Loss of measles, mumps, and rubella immunity in pediatric cancer survivors following chemotherapy

Abstract

Objectives

Pediatric cancer survivors are at increased risk for vaccine-preventable diseases due to treatment-related immunosuppression. This study aimed to assess serological status for measles, mumps, and rubella (MMR) following chemotherapy and identify factors associated with antibody loss.

Results

Fifty-four pediatric cancer survivors (mean age 12.5 years) were evaluated at a median of 2.5 years (IQR 1.2, 5.4) after completing chemotherapy. All participants had received at least one MMR dose before their cancer diagnosis and had completed treatment at least six months prior. Overall, 43 patients (79.6%) were seronegative for at least one MMR component. Seronegativity was highest for measles (64.8%), followed by mumps (55.6%) and rubella (35.2%). Measles seronegativity was significantly associated with a longer interval since chemotherapy (> 5 years; p = 0.04) and older age at receipt of the second MMR dose (mean 86.4 vs. 44.9 months; p = 0.002). No significant associations were observed for mumps or rubella seronegativity. These findings indicate a substantial decline in MMR immunity after chemotherapy and support the incorporation of routine post-chemotherapy revaccination into survivorship care, especially in settings where serologic testing is not readily available.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13104-025-07617-1.

Introduction

Pediatric cancer survivors are at increased risk of vaccine-preventable diseases due to treatment-related immunosuppression. Chemotherapy impairs both the number and function of immune cells, particularly T- and B-lymphocyte responses, resulting in immune deficits that may persist for months or even years after treatment [1–5]. In addition, many children are diagnosed before completing routine immunizations, and delays or missed vaccinations, combined with waning immunity, further increase the risk of developing vaccine-preventable diseases [4–6]. Previous studies have shown substantial loss of protective antibodies in this population, with reported seronegativity rates varying by treatment intensity, time since therapy, and individual host factors [2, 3, 7–10]. Despite this heterogeneity, many survivors lack protective antibodies, highlighting the potential long-term impact of chemotherapy on immunity.

Among vaccine-preventable diseases, measles, mumps, and rubella (MMR) warrant particular attention because of their high transmissibility and, in the case of measles, significant morbidity and mortality even among otherwise healthy children. These risks are further amplified in immunocompromised survivors. As MMR vaccination is an integral component of Thailand’s national immunization program (NIP), maintaining immunity is essential for individual protection, school participation, and broader community safety. Furthermore, MMR serological assays are standardized and widely available, providing a practical measure of post-chemotherapy humoral immunity. Loss of vaccine-derived immunity may also restrict daily activities, increase caregiver anxiety, and contribute to outbreak vulnerability within clusters of non-immune individuals.

While guidelines for revaccination are well-established for children undergoing hematopoietic stem cell transplantation (HSCT) [11], no universal protocol exists for those treated with chemotherapy alone. Current recommendations vary substantially. The Centers for Disease Control and Prevention (CDC) recommends reinitiating immunizations as early as three months after chemotherapy [12], whereas UK guidelines suggest waiting at least six months [13]. In Thailand, a single MMR dose is recommended three months post-therapy, but timing and serologic testing are left to clinician discretion. Taken together, these inconsistencies reflect ongoing uncertainty about how best to balance the need for early protection against vaccine-preventable diseases with the need for adequate immune reconstitution after chemotherapy. The absence of harmonized recommendations highlights an important gap in post-treatment survivorship care.

To date, no published data have systematically described post-chemotherapy MMR serostatus among pediatric cancer survivors in Thailand. Generating local evidence is essential to inform national immunization policies and survivorship care practices. Accordingly, this study aimed to evaluate the serological status of measles, mumps, and rubella among pediatric cancer survivors and to identify clinical factors associated with loss of protective antibodies.

