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1.
A 16-month-long experience of COVID-19 in allogeneic haematopoietic stem cell transplantation recipients: An SFGM-TC multicentre cohort study
Xhaard, A., Xhaard, C., Rubio, M. T., Berceanu, A., Botella-Garcia, C., Coman, T., Tavernier, E., Labussière-Wallet, H., Chevallier, P., Legrand, F., et al
British journal of haematology. 2023
Abstract
This 16-month-long multicentre retrospective study of 225 allogeneic haematopoietic stem cell transplantation (alloHSCT) recipients with COVID-19 examines risk factors for severity and mortality, describing the successive waves of infections (from March to June 2020 and from August 2020 to June 2021). We confirm the negative role of low respiratory tract disease and immunosuppressive treatment. We highlight significantly lower percentages of severe forms and COVID-19-related mortality during the second wave. Monthly comparative evolution of cases in alloHSCT recipients and in the French population shows a higher number of cases in alloHSCT recipients during the first wave and a decrease from February 2021.
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2.
Pre-exposure prophylaxis with tixagevimab/cilgavimab (AZD7442) prevents severe SARS-CoV-2 infection in recipients of allogeneic hematopoietic stem cell transplantation during the Omicron wave: a multicentric retrospective study of SFGM-TC
Jondreville, L., D'Aveni, M., Labussière-Wallet, H., Le Bourgeois, A., Villate, A., Berceanu, A., Bezsera, S. M., Thiebaut, A., Boissard-Simonet, M., Legrand, M., et al
Journal of hematology & oncology. 2022;15(1):169
Abstract
Since the emergence of the Omicron variant of SARS-CoV-2, though considered less virulent, hospitalization and death rates among immunocompromised patients remain high, especially for poor responders to vaccination. We conducted a retrospective multicentric study to evaluate pre-exposure prophylaxis with AZD7442 (tixagevimab/cilgavimab) for preventing COVID-19 in adult allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Among the 161 patients of our cohort, 22 (14%) contracted COVID-19 after a median follow-up of 105 days, but no severe form was observed. Only one major adverse event was reported: an acute coronary syndrome, resolved without sequelae. Pending randomized controlled trial results, our data support the use of AZD7442 as pre-exposure prophylaxis for COVID-19 during Omicron wave in allo-HSCT patients who failed to develop humoral immunity to vaccination, to prevent severe and potentially lethal forms of SARS-CoV-2 infection.
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3.
B-cell aplasia is the most powerful predictive marker for poor humoral response after BNT162b2 mRNA SARS-CoV-2 vaccines in recipients of allogeneic hematopoietic stem cell transplantation
Jullien, M., Bourgeois, A. L., Coste-Burel, M., Peterlin, P., Garnier, A., Rimbert, M., Imbert, B. M., Gouill, S. L., Moreau, P., Mahe, B., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Little is known on the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, a few studies have reported that adequate protection could be provided to this population. OBJECTIVE(S): The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. STUDY DESIGN Specific anti Spike (S) antibody responses were assessed in a cohort of 117 Allo-HSCT recipients after two injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between Allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment and levels of CD4(+)and CD8(+) T-cells, B-cells and NK-cells at the time of V1. RESULTS Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titre. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T-cell and B-cell counts as well as ongoing I/C treatment and a haploidentical donor were characteristic of non-humoral responders. However, multiparameter analysis showed that B-cell aplasia was the only factor predicting the absence of a specific immune response (Odd Ratio 0.01, 95%CI [0.00 - 0.10], p <10(-3)). Indeed, the rate of humoral response was 9.1% in patients with B-cell aplasia, vs 95.9% in patients with a B-cell count higher than 0 (p<10(-9)). CONCLUSION(S): These results advocate for the prescription of anti-SARS-CoV-2 vaccination in Allo-HSCT recipients as early as peripheral B-cell levels can be detected, suggesting also a need for a close monitoring of B-cell reconstitution after Allo-HSCT.
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4.
SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine
Clémenceau, B., Guillaume, T., Coste-Burel, M., Peterlin, P., Garnier, A., Le Bourgeois, A., Jullien, M., Ollier, J., Grain, A., Béné, M. C., et al
Vaccines. 2022;10(3)
Abstract
BACKGROUND At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. METHODS SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4(+) and CD8(+) T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. RESULTS A strong TNF-α(+) response from SARS-CoV-2-specific CD4(+) T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). CONCLUSIONS T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo-HSCT recipients.
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5.
Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients
Clémenceau, B., Le Bourgeois, A., Guillaume, T., Coste-Burel, M., Peterlin, P., Garnier, A., Jullien, M., Ollier, J., Grain, A., Béné, M. C., et al
Cells. 2022;11(19)
Abstract
A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.
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6.
Effectiveness of a third dose of BNT162b2 anti-SARS-CoV-2 mRNA vaccine over a 6-month follow-up period in allogenic hematopoietic stem cells recipients
Chevallier, P., Jullien, M., Peterlin, P., Garnier, A., Le Bourgeois, A., Coste-Burel, M., Béné, M. C., Guillaume, T.
