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1.
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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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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A Retrospective Review of Revaccination Patterns in Pediatric Hematopoietic Stem Cell Transplantation Recipients
Wohlschlaeger, A., Levy, E., Khan, R. N., Heimall, J., Fisher, B. T., Metjian, T. A., Elgarten, C. W., Freedman, J. L.
Journal of pediatric hematology/oncology nursing. 2023;:27527530221147861
Abstract
Background: After a hematopoietic stem cell transplantation (HSCT), patients are left with little to no immunity to prevent infections. Importantly, this includes immunity gained from previous exposures, including vaccinations. This loss of immunity is a direct result of previous chemotherapy, radiation, and conditioning regimens the patients receive. It is critical to revaccinate patients post-HSCT to ensure protective immunity against vaccine-preventable diseases. Before 2017, all patients at our institution were referred to their pediatrician at approximately 12-month post-HSCT to be revaccinated. Clinical concern was raised at our institution regarding nonadherence and errors in vaccine schedules. Methods: To understand the magnitude of the problem with revaccination, we performed an internal audit of post-vaccine adherence in patients who received an HSCT between 2015 and 2017. A multidisciplinary team was developed to review the audit results and make recommendations. Results: This audit revealed delays in the initiation of the vaccine schedule, incomplete adherence to the recommended revaccination schedule, and errors in administration. Discussion: Based on the review of the data, the multidisciplinary team recommended an approach for systematic assessment of vaccine readiness and centralization of the administration of vaccines to be done within the stem cell transplant outpatient center.
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4.
COVID-19 mRNA Vaccine Tolerance and Immunogenicity in Hematopoietic Stem Cell Transplantation Recipients Aged 5-11 Years Old-Non-Randomized Clinical Trial
Matkowska-Kocjan, A., Owoc-Lempach, J., Ludwikowska, K., Szenborn, F., Moskwa, N., Kurek, K., Kałwak, K., Szenborn, L., Ussowicz, M.
Vaccines. 2023;11(1)
Abstract
The SARS-CoV-2 pandemic had a devastating impact on the world's population in the years 2020-2022. The rapid development of vaccines enabled a reduction in the mortality and morbidity of COVID-19, but there are limited data about their effects on immunocompromised children. The aim of this prospective study was to evaluate the safety and efficacy of the mRNA BNT162b2 (Pfizer/Biontech) vaccine in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. MATERIAL AND METHODS Two cohorts of 34 children after allo-HSCT and 35 healthy children aged 5-11 years were vaccinated with two doses of the mRNA BNT162b2 (10 µg) vaccine. All children were evaluated for adverse effects with electronic surveys and the immunogenicity of the vaccine was assessed with anti-SARS-CoV-2 IgG titer measurements. RESULTS All reported adverse events (AEs) were classified as mild. The most common AE was pain at the injection site. All the other AEs (both local and systemic) were rarely reported (<15% patients). Both groups showed a similar response in anti-SARS-CoV-2 IgG production. Patients after allo-HSCT that were undergoing immunosuppressive treatment presented a poorer immunological response than patients off of treatment. Time since HSCT, patient age, lymphocyte count, and total IgG concentration did not correlate with initial/post-vaccination anti-SARS-CoV-2 IgG titers. Most patients who were eligible for a third dose of the vaccine had an excellent humoral response observed after two vaccine doses. CONCLUSIONS The COVID-19 mRNA BNT162b2 vaccine is very well tolerated and highly immunogenic in 5-11-year-old children after HSCT. Children >2 years of age after HSCT who did not receive immunosuppressive treatment presented excellent antibody production after two doses of the vaccine, but children on immunosuppression may require a more intense vaccination schedule.
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5.
Measles, mumps, and rubella revaccination in children after completion of chemotherapy and hematopoietic stem cell transplantation: a single-center prospective efficacy and safety analysis
Wang, M., Yuan, Q., Deng, P. F., Fei, Y., Zhang, H., Zhou, F., Chen, W. J., Cao, Q., Chen, J., Gao, Y. J.
