Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant | Stem Cell Transplantation | JAMA Network Open | JAMA Network
[Skip to Navigation]
Sign In
Figure.  Anti–SARS-CoV-2 Titers After the First and Second Vaccine Injections
Anti–SARS-CoV-2 Titers After the First and Second Vaccine Injections

Box plots show anti–SARS-CoV-2 spike protein receptor titers after the first and the second vaccine injections. Lines within boxes denote medians, error bars denote 95% CIs, circles denote data for individual patients. Comparisons are between patients for whom follow-up after allogeneic hematopoietic stem cell transplant was less than 1 year vs between 1 and 2 years vs more than 2 years.

Table.  Patient Characteristics and Results of Serological Tests After Dose 1 and Dose 2
Patient Characteristics and Results of Serological Tests After Dose 1 and Dose 2
1.
García-Suárez  J, de la Cruz  J, Cedillo  Á,  et al; Asociación Madrileña de Hematología y Hemoterapia (AMHH).  Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.   J Hematol Oncol. 2020;13(1):133. doi:10.1186/s13045-020-00970-7PubMedGoogle ScholarCrossref
2.
Xhaard  A, Xhaard  C, D’Aveni  M,  et al.  Risk factors for a severe form of COVID-19 after allogeneic haematopoietic stem cell transplantation: a Société Francophone de Greffe de Moelle et de Thérapie cellulaire (SFGM-TC) multicentre cohort study.   Br J Haematol. 2021;192(5):e121-e124. doi:10.1111/bjh.17260PubMedGoogle ScholarCrossref
3.
Walsh  EE, Frenck  RW  Jr, Falsey  AR,  et al.  Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates.   N Engl J Med. 2020;383(25):2439-2450. doi:10.1056/NEJMoa2027906PubMedGoogle ScholarCrossref
4.
Chevallier  P, Coste-Burel  M, Le Bourgeois  A,  et al  Safety and immunogenicity of a first dose of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem-cells recipients.   EJHaem. Published online June 1, 2021. doi:10.1002/jha2.242PubMedGoogle Scholar
5.
Boyarsky  BJ, Werbel  WA, Avery  RK,  et al.  Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients.   JAMA. 2021;325(21):2204-2206. doi:10.1001/jama.2021.7489PubMedGoogle ScholarCrossref
6.
Barrière  J, Chamorey  E, Adjtoutah  Z,  et al.  Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors.   Ann Oncol. 2021;32(8):1053-1055. doi:10.1016/j.annonc.2021.04.019PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Research Letter
    Hematology
    September 14, 2021

    Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant

    Author Affiliations
    • 1Hematology Department, Nantes University Hospital, Nantes, France
    • 2Virology Department, Nantes University Hospital, Nantes, France
    • 3Institut National de al Santé et de la Recherche Médicale, Unité Mixte Recherche 1232, Centre de Recherche en Cancérologie et Immunologie Nantes Angers Institut de Recherche en Santé de l’Université de Nantes, University of Nantes, France
    • 4Hematology Biology, Nantes University Hospital, Nantes, France
    JAMA Netw Open. 2021;4(9):e2126344. doi:10.1001/jamanetworkopen.2021.26344
    Introduction

    COVID-19, which is due to infection with SARS-CoV-2, results in poor outcomes in patients with hematologic cancers (approximately 40% mortality rate).1,2 The efficacy of anti-SARS-CoV-2 mRNA vaccines has been successfully demonstrated in healthy populations3 and also has been reported in immunocompromised patients. Recently, we showed that a first injection of the BNT162b2 (Pfizer-BioNTech) vaccine induced an antibody response in 55% of 112 allogeneic hematopoietic stem cell transplant (HSCT) recipients.4 Here, we document the antibody response to a second dose of BNT162b2 vaccine in an extended cohort of 117 patients.

    Methods

    This single-center cohort study enrolled allogeneic HSCT recipients with no clinical history of COVID-19 and no active graft-vs-host disease more than 3 months after transplant. Vaccination was performed in our department between January 20 and April 17, 2021. All participants provided written informed consent, and the study was approved by Nantes University Hospital review board. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

    Previous asymptomatic COVID-19 infection was investigated before the first vaccine injection by testing for antinucleocapsid antibodies (anti–SARS-CoV-2 immunoassay; Roche Elecsys). Antibody responses to the SARS-CoV-2 spike protein receptor–binding domain (Elecsys anti–SARS-CoV-2-S) were tested twice, at the time of the second injection and approximately 1 month after the second injection. As recommended by the manufacturer, titers greater than or equal to 0.8 U/mL were considered positive, with the highest value being greater than 250 U/mL. Associations between clinical characteristics and antibody responses were investigated using 1-sided χ2 and Wilcoxon tests with R statistical software version 4.0.2 (R Project for Statistical Computing) via BiostaTGV. P < .05 was considered significant.

    Results

    Previous asymptomatic SARS-CoV-2 infection was documented in 4 of 121 enrolled patients, who were, therefore, excluded from the study. They were vaccinated twice, and all reached specific IgG titers greater than 250 U/mL after the second dose. Characteristics of the 117 allogeneic HSCT recipients retained (median [range] age, 57 [20-75] years; 70 men [60%]) are provided in the Table. The median (range) interval between the first and the second dose was 22 (16-37) days. At the time of the second injection, 63 patients (54%) had a positive anti-spike antibody response. The median IgG titer for responders was 15.8 U/mL and ranged from 0.9 U/mL to more than 250 U/mL, with the latter occurring in 4 patients (3%). The second antibody testing was performed at a median (range) interval of 35 (18-77) days after the second dose and was positive in 97 patients (83%), with IgG titers ranging from 0.9 U/mL to greater than 250 U/mL; 72 (62%) patients reached the highest IgG titer. Factors associated with the absence of response were a haplotransplant, recent (<1 year) HSCT (Figure), lymphopenia (<1000 cells/μL; to convert lymphocyte count to cells × 109/L, multiply by 0.001), and receipt of immunosuppressive treatment or chemotherapy at the time of vaccination (Table).

