Discussion
The pathophysiology of cancer and treatment modalities appear to have
long-term effects on various functions of the immune system. This study
focused immune memory from primary vaccines in CCS. Data revealed a loss
of immunity across the vaccine series suggesting immune memory is
impaired by chemotherapy. Cancers involving the immune system, i.e.,
hematological malignancies, resulted in a greater loss of immunity. As
baseline titers were not available for all CCS subjects, the general
population’s immunity rate extracted from the literature was used as the
control. Therefore, all P-values listed are based upon the difference in
this study cohort compared to this control.
The CDC states that protection from the measles, mumps, and rubella
(MMR) vaccine is lifelong.19 One study found
seropositivity rates of 95%, 74%, and 100% for measles, mumps, and
rubella, respectively, 20 years after vaccination with other studies
confirming these results.20,21 While the general
population tends to retain their protective antibodies, the CCS cohort
retained immunity to measles, mumps, and rubella in 77%, 66%, and
76.2%, respectively. This effect was more dramatic in those with
hematological malignancies, with 70%, 58.4%, and 75% retaining
protection to measles, mumps, and rubella, representing a significant
decrease in long-term protection. Of note, mumps was the only titer that
did not reach a P value <0.05 in the study likely due to the
lower antibody persistence of mumps in the control group.
As not all subjects had received the full 5 dose series for tetanus, the
seropositive rate of 85.2% correlating to those who received
<5 doses was utilized for the control.1750% (10/20) of our cohort retained seropositive titers to tetanus. The
hematological malignancy group was more pronounced with only 40% (6/15)
having protective titers.
All subjects received at least one dose of the varicella vaccine. Data
from 1995, prior to the 2006 booster recommendations, demonstrating 99%
seropositivity 6 years after initial vaccination was used as the
control.15 Across all malignancies, 43.4% of patients
retained protective antibody levels with 31.25% of those treated for
hematological malignancies retaining protective antibody levels.
Hepatitis B showed the greatest rates of seronegativity. In a 30-year
study conducted in rural Alaskan villages, 33% of individuals had
surface antibody levels below 10 mIU/ml at 15 years.1833% (6/18) of our total cohort and 23% (3/13) of the hematological
malignancies group retained protective antibody.
This retrospective study has several limitations. There were no
pre-treatment titers for most patients; thus, data was compared to
expected vaccine seropositivity of the general population. Pediatric
malignancies are rare, and the cohort was limited to CSMC patients. This
small data set may not necessarily extrapolate to all CCS.
Despite limitations, these results bolster the idea that CCS likely need
to be revaccinated after completing treatment. CCS, especially
hematological malignancies patients, appear to have lower seropositivity
rates when compared to the general population. After chemotherapy, it
may take months to years for complete immune
reconstitution;7,10,11 however; it is unknown how much
immune recovery is essential for patients to seroconvert after
revaccination.
These findings demonstrate a statistically significant loss of immunity
to measles, rubella, varicella, tetanus and hepatitis B in CCS; however,
no statistically significant difference in mumps antibody persistence.
Future prospective studies are needed to build comprehensive guidelines
for CCS who have not undergone HSCT.
References:
1. Fioredda F. Immunity against hepatitis B and measles vaccination
after chemotherapy for acute lymphoblastic leukaemia in children:
revaccination policy. Rev Bras Hematol Hemoter.2012;34(4):258-259.
2. Zignol M, Peracchi M, Tridello G, et al. Assessment of humoral
immunity to poliomyelitis, tetanus, hepatitis B, measles, rubella, and
mumps in children after chemotherapy. Cancer.2004;101(3):635-641.
3. Fayea NY, Fouda AE, Kandil SM. Immunization status in childhood
cancer survivors: A hidden risk which could be prevented. Pediatr
Neonatol. 2017;58(6):541-545.
4. Patel SR, Bate J, Borrow R, Heath PT. Serotype-specific pneumococcal
antibody concentrations in children treated for acute leukaemia.Arch Dis Child. 2012;97(1):46-48.