World journal of pediatrics : WJP. 2023
Abstract
BACKGROUND Chemotherapy and hematopoietic stem cell transplantation (HSCT) can damage the immune system, and may result in a loss of protection from infectious diseases. This study aimed to evaluate the impact of these treatments on the decrease in antibody titers of the measles, mumps, and rubella (MMR) vaccine and seroconversion post-revaccination of MMR. METHODS After completion of treatment for primary diseases, participants received an MMR revaccination. Antibody titers for MMR before revaccination were analyzed for all 110 children. After revaccination, 68 participants received a follow-up evaluation of antibody titer and adverse reaction. RESULTS Multivariable analysis showed that therapeutic schedules were the only factor correlated with lack of antibody titers for measles after completing treatment (P = 0.008), while for mumps and rubella, no statistically significant difference was observed. Importantly, our study clearly demonstrated positive seroconversion rates for measles (97.5%), mumps (81.0%), and rubella (93.2%), with antibody levels rising across the board and peaking at around 6 months following revaccination. However, 6 months after revaccination, a downtrend of antibody titer levels was observed, which is comparatively earlier than the waning immunity observed in healthy children. Furthermore, we found MMR revaccination to be safe, with only a single adverse reaction (local pain at the injection site) reported. CONCLUSIONS MMR revaccination is immunogenic for the population. We suggest periodic monitoring of antibody titers, in addition to a booster vaccination, although the optimal timing of booster vaccination remains to be investigated further.
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6.
The Durability of Antibody Responses of Two Doses of High-Dose Relative to Two Doses of Standard-Dose Inactivated Influenza Vaccine in Pediatric Hematopoietic Cell Transplant Recipients: A Multi-Center Randomized Controlled Trial
Schuster, J. E., Hamdan, L., Dulek, D. E., Kitko, C. L., Batarseh, E., Haddadin, Z., Stewart, L. S., Stahl, A., Potter, M., Rahman, H., et al
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2023
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Abstract
BACKGROUND Our previous study established a 2-dose regimen of high-dose trivalent influenza vaccine (HD-TIV) to be immunogenically superior compared to a 2-dose regimen of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric allogeneic hematopoietic cell transplant (HCT) recipients. However, the durability of immunogenicity and the role of time post-HCT at immunization as an effect modifier are unknown. METHODS This phase II, multi-center, double-blinded, randomized controlled trial compared HD-TIV to SD-QIV in children 3-17 years old who were 3-35 months post-allogeneic HCT, with each formulation administered twice, 28-42 days apart. Hemagglutination inhibition (HAI) titers were measured at baseline, 28-42 days following each dose, and 138-222 days after the second dose. Using linear mixed effects models, we estimated adjusted geometric mean HAI titer ratios (aGMR: HD-TIV/SD-QIV) to influenza antigens. Early and late periods were defined as 3-5 and 6-35 months post-HCT, respectively. RESULTS During 3 influenza seasons (2016-2019), 170 participants were randomized to receive HD-TIV (n = 85) or SD-QIV (n = 85). HAI titers maintained significant elevations above baseline for both vaccine formulations, although the relative immunogenic benefit of HD-TIV to SD-QIV waned during the study. A 2-dose series of HD-TIV administered late post-HCT was associated with higher GMTs compared to the early post-HCT period (late group: A/H1N1 aGMR = 2.16, 95% confidence interval [CI] = [1.14-4.08]; A/H3N2 aGMR = 3.20, 95% CI = [1.60-6.39]; B/Victoria aGMR = 1.91, 95% CI = [1.01-3.60]; early group: A/H1N1 aGMR = 1.03, 95% CI = [0.59-1.80]; A/H3N2 aGMR = 1.23, 95% CI = [0.68-2.25]; B/Victoria aGMR = 1.06, 95% CI = [0.56-2.03]). CONCLUSIONS Two doses of HD-TIV were more immunogenic than SD-QIV, especially when administered ≥6 months post-HCT. Both groups maintained higher titers compared to baseline throughout the season. CLINICAL TRIALS REGISTRATION NCT02860039.
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7.
Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants
Schuster, J. E., Hamdan, L., Dulek, D. E., Kitko, C. L., Batarseh, E., Haddadin, Z., Stewart, L. S., Stahl, A., Potter, M., Rahman, H., et al
The New England journal of medicine. 2023
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Vaccine Adherence and Postvaccination Serological Status of Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience
Ozboru Askan, O., Ozden, T. A., Karasu Tezcan, G., Keskindemirci, G., Bakir, A., Tugcu, D., Pekun, F., Yesilipek, A., Gokcay, E. G.