    Patients were requested to answer questionnaires for 7 days following dose 1 and dose 2. The responses showed that the 2 vaccine injections were very safe. Only grade 1 or 2 adverse reactions occurred in 51 of 106 patients (48%) after dose 1 and 34 of 87 patients (39%) after dose 2. These rates were comparable to those for a healthy vaccinated population of 25 caregivers from the hematology department of Nantes University Hospital, who all achieved the highest IgG titer after the second dose. Finally, at a median (range) follow-up of 58 (39-98) days, no COVID-19 infection was documented.

    Discussion

    Despite the limitations inherent to an observational analysis and the fact that the cohort was small and from a single center, this study found a high response rate of 83% in this cohort of allogeneic HSCT recipients after 2 doses of BNT162b2 vaccine. Of note, 62% of the patients achieved the highest IgG titer also reached by a concomitant healthy cohort. This is much more than the 54% rate of seroconversion that has been reported after 2 doses in solid-organ transplant recipients5 and compares favorably with data obtained in patients treated for solid tumors, for whom a 95% of response rate was obtained after the second dose.6 This humoral response is, however, only 1 marker of immunity, and allogeneic HSCT recipients will likely have differences in T cell reactivity that should be explored.

    Back to top
    Article Information

    Accepted for Publication: July 19, 2021.

    Published: September 14, 2021. doi:10.1001/jamanetworkopen.2021.26344

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Le Bourgeois A et al. JAMA Network Open.

    Corresponding Author: Patrice Chevallier, MD, PhD, Hematology Department, Nantes University Hospital, Centre Hospitalo-Universitaire Hotel-Dieu, Place A Ricordeau, 44093 Nantes Cedex, France (patrice.chevallier@chu-nantes.fr).

    Author Contributions: Drs Le Bourgeois and Chevallier had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Le Bourgeois, Guillaume, Chevallier.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Guillaume, Chevallier.

    Critical revision of the manuscript for important intellectual content: All authors.

    Statistical analysis: Béné, Chevallier.

    Administrative, technical, or material support: Coste-Burel, Guillaume, Garnier, Chevallier.

    Supervision: Le Bourgeois, Béné.

    Conflict of Interest Disclosures: Dr Chevallier reported receiving honoraria from Pfizer outside the submitted work. No other disclosures were reported.

    Additional Contributions: We thank the paramedical staff of the Hematology Department and of the Virology Department, Nantes University Hospital, for their assistance. Berthe-Marie Imbert, PharmD, PhD, Thomas Drumel, PharmD, Beatrice Mahé, MD, Viviane Dubruille, MD, Nicolas Blin, MD, Anne Lok, MD, Cyrille Touzeau, MD, PhD, Thomas Gastinne, MD, Maxime Jullien, MD, Sophie Vanthygem, MD, Philippe Moreau, MD, and Steven Le Gouill, MD, PhD (all from Nantes University Hospital), provided data and commented on the manuscript. Patricia Lespart, Nursing Diploma, Ghislaine Francois, Nursing Diploma, and Katia Godart, Nursing Diploma (all from the Hematology Department, Nantes University Hospital) administered vaccines and helped collect samples and questionnaires. None of these individuals was compensated beyond their normal salaries.

    References
    1.
    García-Suárez  J, de la Cruz  J, Cedillo  Á,  et al; Asociación Madrileña de Hematología y Hemoterapia (AMHH).  Impact of hematologic malignancy and type of cancer therapy on COVID-19 severity and mortality: lessons from a large population-based registry study.   J Hematol Oncol. 2020;13(1):133. doi:10.1186/s13045-020-00970-7PubMedGoogle ScholarCrossref
    2.
    Xhaard  A, Xhaard  C, D’Aveni  M,  et al.  Risk factors for a severe form of COVID-19 after allogeneic haematopoietic stem cell transplantation: a Société Francophone de Greffe de Moelle et de Thérapie cellulaire (SFGM-TC) multicentre cohort study.   Br J Haematol. 2021;192(5):e121-e124. doi:10.1111/bjh.17260PubMedGoogle ScholarCrossref
    3.
    Walsh  EE, Frenck  RW  Jr, Falsey  AR,  et al.  Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates.   N Engl J Med. 2020;383(25):2439-2450. doi:10.1056/NEJMoa2027906PubMedGoogle ScholarCrossref
    4.
    Chevallier  P, Coste-Burel  M, Le Bourgeois  A,  et al  Safety and immunogenicity of a first dose of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem-cells recipients.   EJHaem. Published online June 1, 2021. doi:10.1002/jha2.242PubMedGoogle Scholar
    5.
    Boyarsky  BJ, Werbel  WA, Avery  RK,  et al.  Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients.   JAMA. 2021;325(21):2204-2206. doi:10.1001/jama.2021.7489PubMedGoogle ScholarCrossref
    6.
    Barrière  J, Chamorey  E, Adjtoutah  Z,  et al.  Impaired immunogenicity of BNT162b2 anti-SARS-CoV-2 vaccine in patients treated for solid tumors.   Ann Oncol. 2021;32(8):1053-1055. doi:10.1016/j.annonc.2021.04.019PubMedGoogle ScholarCrossref
    ×