Methods

Study design and participants

A cross-sectional study was conducted at the Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Bangkok, Thailand, between January and December 2022. Eligible participants were pediatric cancer survivors aged 2–20 years who had completed chemotherapy at least six months before enrollment and had received at least one MMR vaccine dose before diagnosis. Exclusion criteria included known immunodeficiency, relapse, HSCT, or prior natural MMR infection. Based on previous reports of MMR seronegativity in childhood cancer survivors [2, 3, 7–10], and assuming an expected seronegativity of 35% and a 95% confidence level with a desired precision of +/-12%, the required sample size was estimated to be 61 participants using a single proportion formula. The study was approved by the Human Research Ethics Committee, Faculty of Medicine Ramathibodi Hospital, Mahidol University (COA. MURA2022/25). Written informed consent was obtained from the parents or legal guardians. Assent forms were obtained from patients aged 7–18 years old. The study was conducted according to the declaration of Helsinki.

Data collection and serologic testing

Clinical data, including diagnoses, chemotherapy regimens, and current medications, were retrieved from medical records. Vaccination history was obtained from parental interview and immunization handbooks where available, with discrepancies resolved by cross-checking against hospital records. Although some limitations in parental recall are possible, most vaccination records were verified through written documentation, minimizing the likelihood of misclassification.

According to Thailand’s NIP, the first MMR dose is administered at 9 months of age. The second dose was originally scheduled at 4–6 years, but this was shifted to 2.5 years in 2014 and subsequently to 1.5 years in 2020 to provide earlier protection. All participants had received MMR vaccine according to this schedule prior to their cancer diagnosis. During the study period, routine post-chemotherapy revaccination was not part of the institutional immunization policy; therefore, none had received MMR revaccination following completion of chemotherapy. Serum IgG antibodies against measles, mumps, and rubella were measured using the LIAISON^® chemiluminescent immunoassay (CLIA) platform (DiaSorin, Saluggia, Italy). Seropositivity was defined using assay-specific thresholds: >16.5 AU/mL for measles, > 11 AU/ml for mumps, and > 10 IU/ml for rubella.

Statistical analysis

Categorical variables were summarized as frequencies and percentages and compared using Chi-square or Fisher’s exact tests. Continuous variables were expressed as means with standard deviations (SD) or medians with interquartile ranges (IQR), depending on their distribution, and compared using the Mann-Whitney U test. Associations between categorical clinical variables and seronegativity for measles, mumps, and rubella were assessed using univariate logistic regression. Given the modest sample size and limited number of outcome events, multivariable models were not prespecified to avoid overfitting. All variables included in the analyses were complete, and no imputation was required. Statistical significance was defined as p < 0.05. All analyses were performed using Stata version 15.1 (StataCorp., College Station, TX, USA).

Results

A total of 54 patients were enrolled, comprising 29 males (53.7%) and 25 females (46.3%). The median age at cancer diagnosis was 6.2 years (IQR 3.4, 11.0) and the mean age at the time of serologic testing was 12.5 years (SD ± 4.8). Hematologic malignancies accounted for 30 patients (55.6%), while 24 patients (42.6%) had solid tumors. Of the patients, 28 patients (51.9%) had received chemotherapy alone, while 26 patients (48.1%) received additional adjunctive treatments such as surgery or radiotherapy. The median age at first MMR vaccination was 9.6 months (IQR 9.4, 10.2), and 45 participants had received a second dose at a median age of 4.9 years (IQR 3.6, 6.2). The median interval between the end of chemotherapy and serologic testing was 2.5 years (IQR 1.2, 5.4). Baseline characteristics of study participants are detailed in Table 1.

Table 1.

