the inflammatory reaction observed in COVID-19 infected patients.
Experience in the management of haematological patients in a high endemic COVID-19 region
As generally known, the Nord of Italy is one of the most affected regions that suffered from the global COVID-19 outbreak. As a result, the Papa Giovanni XXIII Hospital in Bergamo hospitalised no less than 1,853 patients from February 20th until May 3rd 2020. The COVID-19 pandemic, evidently, also heavily affected normal daily hematologic activities in the hospital and the number of first consultations, in the outpatient clinic, that took place from February until April dropped from 546 consultations in 2019 to only 288 in 2020. In order to manage some of the most compelling patient’s problems, a telemedicine service was introduced in parallel and was of benefit to 201 haematological patients. Unfortunately, by June 14th 2020 a total number of 111 haematological patients from the Bergamo hospital were infected with COVID-19, with a high prevalence in patients with lymphoma (N=40) and chronic lymphocytic leukaemia (N=20), most likely related to the type of treatment they received prior to infection. Non-surprisingly, the mortality rate of haematological patients with a COVID-19 infection is high and lies around 25%.
As to the management of acute leukaemia in the time of a COVID-19 outbreak, Prof. Rambaldi recommends to proceed with standard induction chemotherapy with no delay, carefully consider the number and the intensity of consolidation cycles and not delaying allogeneic hematopoietic stem cell transplantation if this is indicated. Furthermore, stem cell transplanted patients should restrict their risk of exposure to infected individuals and refrain from non-necessary travel. Patients should also try to minimize the risk of infection by home isolation 14 days before the start of the transplant conditioning and all patients should be molecularly tested before the start of conditioning. In case of close contact with a person diagnosed with COVID-19, no transplant procedures will be performed within at least 14, or preferably 21, days. Also for bone marrow donors, the Italian Bone Marrow Donor Registry has developed specific guidelines and as such, all donors should be tested for SARS-CoV-2. As flight schedules are still problematic for the transportation of the graft, the collection of an autologous stem cell graft or the cryopreservation of the graft, particularly when coming from critical areas, is highly recommended. Although the transplant activity in Bergamo has been affected by the COVID-19 outbreak, this was not in a significant manner. The same is true for allogeneic stem cell graft donations, where only a slight reduction in the number of donations was observed in April and May, as compared to the number of donations in 2019.
Passive COVID-19 immunisation of patients with haematological disorders
By now, patients with a medical history of haematological disorders and a COVID-19 infection can be offered passive immunisation using the plasma of recovered COVID-19 donors. In order to be eligible for this immunisation, patients should have persistent COVID-19 symptoms for over six weeks with radiological worsening of interstitial pneumonia or rapid clinical worsening of pneumonia, a persistent SARS-CoV-2 positivity at nasopharyngeal swab or at broncho-alveolar lavage for over six weeks and a severe lymphopenia (<1500/µl) and hypoglammaglobulinemia (<500g/dl). To date, six patients in Bergamo have been treated with convalescent plasma and each of them has received three plasma infusions. Remarkably, after the administration of plasma from recovered COVID-19 donors, the CRP levels in five out of the six patients dropped and COVID-19 symptoms rapidly and completely resolved in four patients while the other two patients experienced an improvement in their symptoms. In four patients, a negativisation of the nasopharyngeal swab was noted. Although these results only represent an early experience with convalescent plasma, they might be of relevance and need to be investigated further in the future.
Addressing the cytokine storm in COVID-19
Finally, Prof. Rambaldi presented the results of the observational cohort study SISCO in which siltuximab was used to inactivate the IL-6 pathway in patients with COVID-19 respiratory failure. Aim of the study was to tackle the inflammatory reaction that is deeply involved in the tissue damage present in COVID-19 patients. In total, 30 patients were treated with siltuximab while 188 patients were included in the control arm. Of note, these were not patients with haematological malignancies, but in order to be eligible for the study, all patients must have a COVID-19 infection and require ventilator support, either non-invasive or invasive mechanical ventilation. Interestingly, the 30-day mortality risk lowered by 54% in patients who received siltuximab as compared to the patients in the control group (HR [95%CI]: 0.462 [0.221-0.965], p=0.0399). In addition, the CRP levels of these patients rapidly dropped upon siltuximab administration, indicating that the IL-6 signalling pathway is effectively inhibited by this approach.
Conclusions
COVID-19 has heavily affected the population worldwide and is a major threat for haematological patients. Specific guidelines must be implemented to protect high-risk patients, like those exposed to the most immunosuppressive treatments. The experimental use of convalescent plasma is ongoing as well as the use of drugs tackling the inflammatory reaction deeply involved in the tissue damage present in COVID-19 patients.
Reference
Rambaldi A. “How we take care of hematological patients in a high endemic SARS-CoV-2 region?” Presented at EHA 2020; Oral presentation pq282-1.
