RECOMMENDATIONS OF NATIONAL CONSULTANTS ON VACCINATION AGAINST SARS-COV-2 IN CHILDREN WITH MALIGNANCIES OR AFTER HEMATOPOIETIC CELL TRANSPLANTATION.

With accumulating data on severe course of SARS-CoV-2/COVID-19 infection in children, it should be taken into account that immunocompromised patients are at increased risk of complications and death due to this disease. Currently vaccination is the only option to prevent the disease. Nowadays more and more data are coming on vaccination in children and in patients with immune deficiencies. In this paper, Polish National Consultants in pediatric oncology and hematology and clinical immunology present recommendations on vaccination in children with malignancies or after hematopoietic cell transplantation. These recommendations are based on ECIL-9 guidelines, adopted to national situation and updated with the latest information. With the fast changing knowledge and statements provided by Center for Disease Control (CDC), Food and Drug Administration (FDA) and European Med-icines Agency (EMA), such recommendations need to be regularly updated. Nevertheless, individual risk/benefit ratio should be always assessed for each patient, particularly in the case of the risk of poor immunological response to immunization.Copyright © 2021, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

Use of convalescent plasma in patients with COVID-19

Introducton: We wished to evaluate the clinical effectiveness of convalescent plasma (CP) in coronavirus disease 2019 (COVID-19) patients treated in hospitals in the Kuyavian-Pomeranian Voivodeship, including the impact of treatment duration and CP antibody titer on the course of hospitalization and patient survival in relation to other risk factors. Material(s) and Method(s): This was a retrospective analysis of clinical data of CP use in hospitals in the Kuyavian-Pomeranian Voivodeship. Result(s): A total of 3,596 patients had available clinical data. In 59% of patients, CP was administered during the initial 24 hours of hospitalization (median: 1 day, range 1-49). In cured patients, hospital length of stay correlated with time of CP administration (p <0.001), i.e. the sooner the COVID-19 convalescent plasma (CCP) was administered, the shorter the hospitalization. Overall survival in analyzed COVID-19 patients was 78.3%, and it was better when CP was administered during the first day of hospitalization (79.9% vs. 86.8%, p = 0.057), in younger patients (91.0% vs. 76.2% for patients <50 years and older, respectively;p <0.001);in patients not requiring invasive ventilation (78.7% vs. 26.9%, p <0.001), in good performance status patients (92.5% vs. 81.0% and 68.6% in patients in moderate and poor performance status, respectively;p <0.001);and in patients without comorbidities (88.6% vs. 75.9%, p <0.001). In turn, blood group and titers of antibodies against severe acute respiratory syndrome coronavirus 2 in CP had no impact on survival. In multivariate analysis, the following factors increased the risk of death from COVID-19: general clinical status at admission (poor > moderate > good), comorbidities, mechanical ventilation required. Risk of death was decreased in younger patients (continuous variable), while administration of CP within the first day of hospitalization had borderline significance (p = 0.077). The use of CP was a safe therapeutic approach. Mild reactions were reported after just 5/9,356 (0.05%) transfusions. Conclusion(s): The early administration of CP had a beneficial effect on the clinical course of treatment in COVID-19 patients. Copyright © 2022 The Polish Society of Haematologists and Transfusiologists, Insitute of Haematology and Transfusion Medicine. All rights reserved.

The national recommendation for the covid-19 prevention and control in pediatric units of hematology and oncology, hematopoietic cell transplantation units and respective outpatient clinics: Guidelines of polish society of pediatric oncology and hematology

In December 2019 novel coronavirus SARS-CoV-2 has been identified. It is responsible for a pandemic COVID-19 disease with a risk of fatal outcome ranging 2% to 6%. Pediatric patients with cancer during intensive oncological treatment are considered as a risk group of unfavorable outcomes because of profound immunosuppression. Based on literature and the national local experiences, the Polish Society of Pediatric Oncology and Hematology provided with the national recommendation for the COVID-19 prevention and control in pediatric hematology and oncology, hematopoietic cell transplantation units and well as respective outpatient clinics. Copyright © 2020, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