Baseline demographic and clinical characteristics of study participants

Characteristic (N = 54)	Value
Male, n (%)	29 (53.7)
Age at cancer diagnosis (years) median, IQR	6.2 (3.4, 11)
Type of cancers, n (%)
- Hematologic malignancy - Solid tumor	31 (57.4) 23 (42.6)
Age at antibody testing (years) mean ± SD	12.5 ± 4.8
MMR vaccination before chemotherapy, n (%)
- One dose - Two doses	9 (16.7) 45 (83.3)
Age at first dose MMR vaccination (months) median, IQR	9.6 (9.4, 10.2)
Age at second dose MMR vaccination (years) median, IQR*	4.9 (3.6, 6.2)
Interval from end of chemotherapy to antibody testing (years) median, IQR)	2.5 (1.2, 5.4)
Treatment modality, n (%)
- Chemotherapy alone - Chemotherapy + other modalities (surgery or radiotherapy)	28 (51.9%) 26 (48.1%)

SD: standard deviation; IQR: inter quartile range; MMR: measles, mumps, and rubella

*Among 45 patients who received two doses of MMR before cancer diagnosis

Of the 54 patients, 43 (79.6%) were seronegative for at least one of the three viruses. Among them, 23 (42.6%) were seronegative for two viruses, and 9 patients (16.7%) lacked protective antibodies against all three. Only 11 patients (20.4%) were seropositive for all three viruses. The seronegativity rates for measles, mumps, and rubella were 64.8%, 55.6%, and 35.2%, respectively (Table 2). Clinical and vaccination details of the 11 patients who remained seropositive for all three viruses, along with the overall distribution of serological status for measles, mumps, and rubella, are provided in Supplementary Tables 1 and 2, respectively.

Table 2.

Post-chemotherapy serostatus for measles, mumps, and Rubella

Serostatus category	N (%)
Combined MMR serostatus
• Seropositive for all 3 viruses • Seronegative to ≥ 1 virus - Seronegative to all 3 viruses (subset)	11 (20.4) 43 (79.6) 9 (16.7)
Seronegativity by individual virus
• Measles • Mumps • Rubella	35 (64.8) 30 (55.6) 19 (35.2)

Seronegativity to ≥ 1 virus includes all children who lacked protective antibodies against at least one component (measles, mumps, or rubella). The subset seronegative to all 3 viruses is included within this group

Measles seronegativity was more frequently observed among patients who had completed chemotherapy more than five years prior to antibody testing (37.1% vs. 10.5%, p = 0.04). Additionally, measles-seronegative children had received their second MMR dose at a significant older age (median 86.4 months, IQR 71–100) than seropositive individuals (median 44.9 months, IQR 32–57, p = 0.002). No significant associations were observed between seronegativity for measles, mumps, or rubella and patient gender, age at cancer diagnosis, type of malignancy, or treatment modality (Table 3).

Table 3.

Factors associated with measles, mumps, and Rubella seronegativity

	Measles				Mumps				Rubella
	Seropositive N = 19	Seronegative N = 35	p-value	OR (95%CI)	Seropositive N = 24	Seronegative N = 30	p-value	OR (95%CI)	Seropositive N = 35	Seronegative N = 19	p-value	OR (95%CI)
Male, n (%)	10 (52.6)	15 (42.9)	0.49	0.68 (0.22–2.07)	10 (41.7)	15 (50)	0.54	1.40 (0.47–4.13)	18 (51.4)	7 (36.8)	0.31	0.55 (0.18–1.73)
Age at diagnoses, median (IQR)
≤ 5 years	8 (42.1)	16 (45.7)	0.80	1.16 (0.37–3.58)	11 (45.8)	13 (43.3)	0.85	0.90 (0.31–2.66)	18 (51.4)	6 (31.6)	0.17	0.44 (0.13–1.41)
> 5 years	11 (57.9)	19 (54.3)			13 (54.2)	17 (56.7)			17 (48.6)	13 (68.4)
Malignancy types, n (%)
Hematologic malignancy	11 (57.9)	20 (57.1)	0.96	0.97 (0.31–3.00)	12 (50)	19 (63.3)	0.33	1.73 (0.58–5.15)	18 (51.4)	13 (68.4)	0.23	2.05 (0.63–6.61)
Solid tumor	8 (42.1)	15 (42.9)			12 (50)	11 (36.7)			17 (48.6)	6 (31.6)
Treatment, n (%)
Chemotherapy	9 (47.4)	19 (54.3)	0.63	1.32 (0.43–4.04)	10 (41.7)	18 (60)	0.18	2.10 (0.70–6.26)	15 (42.9)	13 (68.4)	0.08	2.89 (0.89–9.37)
Chemotherapy + other modalities	10 (52.6)	16 (45.7)			14 (58.3)	12 (40)			20 (57.1)	6 (31.6)
Interval from end of treatment to antibody testing, median (IQR)
≤ 5 years	17 (89.5)	22 (62.9)	0.04	0.20 (0.04–1.00)	19 (79.2)	20 (66.7)	0.31	0.53 (0.15–1.83)	25 (71.4)	14 (73.7)	0.86	1.12 (0.32–3.94)
> 5 years	2 (10.5)	13 (37.1)			5 (20.8)	10 (33.3)			10 (28.6)	5 (26.3)
Age at receiving MMR vaccine (months), median (IQR)
1st MMR	9.4 (9.0, 12)	9.0 (9.0, 9.7)	0.37		10.6 (9.3, 13.9)	9.4 (9.1, 10.4)	0.97		9.0 (9.0, 12.0)	9.0 (9.0, 9.4)	0.16
2nd MMR	44.9 (32, 57)	86.4 (71, 101)	0.002		51.8 (37, 67)	64 (48, 80)	0.15		58 (41, 74)	60 (46, 74)	0.99

