Revaccination and Its Efficacy Against Hepatitis B Virus, Measles, Mumps, and Rubella in Children After Allogeneic Hematopoietic Stem Cell Transplantation

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Revaccination and Its Efficacy Against Hepatitis B Virus, Measles, Mumps, and Rubella in Children After Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a critical therapeutic intervention for pediatric patients with malignant hematological diseases, non-malignant hematological disorders, immunodeficiency syndromes, and metabolic conditions. While this procedure can be life-saving, the prolonged immunodeficiency before complete immune reconstitution post-transplant increases susceptibility to infections. Revaccination is essential to restore protective immunity against vaccine-preventable diseases. This study evaluates the efficacy and safety of revaccination against hepatitis B virus (HBV), measles, mumps, and rubella (MMR) in children following allo-HSCT, focusing on antibody seroreversion risk factors and immune response outcomes.

Post-Transplant Immune Reconstitution and Vaccination Guidelines

Immune recovery after allo-HSCT occurs gradually: CD8+ T lymphocytes reconstitute within 6 months, CD4+ T lymphocytes within 12 months, and B lymphocytes within 12–24 months. Graft-versus-host disease (GVHD) further delays immune recovery. Current guidelines recommend inactivated vaccines starting 6–12 months post-transplant, provided patients are off immunosuppressants for ≥3 months, have no active GVHD, and have normal lymphocyte counts and immunoglobulin levels. Live-attenuated vaccines, such as MMR, require stricter criteria: administration ≥24 months post-transplant, ≥1 year after immunosuppressant cessation, ≥8 months post-intravenous immunoglobulin (IVIG), and no active GVHD.

Study Cohort and Methodology

A retrospective analysis included 516 pediatric allo-HSCT recipients evaluated at Shanghai Children’s Medical Center (SCMC) between 2017 and 2023. Eligibility criteria included remission >6 months post-transplant, immunosuppressant discontinuation ≥3 months, absence of active GVHD, normal T-cell subsets, and immunoglobulin levels. Exclusions involved severe prior vaccine reactions or allergies. Median age at transplantation was 4.8 years (interquartile range [IQR]: 2.2–9.2 years), with 63.8% male participants. Aplastic anemia (37.6%) was the most common primary diagnosis, and peripheral blood stem cells were used in 89.7% of cases.

Hepatitis B Surface Antibody (HBsAb) Seroreversion and Revaccination

Pre-transplant HBsAb positivity was observed in 81.0% (418/516) of patients, but post-transplant assessment revealed only 15.5% (80/516) remained positive. Among those initially HBsAb-positive, 18.9% (79/417) retained positivity post-transplant. The median time to vaccination assessment was significantly shorter in the HBsAb-positive group (1.9 years [IQR: 1.3–2.3]) compared to the seroreversion group (2.2 years [IQR: 1.9–2.8]; P <0.001). Multivariate analysis identified three independent factors influencing HBsAb seroreversion:

  1. Pre-transplant HBsAb titer: High titers (≥1000 U/L) pre-transplant reduced seroreversion risk (OR: 0.15; 95% CI: 0.06–0.36; P <0.001).
  2. Completion of three-dose HBV vaccination pre-transplant: This lowered seroreversion risk (OR: 0.38; 95% CI: 0.15–0.83; P = 0.023).
  3. Time post-transplant: Assessments ≥2 years post-transplant increased seroreversion likelihood (OR: 3.49; 95% CI: 2.11–5.88; P <0.001).

Revaccination with three HBV doses in 40 initially seronegative patients resulted in a 97.5% (39/40) seroconversion rate one month post-completion, demonstrating robust immunogenicity.

Measles, Mumps, and Rubella Antibody Response

Pre-transplant MMR vaccination coverage was 65.7% (339/516), but only 62 patients underwent pre-revaccination antibody testing. Positive rates for measles, mumps, and rubella antibodies were 19.4% (12/62), 14.5% (9/62), and 17.7% (11/62), respectively. Post-revaccination, 29 children were monitored for immune responses:

  • Measles: 96.6% (28/29) seroconverted.
  • Mumps: 69.0% (20/29) seroconverted.
  • Rubella: 88.5% (23/26) seroconverted.

No significant associations were found between MMR seroreversion and factors like gender, malignancy status, or time post-transplant.

Safety Profile of Revaccination

Among 464 revaccinated children, 6.5% (30/464) experienced adverse events, primarily mild fever (2.6%, 12/464) resolving with symptomatic care. No severe reactions or vaccine-related complications were reported, underscoring the safety of post-transplant revaccination.

Clinical Implications and Recommendations

This study highlights the critical decline in vaccine-induced immunity post-allo-HSCT, particularly for HBV, with seropositivity dropping from 81% to 15.5%. The strong correlation between pre-transplant HBV vaccination completeness and reduced seroreversion emphasizes the importance of robust pre-transplant immunization. For live-attenuated vaccines like MMR, delayed administration until ≥24 months post-transplant ensures safer and more effective responses.

The findings advocate for structured revaccination protocols integrating serological monitoring to guide timing and necessity. For HBV, revaccination at ≥1 year post-transplant (off immunosuppressants ≥3 months) achieves near-universal seroprotection. MMR revaccination, while effective for measles and rubella, shows suboptimal mumps response, suggesting potential need for booster doses or alternative strategies.

Conclusion

Revaccination post-allo-HSCT is safe and effective, with high seroconversion rates for HBV and MMR (excluding mumps). Key determinants of success include pre-transplant vaccination history, antibody titers, and adherence to recommended timelines. These insights inform evidence-based guidelines to optimize post-transplant immunization, reducing morbidity and mortality from vaccine-preventable diseases in this vulnerable population.

doi.org/10.1097/CM9.0000000000003462

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