Journal of pediatric hematology/oncology. 2022
Abstract
Despite developing consensus guidelines addressing immunization after hematopoietic stem cell transplantation (HSCT), studies showed deviations from recommended immunization practices commonly occur. Difference between the ideal scenario presented in guidelines and real-life scenarios is one of the most recognized barriers to implementing recommended practices. Therefore, this study aimed to evaluate pediatric allogeneic HSCT recipients' adherence to revaccination schedule and evaluate the serological status after immunization. Transplant and vaccination records of children who were followed up at least 2 years after HSCT, postvaccination antibody results of vaccine-preventable diseases were evaluated retrospectively. Total of 173 patients have enrolled in this study. Median revaccination onset time was post-transplant 15 months. Adherence to revaccination program was 30% for inactive and 11.4% for live vaccines. Oral polio vaccine was given to 22 patients, and Bacille-Calmette-Guerin vaccine was applied to 3. Seropositivity after revaccination was >90% for Hepatitis B, Hepatitis A, pertussis, and measles, and it was 88.5% for rubella, 80% for mumps and varicella. Measles seropositivity was low in children with hemoglobinopathy. In subgroup assessments of pertussis, patients vaccinated with low antigen-containing pertussis vaccine (Tdap) had higher seropositivity of adenylate cyclase toxin. Our findings revealed the importance of careful monitoring of current practices in pediatric HSCT recipients.
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Shorter duration of protection and lower geometric mean titers against A/H3N2 antigen of the quadrivalent influenza vaccine in children post-allogeneic hematopoietic stem cell transplantation
Kang, K. R., Kim, Y. J., Ahn, M. B., Kang, H. M., Kim, S. K., Lee, J. W., Chung, N. G., Cho, B., Jeong, D. C., Kang, J. H.
Bone marrow transplantation. 2022;:1-3
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10.
The Effect of Early BCG-Vaccination of SCID Pediatric Patients on the Outcome of Hematopoietic Stem Cell Transplantation Using Reduced Conditioning Regimen
Hamidieh, A. A., Jafari, L., Behfar, M., Karamlou, Y., Shamsipour, M., Mohseni, R., Farajifard, H., Salajegheh, P.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND The eminence of Bacillus Calmette-Guerin (BCG) vaccine in the vaccination program of newborns, especially in low-income developing countries where tuberculosis is prevalent, has been conspicuous throughout the years; however, the application of the aforementioned vaccine is not without constraints, especially in patients afflicted with immunodeficiency diseases, such as Severe Combined Immunodeficiency (SCID). OBJECTIVE The desideratum of this study is to evaluate whether or not the administration of BCG vaccine upon birth could attenuate the success of hematopoietic stem cell transplantation (HSCT) in SCID pediatric patients STUDY DESIGN In the current study, 30 SCID patients who underwent HSCT using reduced intensity conditioning regimen (RIC) were followed-up for 2 years post-HSCT. The outcome of HSCT was evaluated in both non-BCG-vaccinated (12 patients) and BCG-vaccinated (18 patients) groups. RESULTS Our results demonstrated that patients who had been BCG vaccinated displayed higher incidences of acute GvHD (aGvHD); however, the incidence of chronic GvHD did not differ between the two groups. The overall survival (OS) rate in patients who received the BCG vaccine was similar than their non-vaccinated counterparts. We speculate that the reason that BCG-vaccinated individuals' survival rate, despite having the risk factor of being BGC-vaccinated, was similar to the non-BCG-vaccinated group was due to the fact that they received RIC as their conditioning regimen. CONCLUSION The result of our study indicated that early BCG vaccination was associated with a higher risk of aGVHD. Additionally, the OS of BCG-vaccinated patients was similar in comparison to their non-vaccinated counterparts; alluding to the possibility that the same RIC regimen might be the reason for such outcome, since no other variation between the two groups existed. Regarding to the BCG vaccine affect the outcome of HSCT, we suggest that the administration of BCG vaccine should be deferred until three months of age so that apt testing, without the interference of maternal antibodies, could be performed; however, it is noteworthy that this study could benefit from a bigger cohort in order to further validate the outcome, as the possible reason for some factors not becoming statistically significant was the small sample size of this study.