OR; odds ratio, CI; confidence interval, IQR; interquartile range, MMR; measles, mumps, rubella

Discussion

This study evaluated the serological status of measles, mumps, and rubella among pediatric cancer survivors following chemotherapy. At a median of 2.5 years post-treatment, 79.6% of patients lacked protective antibodies against at least one MMR component, with measles exhibiting the highest seronegativity rate, followed by mumps and rubella. These findings highlight the immunosuppressive effects of chemotherapy and underscore the importance of timely revaccination in this vulnerable population.

The high overall seronegativity rate observed in this cohort reflects the known immunosuppressive effects of chemotherapy, which impairs both cellular and humoral immunity by depleting T and B lymphocytes, including memory cells essential for long-term protection [14]. Previous studies have reported wide variability in seronegativity rates among pediatric cancer survivors, ranging from 24 to 59% for measles, 26–47% for mumps, and 19–45% for rubella [2, 3, 7–10]. This variability likely reflects heterogeneity in treatment intensity, vaccination schedules, and intervals between chemotherapy and antibody testing. These findings highlight the importance of context-specific factors in shaping immune recovery. In particular, the timing of antibody testing remains a critical determinant. In this study, the median interval to serologic testing was 2.5 years, which may explain some variation compared to previous studies reporting intervals from 3 months to 5 years [2, 3, 8].

Several mechanisms may plausibly contribute to the high measles seronegativity (64.8%) observed in this cohort. In Thailand’s NIP, the first MMR dose is given at 9 months, earlier than the 12–15 months recommended in many high-income settings. Early vaccination may coincide with residual maternal antibodies, potentially interfering with vaccine-induced immune responses and long-term immunity. The second MMR dose was originally scheduled at 4–6 years but has been progressively shifted to younger ages to enhance early protection. Most children in this cohort were diagnosed with cancer around age 6 and therefore likely completed the recommended MMR series before undergoing chemotherapy. In addition, chemotherapy-related immunosuppression and the natural waning of vaccine-derived antibody overtime may contribute to the diminished seroprotection observed [15, 16]. We also observed that measles-seronegative children had received their second MMR dose at a significantly older age compared to those who remained seropositive, which may reflect a shorter interval between vaccination and the onset of chemotherapy, limiting time for effective immune priming. This finding highlights the potential importance of optimizing both vaccine timing and the interval before immunosuppressive therapy, however, the modest sample size limits the strength of inference.

