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A phase II randomized, placebo-controlled, multicenter trial to evaluate the efficacy of cytomegalovirus PepVax vaccine in preventing cytomegalovirus reactivation and disease after allogeneic hematopoietic stem cell transplant
Nakamura, R., La Rosa, C., Yang, D., Hill, J. A., Rashidi, A., Choe, H., Zhou, Q., Lingaraju, C. R., Kaltcheva, T., Longmate, J., et al
Haematologica. 2024
Abstract
Not available.
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2.
Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients
Amarin, J. Z., Dulek, D. E., Simmons, J., Hayek, H., Chappell, J. D., Nochowicz, C. H., Kitko, C. L., Schuster, J. E., Muñoz, F. M., Bocchini, C. E., et al
Blood advances. 2024
Abstract
Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B and T cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells (PBMCs) collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over three influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and pre- to post-vaccination geometric mean fold-rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination-inhibition antibody titers (28-42 days and approximately 6 months after two doses). For cell subpopulations identified as predictive of a response to all three antigens, we conducted a sensitivity analysis including time post-transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations. Seven significantly predicted responses to all three antigens 28-42 days after a two-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of post-transplant vaccine administration. In conclusion, several B and T cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.
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3.
Real-world challenges in eligibility for MMR vaccination two years after autologous and allogeneic HSCT
Punchhi, G., Negus, R., Saif, H., Pritchard, S., Owen, O., Sehmbi, A., Hamm, C.
Vaccine. 2023
Abstract
Measles outbreaks have raised concerns of fatal infections in immunocompromised patients. Canadian guidelines advise administration of live vaccines, such as measles, mumps, and rubella (MMR), two yearsafter hematopoietic stem cell transplant (HSCT) yet studies have not assessed eligibility based on medication contraindications. We retrospectively reviewed the charts of 72 autologous (auto-HSCT) and 68 allogeneic (allo-HSCT) recipients at the Windsor Regional Cancer Center to determine MMR reactivity and eligibility based on administration of contraindicated medications two years post-HSCT. Reactivity to measles, mumps, and rubella in auto-HSCT recipients was 49.1 %, 28.8 %, and 52.3 %, respectively, and in allo-HSCT recipients was 75.6 %, 57.8 %, and 64.4 %, respectively. Immunity to all three components was significantly different between transplant types (p = 0.0002). Nearly 80 % of auto-HSCT patients were on a contraindicated medication at two years compared to 45 % of allo-HSCT recipients. Auto-HSCT recipients require MMR revaccination, but it is contraindicated in a large proportion of patients.
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4.
Third BNT162b2 mRNA SARS-CoV-2 Vaccine Dose Significantly Enhances Immunogenicity in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation
Henig, I., Isenberg, J., Yehudai-Ofir, D., Leiba, R., Ringelstein-Harlev, S., Ram, R., Avni, B., Amit, O., Grisariu, S., Azoulay, T., et al
Vaccines. 2023;11(4)
Abstract
COVID-19-related mortality among hematopoietic stem cell transplantation (HSCT) recipients in the pre-vaccine era ranged between 22 and 33%. The Pfizer/BioNTech BNT162b2 vaccine demonstrated significant immunogenicity and efficacy in the healthy population; however, its long-term effects on allogeneic HSCT recipients remained unclear. Our study longitudinally evaluated humoral and cellular responses to the BNT162b2 vaccine in adult allogeneic HSCT patients. A positive response was defined as antibody titers ≥ 150 AU/mL post-second vaccination. Among 77 included patients, 51 (66.2%) responded to vaccination. Response-associated factors were female gender, recent anti-CD20 therapy, and a longer interval between transplant and vaccination. Response rates reached 83.7% in patients vaccinated >12 months post-transplant. At 6 months post-second vaccination, antibody titers dropped, but were significantly increased with the booster dose. Moreover, 43% (6/14) of non-responders to the second vaccination acquired sufficient antibody titers after booster administration, resulting in an overall response rate of 79.5% for the entire cohort. The BNT162b2 vaccine was effective in allogeneic transplant recipients. Although antibody titers decreased with time, the third vaccination led to their significant elevation, with 93% of third-dose responders maintaining titers above 150 AU/mL at 3 months post-administration.
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5.
Long-term immunity against tetanus and diphtheria after vaccination of allogeneic stem cell transplant recipients
Einarsdottir, S., Sverrisdottir, I., Vaht, K., Bergström, T., Brune, M., Andersson, P. O., Wenneras, C., Ljungman, P.
Transplantation and cellular therapy. 2023
Abstract
BACKGROUND Revaccination against tetanus and diphtheria after allogeneic hematopoietic stem cell transplant (HCT) is usually effective, but the duration of the immunity is unknown. OBJECTIVE To study humoral immunity to tetanus and diphtheria in long-term survivors and to provide knowledge regarding the need for boosters. STUDY DESIGN The median time from transplantation to blood sampling was 14 years (min-max: 8-40). All patients had received at least 3 doses of vaccines, against both tetanus and diphtheria, either monovalent or combination vaccines containing a full dose of the diphtheria toxoid component (D). In addition, one or more booster doses were administered to 21/146 (14 %) of the patients. Enzyme-linked immunosorbent assays (ELISA) were used where levels below <0.1 IU/mL for diphtheria and <0.01 IU/mL for tetanus were considered "low" or "seronegative". Values between 0.01-0.5 IU/mL for tetanus and 0.1-1.0 IU/mL for diphtheria were considered to represent "partial protection" and levels above 0.5 and 1.0 IU/mL, respectively were considered "high" and protective. RESULTS In all, 39% were seronegative against diphtheria, 52% had "some protection" and 9% had a high titer. In contrast, no patient had become seronegative to tetanus, 32% had "partial protection" against tetanus and 68% had a high titer. In multivariate analysis active Graft-versus-host-disease (GvHD), gender or time from sampling did not affect the probability of becoming seronegative or seropositive. Younger age was associated with lower antibody levels to tetanus toxoid, but age was not correlated with antibody levels against diphtheria toxoid. CONCLUSION Tetanus immunity was maintained after vaccination in most long-term survivors, but immunity against diphtheria was poor and boosters should be considered.
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6.
A phase 3 randomized, double-blind, comparator-controlled study to evaluate safety, tolerability and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in allogeneic hematopoietic cell transplant recipients (PNEU-STEM)
Wilck, M., Cornely, O. A., Cordonnier, C., Velez, J. D., Ljungman, P., Maertens, J., Selleslag, D., Mullane, K. M., Nabhan, S., Chen, Q., et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
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Editor's Choice
Abstract
BACKGROUND Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk for pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE™), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients. METHODS Participants received 3 doses of V114 or PCV13 in one-month intervals starting 3-6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAXTM 23 or a fourth dose of PCV (if they experienced chronic graft versus host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group. RESULTS A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90. CONCLUSIONS V114 was well tolerated in allo-HCT recipients with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and higher for V114 serotypes 22F and 33F. Study results support use of V114 in allo-HCT recipients.
PICO Summary
Population
Adults and children who received allo-HCT 90 to 180 days prior to randomization, from 44 centres in 10 countries (n=274)
Intervention
3 doses of V114 pneumococcal conjugate vaccine in one-month intervals starting 3-6 months after transplant. For people who experienced chronic GvHD, a fourth dose of PNEUMOVAXTM 23 was given (n=139)
Comparison
Three doses of PCV13 in pneumococcal conjugate vaccine in one-month intervals starting 3-6 months after transplant. For people who experienced chronic GvHD, a fourth dose was given. (n=135)
Outcome
The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at Day 90.
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7.
Neutropenia Secondary to SARS-Cov2 Vaccination in Post-Hematopoietic Stem Cell Transplant (HSCT) Patients
Juárez-Salcedo, L. M., Feijóo Monroy, S., García-Herce, C., Alonso, A., Aguado, B., Ortiz, J., Figuera, A., Cámara, J. R.
Mediterranean journal of hematology and infectious diseases. 2023;15(1):e2023014
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8.
Antibody response after third dose of COVID-19 mRNA vaccination in allogeneic hematopoietic stem cell transplant recipients is comparable to that in healthy counterparts
Takagi, E., Terakura, S., Fujigaki, H., Okamoto, A., Miyao, K., Sawa, M., Morishita, T., Goto, T., Ozawa, Y., Nishida, T., et al
International journal of hematology. 2023
Abstract
To determine the efficacy of SARS-CoV-2 mRNA vaccination for allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, we measured antibody titer serially in 92 allo-HSCT patients. Among the evaluable 87 patients, median age at vaccination was 53 years (range, 18-75). The average time between allo-HSCT and vaccination was 3.3 years (range, 0.5-15.7). One month after the second dose, 70 patients (80.5%) had a positive response, whereas 17 patients (19.5%) had a negative response (< 20 U/mL). Only patients older than 44 years had a negative response. Low IgM level was the only significant predictor of vaccine failure in elderly patients. When antibody response before and after the third vaccination was examined in 47 patients, antibodies increased significantly from a median of 18.3 U/mL to 312.6 U/mL (P < 0.01). The median antibody titer after the third vaccination of healthy individuals (n = 203) was 426.4 U/mL, which was comparable to that of patients (P = 0.2). The antibody titer after the third mRNA vaccination increased even in patients whose first two mRNA vaccinations failed. These findings suggest that allo-HSCT recipients should receive the mRNA vaccine regularly.
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Impact of a third dose of anti-SARS-CoV-2 vaccine in hematopoietic cell transplant recipients: A Japanese multicenter observational study
Mori, Y., Uchida, N., Wake, A., Miyawaki, K., Eto, T., Nakamura, T., Iwasaki, H., Ito, Y., Tanimoto, K., Katayama, Y., et al
Vaccine. 2023
Abstract
This prospective observational study aimed to assess the serological response and safety after the third booster shot of SARS-CoV-2 mRNA vaccines in 292 hematopoietic cell transplant (HCT) recipients. In our patients, mild systemic reactions were present in 10-40% and GVHD aggravation in 1.1%. Overall, clinically relevant response (>250 U/mL) was observed in 93.1% of allogeneic (allo)-HCT recipients and 70.6% of autologous (auto)-HCT recipients, respectively. Of note, detectable antibody response with any titer following the first two doses was a powerful predictor for adequate response after booster shot in both cohorts. For such patients, 98.8% of allo- and 92.3% of auto-HCT recipients obtained clinically relevant response after dose 3. In addition, continued systemic steroid and/or calcineurin inhibitors at the booster shot significantly correlated with serological response. These findings highlighted that booster vaccination efficiently improved serological response without safety concerns and thus recommended for the majority of HCT recipients.
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10.
Vaccine response after pneumococcal vaccination in allogeneic hematopoietic stem cell transplant recipients
Cheplowitz, H., Patel, N., Kim, A., Logan, C., Law, N., Koura, D., Haste, N., Medley, K., Trinh, J., Sanders, T., et al
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2023;:10781552231165733
Abstract
Current guidelines for vaccination in allogeneic hematopoietic stem cell transplant (HCT) recipients recommend initiation of pneumococcal vaccination series three to six months post-HCT, with most data supporting initiation at six months due to a more robust immune response. This single-center, retrospective, observational chart review aimed to evaluate the impact of initiating the pneumococcal vaccine series at three months post-HCT compared to six months post-HCT. The primary endpoints were defined as a percentage of patients with a serologic response of >1 and >1.3 µg/mL for over 50% of the defined serotypes. Outcomes showed no difference in immunologic response between the two groups.