COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey

Haematological diseases; Infectious diseases; COVID-19Malalties hematològiques; Malalties infeccioses; COVID-19Enfermedades hematológicas; Enfermedades infecciosas; COVID-19This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19

Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Càncer hematològic; Malalties infecciosesCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Cáncer hematológico; Enfermedades infecciosasCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Haematological cancer; Infectious diseasesCOVID-19 is posing a significant threat to health in vulnerable patients, such as immunocompromised patients. For hematopoietic cell transplantation (HCT) recipients and patients with hematologic malignancies it is known that COVID-19 leads to severe morbidity and high mortality as compared to the general population [1–3]. For patients treated with Chimeric Antigen Receptor T-cell (CAR-T-cell) therapy for B-cell malignancies however, descriptions of the clinical course and outcome are still limited to small case series and case reports [4–8]. CAR-T-cell therapy recipients are believed to be at high risk of poor outcomes from COVID-19 due to their severely immunocompromised state, caused by prior lymphodepleting immunochemotherapy and CAR-T-cell therapy related side effects such as B-cell depletion, hypogammaglobulinemia, and cytopenias. In order to rapidly inform the medical field on the impact of COVID-19 on CAR-T-cell therapy recipients, the EBMT Infectious Diseases Working Party and the EHA Lymphoma Group joined forces and present the clinical course of COVID-19 in the largest European cohort to date

Extracorporeal membrane oxigenation in COVID-19 patients: Results of the ECMO-COVID Registry of the Spanish Society of Cardiovascular and Endovascular Surgery

Oxigenación con membrana extracorpórea; COVID-19; Insuficiencia cardiacaExtracorporeal membrane oxygenation; COVID-19; Heart failureOxigenació amb membrana extracorpòria; COVID-19; Insuficiència cardíacaIntroducción y objetivos La oxigenación con membrana extracorpórea (ECMO) ha resultado ser una opción terapéutica en los pacientes con insuficiencia respiratoria o cardiaca severa por COVID-19. Las indicaciones y manejo de estos pacientes están aún por determinar. Nuestro objetivo es evaluar los resultados de la terapia ECMO en pacientes con COVID-19 incluidos en un registro prospectivo e intentar optimizar los resultados. Métodos En marzo de 2020 se inició un registro multicéntrico anónimo prospectivo de pacientes con COVID-19 tratados mediante ECMO veno-arterial (V-A) o veno-venosa (V-V). Se registraron las variables clínicas, analíticas y respiratorias preimplante, datos de implante y evolución de la terapia. El evento primario fue la mortalidad hospitalaria de cualquier causa y los eventos secundarios fueron la recuperación funcional y el evento combinado de recuperación funcional y mortalidad de cualquier causa a partir de los 3 meses de seguimiento tras el alta. Resultados Se analizó a un total de 365 pacientes procedentes de 25 hospitales, 347 V-V y 18 V-A (edad media de 52,7 y 49,4 años, respectivamente). Los pacientes con ECMO V-V fueron más obesos, presentaban menos fracaso orgánico diferente al pulmonar y precisaron menos terapia inotrópica previa al implante. El 33,3% y el 34,9% de los pacientes con ECMO V-A y V-V, respectivamente, fueron dados de alta del hospital (p = NS) y la mortalidad fue similar, del 56,2% y 50,9% de los casos respectivamente, la inmensa mayoría durante la ECMO y sobre todo por fracaso multiorgánico. El 14,0% (51 pacientes) permanecían ingresados. El seguimiento medio fue de 196 ± 101,7 días. En el análisis multivariante, resultaron protectores de evento primario en pacientes con ECMO V-V el peso corporal (OR 0,967; IC 95%: 0,95-0,99; p = 0,004) y la procedencia del propio hospital (OR 0,48; IC 95%: 0,27-0,88; p = 0,018), mientras que la edad (OR 1,063; IC 95%: 1,005-1,12; p = 0,032), la hipertensión arterial (3,593; IC 95%: 1,06-12,19; p = 0,04) y las complicaciones en ECMO globales (2,44; IC 95%: 0,27-0,88; p = 0,019), digestivas (OR 4,23, IC 95%: 1,27-14,07; p = 0,019) y neurológicas (OR 4,66; IC 95%: 1,39-15,62; p = 0,013) fueron predictores independientes de mortalidad. El único predictor independiente de aparición de los eventos secundarios resultó el momento de seguimiento del paciente. Conclusiones La terapia con ECMO permite supervivencias hospitalarias hasta del 50% en pacientes con COVID-19 grave. La edad, la hipertensión arterial y las complicaciones en ECMO son los predictores de mortalidad hospitalaria en pacientes con ECMO V-V. Un mayor peso corporal y la procedencia del propio hospital son factores protectores. La recuperación funcional solo se ve influida por el tiempo de seguimiento transcurrido tras el alta. La estandarización de los criterios de implante y manejo del paciente con COVID grave mejoraría los resultados y la futura investigación clínica.Background and aim: COVID-19 patients with severe heart or respiratory failure are potential candidates for extracorporeal membrane oxygenation (ECMO). Indications and management of these patients are unclear. Our aim is to describe the results of a prospective registry of COVID-19 patients treated with ECMO. Methods: An anonymous prospective registry of COVID-19 patients treated with veno-arterial (V-A) or veno-venous (V-V) ECMO was created on march 2020. Clinical, analytical and respiratory preimplantation variables, implantation data and post-implantation course data were recorded. The primary endpoint was all cause in-hospital mortality. Secondary events were functional recovery and the combined endpoint of mortality and functional recovery in patients followed at least 3 months after discharge. Results: Three hundred and sixty-six patients from 25 hospitals were analyzed, 347 V-V ECMO and 18 V-A ECMO patients (mean age 52.7 and 49.5 years respectively). Patients with V-V ECMO were more obese, had less frequently organ damage other than respiratory failure and needed less inotropic support; Thirty three percent of V-A ECMO and 34.9% of V-A ECMO were discharged (P = NS). Hospital mortality was non-significantly different, 56.2% versus 50.9% respectively, mainly during ECMO therapy and mostly due to multiorgan failure. Other 51 patients (14%) remained admitted. Mean follow-up was 196 ± 101.7 days (95%CI: 170.8-221.6). After logistic regression, body weight (OR 0.967, 95%CI: 0.95-0.99, P = 0.004) and ECMO implantation in the own centre (OR 0.48, 95%CI: 0.27-0.88, P = 0.018) were protective for hospital mortality. Age (OR 1.063, 95%CI: 1.005-1.12, P = 0.032), arterial hypertension (3.593, 95%CI: 1.06-12.19, P = 0.04) and global (2.44, 95%CI: 0.27-0.88, P = 0.019), digestive (OR 4,23, 95%CI: 1.27-14.07, P = 0.019) and neurological (OR 4.66, 95%CI: 1.39-15.62, P = 0.013) complications during ECMO therapy were independent predictors of primary endpoint occurrence. Only the post-discharge day at follow-up was independent predictor of both secondary endpoints occurrence. Conclusions: Hospital survival of severely ill COVID-19 patients treated with ECMO is near 50%. Age, arterial hypertension and ECMO complications are predictors of hospital mortality, and body weight and implantation in the own centre are protective. Functional recovery is only predicted by the follow-up time after discharge. A more homogeneous management of these patients is warranted for clinical results and future research optimization

COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey

Altres ajuts: British Society for Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT); UK NIHR Imperial College Biomedical Research Centre.This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19

COVID-19 and stem cell transplantation; results from an EBMT and GETH multicenter prospective survey

This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0-80.3) for allogeneic, and 60.6 years (7.7-81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2-292.7) in allogeneic and 24.6 months (-0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19

Ruxolitinib in refractory acute and chronic graft-versus-host disease : a multicenter survey study

Graft-versus-host disease is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. First-line treatment is based on the use of high doses of corticosteroids. Unfortunately, second-line treatment for both acute and chronic graft-versus-host disease, remains a challenge. Ruxolitinib has been shown as an effective and safe treatment option for these patients. Seventy-nine patients received ruxolitinib and were evaluated in this retrospective and multicenter study. Twenty-three patients received ruxolitinib for refractory acute graft-versus-host disease after a median of 3 (range 1-5) previous lines of therapy. Overall response rate was 69.5% (16/23) which was obtained after a median of 2 weeks of treatment, and 21.7% (5/23) reached complete remission. Fifty-six patients were evaluated for refractory chronic graft-versus-host disease. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.1% (32/56) with 3.5% (2/56) obtaining complete remission after a median of 4 weeks. Tapering of corticosteroids was possible in both acute (17/23, 73%) and chronic graft-versus-host disease (32/56, 57.1%) groups. Overall survival was 47% (CI: 23-67%) at 6 months for patients with aGVHD (62 vs 28% in responders vs non-responders) and 81% (CI: 63-89%) at 1 year for patients with cGVHD (83 vs 76% in responders vs non-responders). Ruxolitinib in the real life setting is an effective and safe treatment option for GVHD, with an ORR of 69.5% and 57.1% for refractory acute and chronic graft-versus-host disease, respectively, in heavily pretreated patients

still a concern in patients with haematological malignancies and stem cell transplant recipients-authors' response

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Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an “endemic” phase and therefore an ongoing risk within a “new normality”. These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-beta-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74-15.53; <0.001), urinary catheter (1.78; 1.03-3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25-3.88; 0.006) and time-dependent (1.04 per day; 1.00-1.07; 0.014); chronic renal failure (2.81; 1.40-5.64; 0.004) and admission from home (0.44; 0.23-0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results. Interpretation The main risk factors for CRE infections in hospitals with high incidence included previous coloni-zation, urinary catheter and exposure to broad spectrum antibiotics

Upper and/or lower respiratory tract infection caused by human metapneumovirus after allogeneic hematopoietic stem cell transplantation.

peer reviewed[en] PATIENTS AND METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allogeneic stem cell transplantation (allo-HCT). RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases