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1.
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.
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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6.
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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7.
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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8.
Impact of a booster dose on SARS-CoV2 mRNA vaccine-specific humoral-, B- and T cell immunity in pediatric stem cell transplant recipients
Thole, L. M. L., Tóth, L., Proß, V., Siegle, J., Stahl, C., Hermsdorf, G., Knabe, A., Winkler, A., Schrezenmeier, E., Ludwig, C., et al
Frontiers in immunology. 2023;14:1239519
Abstract
Stem cell transplant recipients (SCTR) are imperiled to increased risks after SARS-CoV2 infection, supporting the need for effective vaccination strategies for this vulnerable group. With respect to pediatric patients, data on immunogenicity of SARS-CoV2 mRNA-based vaccination is limited. We therefore comprehensively examined specific humoral, B- and T cell responses in a cohort of 2-19 year old SCTR after the second and third vaccine dose. Only after booster vaccination, transplant recipients reached similar levels of vaccine-specific IgG, IgA and neutralizing antibodies against omicron variant as age-matched controls. Although frequencies of SARS-CoV2 specific B cells increased after the third dose, they were still fourfold reduced in patients compared to controls. Overall, the majority of individuals enrolled mounted SARS-CoV2 Spike protein-specific CD4(+) T helper cell responses with patients showing significantly higher portions than controls after the third dose. With respect to functionality, however, SCTR were characterized by reduced frequencies of specific interferon gamma producing CD4(+) T cells, along with an increase in IL-2 producers. In summary, our data identify distinct quantitative and qualitative impairments within the SARS-CoV2 vaccination specific B- and CD4(+) T cell compartments. More importantly, humoral analyses highlight the need for a booster vaccination of SCTR particularly for development of neutralizing antibodies.
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9.
Cost-Effectiveness Analysis of Vaccination With Recombinant Zoster Vaccine Among Hematopoietic Cell Transplant Recipients and Persons With Other Immunocompromising Conditions Aged 19 to 49 Years
Leidner, A. J., Anderson, T. C., Hong, K., Ortega-Sanchez, I. R., Guo, A., Pike, J., Prosser, L. A., Dooling, K. L.
Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research. 2023;26(2):204-215
Abstract
OBJECTIVES This study aimed to estimate the cost-effectiveness of the use of recombinant zoster vaccine (RZV) (Shingrix), which protects against herpes zoster (HZ), among immunocompromised adults aged 19 to 49 years, as a contribution to deliberations of the Advisory Committee on Immunization Practices. METHODS Hematopoietic cell transplant (HCT) recipients experience a high incidence of HZ, and the efficacy of RZV in preventing HZ has been studied in clinical trials. The cost-effectiveness model calculated incremental cost-effectiveness ratios that compared vaccination with RZV with a no vaccination strategy among adults aged 19 to 49 years. Costs and outcomes were calculated until age 50 years using the healthcare sector perspective and summarized as cost per quality-adjusted life-year (QALY) gained. The base case represents HCT recipients, with scenario analyses representing persons with other immunocompromising conditions, including hematologic malignancies, human immunodeficiency virus, and autoimmune and inflammatory conditions. Uncertainty was investigated using univariate, multivariate, and probabilistic sensitivity analyses. RESULTS Base-case results indicated vaccination with RZV would avert approximately 35% of HZ episodes and complications, while saving approximately 11% of net costs. Compared with no vaccination, vaccination of HCT recipients with RZV generated cost-savings (ie, lower costs and improved health) in the base case and in 81% of simulations in the probabilistic analysis. In scenario analyses, vaccination cost US dollar ($) 9500/QALY among patients with hematologic malignancies, $79 000/QALY among persons living with human immunodeficiency virus, and $208 000/QALY among persons with selected autoimmune and inflammatory conditions. CONCLUSIONS Generally favorable economic estimates supported recommendations for vaccination of immunocompromised adults with RZV to prevent episodes of HZ and related complications.
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10.
Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation
Randi, B. A., Fernandes, E. G., Higashino, H. R., Lopes, M. H., Rocha, V. G., Costa, S. F., Sartori, A. M. C.
Revista do Instituto de Medicina Tropical de Sao Paulo. 2023;65:e21
Abstract
The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.