Hematological oncology. 2022
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Abstract
This study reports the effectiveness of three injections of BNT162b2 anti-SARS-CoV-2 mRNA vaccine in 141 Allo-HSCT recipients with a median follow-up of 6 months post-third shot. We demonstrate a long-term high protection of Allo-HSCT recipients since only 2 infections and one death related to COVID-19 occurred.
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7.
Effective Letermovir Prophylaxis of CMV infection post allogeneic hematopoietic cell transplantation: Results from the French temporary authorization of use compassionate program
Beauvais, D., Robin, C., Thiebaut, A., Alain, S., Coiteux, V., Ducastelle-Lepretre, S., Marçais, A., Ceballos, P., Xhaard, A., Redjoul, R., et al
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2022;148:105106
Abstract
We report the results of the French Temporary Authorization of Use (ATU) compassionate program of letermovir for primary prophylaxis conducted in 21 transplant centers. Patients were CMV seropositive allogeneic hematopoietic cell transplantation recipients and at high risk for CMV infection. Primary prophylaxis was defined as initiation of letermovir between day 0 and day +28 post-transplant. Between November 2017 and January 2019, 96 patients with a median age of 56 years received letermovir and follow-up data were available for 78 patients. The median time from transplant to letermovir initiation was 4 days, and the median duration of exposure to letermovir was 78 days, with 57 patients still on treatment at the cutoff date. Letermovir was temporarily discontinued in 4 patients (5.1%) and stopped in 39 patients (50.0%), in most cases due to planned end of treatment (n = 16, 20.5%). Fifteen patients (19.2%) each presented one positive CMV PCR, in median 13 days after letermovir initiation. Clinically significant CMV infection was reported in 5 patients (6.4%). No CMV disease was reported. At least one adverse drug reaction was reported for 12 patients (15.4%). In this early access program, letermovir was effective with comparable results of the phase 3 study with a low rate of clinically significant CMV infection, including in patients who were at high-risk for CMV infection.
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Safety and immunogenicity of a first dose of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem-cells recipients
Chevallier, P., Coste-Burel, M., Le Bourgeois, A., Peterlin, P., Garnier, A., Béné, M. C., Imbert, B. M., Drumel, T., Le Gouill, S., Moreau, P., et al
EJHaem. 2021
Abstract
This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer-BioNTech) in 112 Allo-HSCT patients. Antibody response to SARS-CoV-2 spike protein receptor-binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non-randomized control arm of 26 healthy controls. This study shows that a first dose of SARS-CoV-2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p < 0.001). Factors influencing the absence of response in patients were recent transplantation (<2 years), lymphopenia (<1 × 10(9)/L) and immunosuppressive treatment or chemotherapy at the time of vaccination.
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Scoring system for clinically significant CMV infection in seropositive recipients following allogenic hematopoietic cell transplant: an SFGM-TC study
Beauvais, D., Drumez, E., Blaise, D., Peffault de Latour, R., Forcade, E., Ceballos, P., Uyttebroeck, A., Labussière, H., Nguyen, S., Bourhis, J. H., et al
Bone marrow transplantation. 2021;56(6):1305-1315
Abstract
In order to identify cytomegalovirus (CMV)-seropositive patients who are at risk of developing CMV infection following first allogeneic hematopoietic cell transplantation (allo-HCT), we built up a scoring system based on patient/donor characteristics and transplantation modalities. To this end, 3690 consecutive patients were chronologically divided into a derivation cohort (2010-2012, n = 2180) and a validation cohort (2013-2014, n = 1490). Haploidentical donors were excluded. The incidence of first clinically significant CMV infection (CMV disease or CMV viremia leading to preemptive treatment) at 1, 3, and 6 months in the derivation cohort was 13.8%, 38.5%, and 39.6%, respectively. CMV-seropositive donor, unrelated donor (HLA matched 10/10 or HLA mismatched 9/10), myeloablative conditioning, total body irradiation, antithymocyte globulin, and mycophenolate mofetil significantly and independently affected the incidence of 3-month infection. These six factors were selected to build up the prognostic model. Four risk groups were defined: low, intermediate-low, intermediate-high, and high-risk categories, with a 3-month predicted incidence of first clinically significant CMV infection in the derivation cohort of 22.2%, 31.1%, 45.4%, and 56.9%, respectively. This score represents a framework for the evaluation of patients who are at risk of developing clinically significant CMV infection following allo-HCT. Prospective studies using this score may be of benefit in assessing the value of anti-CMV prophylaxis in well-defined patient cohorts.
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10.
Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant
Le Bourgeois, A., Coste-Burel, M., Guillaume, T., Peterlin, P., Garnier, A., Béné, M. C., Chevallier, P.
JAMA network open. 2021;4(9):e2126344