In this study, 55.6% of participants were seronegative for mumps, which is higher than previous reports in pediatric cancer survivors [2, 3, 7, 8]. Notably, waning mumps immunity has also been documented in healthy populations. A large German serosurvey reported a mumps seronegativity rate of 15.3% among children and adolescents aged 1–17 years [17], while a recent Thai study demonstrated that only 51.3% of healthy children retained protective titers five years following vaccination [18]. While the seronegativity rate observed in our cohort was slightly higher, this suggests that natural waning of mumps immunity may be more substantial than previously recognized. This resemblance to rates seen in healthy populations underscores the vulnerability of immunocompromised children and reinforces the need for revaccination strategies tailored to ensure long-term protection in pediatric cancer survivors.

Rubella seronegativity was the lowest among the three viruses evaluated, observed in 35.2% of participants, indicating relatively preserved humoral immunity against rubella following chemotherapy. This finding aligns with previous studies suggesting that rubella-specific antibodies may exhibit greater resilience to chemotherapy-induced immunosuppression [2, 3, 7–9]. Although the rubella seropositivity rate in this cohort (64.8%) was lower than the 87–97% typically observed in healthy pediatric populations [15, 16, 19, 20], it exceeded the corresponding rates for measles and mumps within the same cohort. This relative sustained rubella immunity may reflect more robust memory B-cell responses or enhanced long-term antibody persistence compared to measles and mumps [21].

The absence of standardized post-chemotherapy immunization protocols in Thailand, where timing and serologic testing are left to clinician discretion, likely contributed to the high seronegativity rates observed. Notably, 8 of 23 patients (34.8%) with solid tumors remained seropositive for all three viruses, compared to only 3 of 31 (9.7%) with hematologic malignancies, suggesting greater immune impairment in the latter group. These findings support the integration of systematic MMR revaccination into survivorship care, particularly those with hematologic malignancies who appear at higher risk of seronegativity. In low- and middle-resource settings, logistical constraints and limited access to serologic testing make universal revaccination without prior antibody testing a pragmatic and operationally feasible strategy to restore protection. By contrast, in healthcare systems where serologic testing is readily available and accessible, targeted antibody testing may be appropriate in selected circumstances.

Conclusion

Pediatric cancer survivors demonstrate high rates of seronegativity rates to measles, mumps, and rubella, particularly those with hematologic malignancies. These findings support the implementation of routine MMR revaccination after chemotherapy, without relying on serologic testing, to ensure adequate protection in this vulnerable population.

Limitations

This study has several limitations. First, it was conducted at a single tertiary center with a relatively modest sample size, which may limit the generalizability of the findings and reduces statistical power, particularly for subgroup analyses. Second, the limited cohort size precluded multivariate analysis to identify independent predictors; therefore, residual confounding cannot be excluded. Third, the absence of a healthy control group restricts the ability to distinguish chemotherapy-related effects from background waning of vaccine-derived immunity in the general population. Finally, we focused exclusively on humoral immunity and did not evaluate cellular immune responses, which are also critical for long-term protection. Future multicenter studies with larger cohorts, healthy control groups, and integrated evaluation of both humoral and cellular immune responses are warranted.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

MMR

Measles, Mumps, and Rubella

HSCT

Hematopoietic stem cell transplantation

NIP

National Immunization Program

IgG

Immunoglobulin G

AU

Arbitrary units

SD

Standard deviation

IQR

Interquartile range

Author contributions

KN designed the framework of the study, collected the data, analyzed and interpreted the data, and drafted the manuscript. SB designed the framework of the study, analyzed and interpreted the data, critically revised the manuscript, and approved the final version. NA critically revised the manuscript and approved the final version. SC, SP, and CT provided patient care and contributed clinical insights.

Funding

Open access funding provided by Mahidol University. The work was supported by funding from Faculty of Medicine Ramathibodi Hospital, Mahidol University.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the Human Research Ethics Committee, Faculty of Medicine Ramathibodi Hospital, Mahidol University (COA. MURA2022/25). Written informed consent was obtained from participants aged 18 years and older and participants’ legally authorized representatives if participants aged < 18 years. Assent was obtained from participants aged 7–18 years old. The study adhered to the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.