Improved outcomes over time and higher mortality in CMV seropositive allogeneic HCT patients with COVID-19: A study from the EBMT registry

Background: COVID-19 has been associated with high mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Aim: To study outcome over time and identify risk factors for mortality in patients reported to the EBMT registry. Methods: 776 allo-HCT patients reported during the first 21 months of the pandemic up until Nov. 2021 were included. Cox regression models were produced to assess risk factors for mortality. Results: The median age was 49.4 years (min-max;1.0 - 80.7). The median time from HCT to COVID-19 diagnosis was 14.1 (0.0-292.7) months during the first period (February 28 - July 31, 2020), 24.4 (0.1-287.6) months during the 2nd (August 1, 2020 - January 31, 2021), and 24.8 (0.1-324.5) months during the 3rd (February 1 - November 30, 2021). 110/776 (14.2%) patients died a median of 21.5 days after diagnosis of SARS-CoV-2 infection. Children had a significantly lower mortality than adults. In multivariate analysis, increasing age (HR 1.27 (95% CI 1.11-1.44;p = .0004), worse performance status (HR 1.48 (1.32-1.65;p <.0001), contracting COVID-19 within the first 30 days after HCT (HR 4.69 (2.44-9.02);p <.0001), ongoing immunosuppression (HR 2.05 (1.20-3.50);p = .009), and recipient CMV seropositivity (HR 2.38 (1.25-4.52);p = .008) had negative impact on overall survival while patients contracting COVID-19 in the 2nd or 3rd period had higher overall survival (p = .0003). Conclusion: Although the outcome of COVID-19 has improved, patients having risk factors still showed high mortality and preventive measures have to be taken.

Vaccinations following CAR-T cell therapy: summary of reported cases and state-of-the-art review of current recommendations

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is a modern breakthrough technology used in the treatment of B-lineage lymphoid malignancies. These malignancies include acute lymphoblastic leukemia, non-Hodgkin lymphoma, and plasma cell disorders. CAR-T therapy combines cellular therapy, gene therapy, and individualized therapy. The objective of this paper was to review the latest clinical knowledge, and summarize the reported data pertaining to vaccinations in patients after CAR-T therapy. Material and methods: We carried out a review of published original studies as indexed in PubMed, and a review of s presented during major hematology meetings. Results: Overall, 22 original studies were reviewed and considered suitable for analysis regarding the efficacy of vaccinations for patients who had received CAR-T therapy. Data was divided into three groupings: the efficacy of vaccination against coronavirus disease 2019 (COVID-19)/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2);the efficacy of vaccination against influenza;and the efficacy of post-CAR-T immunization persistence of vaccination performed before CAR-T therapy. Humoral and cellular response to SARS-CoV-2 vaccination was positive for 36.5% and 72.2% of patients, respectively. The positive response to the influenza vaccine was 40% when administered prior to CAR-T therapy, as opposed to 31% after. Seroprotection for vaccine-preventable infections within 3-6 months after CAR-T was comparable to that of the general population, although it was determined to be less effective against specific pathogens (S. pneumoniae, B. pertussis, H. influenzae) in most patients. Conclusions: In cases of incomplete immune reconstitution, there is a high likelihood of a limited response to vaccination. Regarding the SARS-CoV-2/COVID-19 vaccine, T-cell-induced protection is relatively significant. Therefore, B-cell aplasia is not a contraindication for vaccination in CAR-T patients. The consensus of European Society of Blood and Marrow Transplantation/European Hematology Association experts is that vaccination after CAR-T therapy is beneficial in order to reduce the rates of infection, and eventually to improve clinical course. Copyright © 2022 The Polish Society of Haematologists and Transfusiologists, Insitute of Haematology and Transfusion Medicine. All rights reserved

Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations

Infections are still one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper was the presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation with Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing (European Conference on Infections in Leukemia (ECIL) and European Society of Blood and Marrow Transplantation (EBMT) guidelines, as well as the results of a survey performed among all Polish transplant centers, were the background material for the working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on the principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.