5. Patel SR, Ortin M, Cohen BJ, et al. Revaccination of children after
completion of standard chemotherapy for acute leukemia. Clin
Infect Dis. 2007;44(5):635-642.
6. Viana SS, Araujo GS, Faro GB, da Cruz-Silva LL, Araújo-Melo CA,
Cipolotti R. Antibody responses to Hepatitis B and measles-mumps-rubella
vaccines in children who received chemotherapy for acute lymphoblastic
leukemia. Rev Bras Hematol Hemoter. 2012;34(4):275-279.
7. Alanko S, Pelliniemi TT, Salmi TT. Recovery of blood B-lymphocytes
and serum immunoglobulins after chemotherapy for childhood acute
lymphoblastic leukemia. Cancer. 1992;69(6):1481-1486.
8. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing
infectious complications among hematopoietic cell transplantation
recipients: a global perspective. Biol Blood Marrow Transplant.2009;15(10):1143-1238.
9. Bunin N, Small T, Szabolcs P, Baker KS, Pulsipher MA, Torgerson T.
NCI, NHLBI/PBMTC first international conference on late effects after
pediatric hematopoietic cell transplantation: persistent immune
deficiency in pediatric transplant survivors. Biol Blood Marrow
Transplant. 2012;18(1):6-15.
10. Williams AP, Bate J, Brooks R, et al. Immune reconstitution in
children following chemotherapy for acute leukemia. EJHaem.2020;1(1):142-151.
11. van Tilburg CM, van Gent R, Bierings MB, et al. Immune
reconstitution in children following chemotherapy for haematological
malignancies: a long-term follow-up. Br J Haematol.2011;152(2):201-210.
12. Choi YB, Lee NH, Yi ES, Kim YJ, Koo HH. Changes in hepatitis B
antibody status after chemotherapy in children with acute lymphoblastic
leukemia. Pediatr Blood Cancer. 2019;66(12):e27904.
13. Guilcher GMT, Rivard L, Huang JT, et al. Immune function in
childhood cancer survivors: a Children’s Oncology Group review.Lancet Child Adolesc Health. 2021;5(4):284-294.
14. Davidkin I, Jokinen S, Broman M, Leinikki P, Peltola H. Persistence
of measles, mumps, and rubella antibodies in an MMR-vaccinated cohort: a
20-year follow-up. J Infect Dis. 2008;197(7):950-956.
15. Watson B, Rothstein E, Bernstein H, et al. Safety and cellular and
humoral immune responses of a booster dose of varicella vaccine 6 years
after primary immunization. J Infect Dis. 1995;172(1):217-219.
16. Vessey SJ, Chan CY, Kuter BJ, et al. Childhood vaccination against
varicella: persistence of antibody, duration of protection, and vaccine
efficacy. J Pediatr. 2001;139(2):297-304.
17. Borella-Venturini M, Frasson C, Paluan F, et al. Tetanus
vaccination, antibody persistence and decennial booster: a serosurvey of
university students and at-risk workers. Epidemiol Infect.2017;145(9):1757-1762.
18. McMahon BJ, Bruden DL, Petersen KM, et al. Antibody levels and
protection after hepatitis B vaccination: results of a 15-year
follow-up. Ann Intern Med. 2005;142(5):333-341.
19. About MMR and MMRV Vaccines-For Providers. CBC.
https://www.cdc.gov/vaccines/vpd/mmr/hcp/index.html Updated
January 26, 2021. Accessed July 17, 2022.
20. Weibel RE, Buynak EB, McLean AA, Hilleman MR. Long-term follow-up
for immunity after monovalent or combined live measles, mumps, and
rubella virus vaccines. Pediatrics. 1975;56(3):380-387.
21. McQuillan GM, Kruszon-Moran D, Hyde TB, Forghani B, Bellini W, Dayan
GH. Seroprevalence of measles antibody in the US population, 1999-2004.J Infect Dis. 2007;196(10):1459-1464.