Assessment of Immunization Status Following Non-HSCT Chemotherapy-treated Pediatric Leukemia Survivors

BACKGROUND: Chemotherapy for pediatric leukemia induces profound immunosuppression, resulting in waning protection against vaccine-preventable diseases. Despite high survival rates, standardized revaccination protocols for non-transplant survivors remain controversial. We aimed to assess the serologic immunity to measles, mumps, rubella, and varicella among pediatric leukemia survivors and to identify clinical and treatment-related determinants of immune persistence. METHODS: In this retrospective cohort study, 192 pediatric leukemia survivors treated with non-HSCT chemotherapy at Phoenix Children's Hospital (2021 to 2023) underwent serologic testing for measles, mumps, rubella, and varicella IgG antibodies. Demographic, clinical, and immunization data were retrieved from institutional and state registries. Associations between patient characteristics and serologic immunity were analyzed using logistic regression. RESULTS: At a mean of 6.51 years following chemotherapy completion, the overall seropositivity rates were 37.0% for measles, 40.6% for mumps, 70.8% for rubella, and 24.5% for varicella. Survivors who received post-chemotherapy vaccination demonstrated significantly higher seropositivity for rubella (81.9% vs. 64.1%, P=0.004) and varicella (35.6% vs. 16.3%, P=0.005), with higher but non-significant seropositivity for measles and mumps. Low-risk B-cell acute lymphoblastic leukemia (ALL) patients exhibited higher immunity compared with high-risk patients, with significant differences observed for mumps (53.6% vs. 24.6%, P=0.0009) and rubella (81.2% vs. 66.7%, P=0.039). Moreover, a shorter interval from therapy completion was associated with improved rubella immunity (adjusted OR=0.753; 95% CI: 0.66-0.86). Post-chemotherapy revaccination was independently associated with increased odds of rubella (adjusted OR=4.89; 95% CI: 1.762-13.572) and varicella (adjusted OR=2.65; 95% CI: 1.124-6.26) immunity. CONCLUSION: Substantial attenuation of vaccine-derived immunity persists years after chemotherapy completion in pediatric leukemia survivors. Both treatment intensity and absence of post-chemotherapy revaccination contribute to impaired long-term humoral immunity. These findings support routine revaccinations for all non-transplant pediatric leukemia survivors and underscore the need for risk-adapted, individualized survivorship immunization strategies.