COVID-19 in Children Following Hematopoietic Cell Transplantation: A Multinational Study of the European Bone Marrow Transplantation Society (EBMT) and the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH)

Introduction COVID-19 is usually a mild disease in immunocompetent children, with ~1% requiring intensive care unit (ICU) admission and <0.1% mortality. Data on its course in children following hematopoietic cell transplantation (HCT) is limited. Methods Data on children following HCT who developed COVID-19 (diagnosed by positive SARS-CoV-2 PCR on respiratory tract samples) during 3.2020-4.2021 were prospectively collected by EBMT and GETH, including demography, HCT data, COVID-related manifestations, ICU admission and mortality. Factors associated with worse outcomes (ICU admission or mortality) were characterized. Results Sixty-two children (34 boys;median age 9;min-max;0.7-17 years) were reported from 27 centers, 16 countries;57 (92%) following allogeneic and 5 (8%) following autologous HCT. Underlying diseases were acute leukemia (23;37%), inherited disorders (9;15%), hemoglobinopathies (7;11%), solid tumor (6;10%), bone marrow failure (5;8%), other malignant (8;13%) and non-malignant (4;6%) diseases. Five (8%) children had high blood pressure;6 (10%) had underlying lung pathology. The median time from the most recent HCT to COVID was 5 months (min-max;0-169). The stem cell source was bone marrow (33);peripheral (22) or cord blood (1). Among the patients with information available, 34 (62%) underwent in-vivo T cell depletion, 20 (33%) received corticosteroids, and 36 (60%) other immunosuppressant drugs(s) within two months prior to and after the COVID-19 episode. The presence of acute grade 2-4 or chronic graft versus host disease (GVHD) was reported in 12/54 (23%) and 8/51 (16%) children, respectively. Clinical presentation (n=57) included fever (28;49%), cough (18;32%), diarrhea (8;14%), upper respiratory tract disease (as rhinorrhea, sinusitis, otitis, or pharyngitis;12;21%);six (10%) required oxygen to maintain oxygen saturation above 92%;20 children (35%) were asymptomatic. The median time from symptoms onset to COVID diagnosis was 1 day (-43-40). Sixty-three percent of patients were hospitalized;43% due to COVID. The proportion of children with neutropenia or lymphocytopenia (<500 cells/mm 3) was 75% and 73%, respectively. Sixteen children (26%) had evidence of viral (n=10), bacterial (n=6) or fungal (n=2) coinfections. The median time from COVID diagnosis to the last follow-up in alive patients was 69 days (min-max;2 - 294). Six (10%) children who developed COVID at a median 6.5 (min-max;2- 16) months following allo-HCT (median age 6 years;5 boys) required ICU care within a median 6 (min-max;-5-15) days after diagnosis. All of them were neutropenic, received steroids, and other immunosuppressive drugs at COVID diagnosis;5 had undergone in-vivo T cell depletion;5 were lymphocytopenic, 5 had GVHD (2 acute and 3 chronic);3 received non-invasive and 2 invasive ventilation. Three children had viral or bacterial coinfections. Three children died. Six (10%) children (5 boys, median age 10.5 years;min-max;4-13) who developed COVID at median 2 (min-max;0-147) months following allo-HCT died within median 35 days (min-max;5-54) after diagnosis. One had high blood pressure, and none suffered from underlying lung pathology. At the time of COVID, 3 were neutropenic, 2 lymphocytopenic;4 had GVHD (2 acute, 2 chronic);3 received steroids and 4 immunosuppressive drugs. Two had viral or bacterial coinfections. Five had positive SARS-CoV-2 PCR at the time of death. In 3, COVID was the primary cause of death. We compared nine children with the worse outcomes to 53 children with benign course. Among patients alive at 100-day post HCT, the probability of worse outcomes was higher in patients with vs. without chronic GVHD (Figure). No other significant differences were observed in demographic, underlying disease, and HCT-related characteristics. Compared to adults following HCT (Ljungman, Leukemia 2021), children had: - Shorter median time from HCT to COVID diagnosis, 5 vs 18 months;- Higher proportion of asymptomatic infections, 35% vs 9%;- Lower proportion of those who required oxygen, 10% vs 35%;- Lower all-cause mortality, 10% vs 29%. Conclusions Children following HCT with COVID-19 have a higher risk of ICU admission and mortality compared to immune competent children. The presence of chronic GVHD at COVID diagnosis was associated with worse outcomes. COVID course following HCT is milder in children compared to adults. [Formula presented] Disclosures: Averbuch: Takeda: Consultancy;Pfizer: Consultancy;GSK: Speakers Bureau. De La Camara: Roche: Consultancy;IQONE: Consultancy. Corbacioglu: Gentium/Jazz Pharmaceuticals: Consultancy, Honoraria. Mikulska: Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Speakers Bureau;MSD: Speakers Bureau;Janssen: Speakers Bureau;Biotest: Speakers Bureau. Kulagin: Roche: Speakers Bureau;Sanofi: Speakers Bureau;Generium: Speakers Bureau;Biocad: Research Funding;Apellis: Research Funding;Alexion: Research Funding;X4 Pharmaceuticals: Research Funding;Novartis: Speakers Bureau;Johnson & Johnson: Speakers Bureau;Pfizer: Speakers Bureau. Cesaro: Sobi: Membership on an entity's Board of Directors or advisory committees;Gilead: Speakers Bureau. Lawson: Alexion: Honoraria. Kroeger: Neovii: Honoraria, Research Funding;Sanofi: Honoraria;Jazz: Honoraria, Research Funding;Celgene: Honoraria, Research Funding;Riemser: Honoraria, Research Funding;Gilead/Kite: Honoraria;AOP Pharma: Honoraria;Novartis: Honoraria. Styczynski: MSD, Pfizer, Giled, TEVA, Jazz, Novartis: Honoraria, Speakers Bureau. Ljungman: Takeda: Consultancy, Other: Endpoint committee, speaker;Enanta: Other: DSMB;Janssen: Other: Investigator;OctaPharma: Other: DSMB;Merck: Other: Investigator, speaker;AiCuris: Consultancy.

Epidemiology and prevention strategies of SARS-CoV-2 infection in pediatric hematology and oncology centers in Poland

Introduction: Epidemiological analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections in pediatric hematology and oncology (PHO) and hematopoietic cell transplant (HCT) centers in a Polish nationwide study, as well as analysis of the preventive strategies in these centers. Methods: All of the 18 PHO/HCT centers participated in eight surveys and questionnaires conducted over the first 5 months of the SARS-CoV-2/ coronavirus disease 2019 (COVID-19) pandemic in Poland. Epidemiological data were collected at eight regular time points, and the strategy of preventive management was done once after 4 months of the pandemic. Results: During this analyzed period, eight patients were positive for SARS-CoV-2. The estimated incidence of SARS-CoV-2 positivity in Polish PHO/HCT centers was 0.5%. After exclusion of HCT patients (with one patient being infected), the estimated incidence of SARSCoV-2 positivity was between 0.5 and 0.6%. In all but one case, the course of COVID-19 was asymptomatic or mild, and it was moderate in one case. None of them developed SARS or respiratory insufficiency, none of them required treatment in the intensive care unit (ICU), and no patient died due to SARS-CoV-2 infection. As of July 1, parents staying in the hospital together with their children were regularly tested for the virus in 13 centers. Asymptomatic healthcare personnel were regularly tested for the virus in seven centers. Conclusions: The estimated incidence of SARS-CoV-2 infection among PHO/HCT patients is lower than in Western Europe;however, these patients cannot be regarded as a low-risk group. The low COVID-19 incidence should be interpreted as a result of strictly and continuously implemented detailed preventive measures in the PHO/HCT wards and in hospitals.