Original Article
Immunodeficiency in children with acute lymphoblastic leukemia after completion of modern aggressive chemotherapeutic regimens

https://doi.org/10.1016/j.jpeds.2004.12.043Get rights and content

Objective

To determine the prevalence, duration, and a potential cause of humoral defect(s) in children with acute lymphoblastic leukemia (ALL) at least 1 year after completion of chemotherapy.

Study design

Antibody titers for mumps, rubeola, rubella, tetanus and diptheria toxoid, poliovirus serotypes 1, 2,and 3, Haemophilus influenzae type b, varicella, and hepatitis B were obtained from 100 children with ALL. Children with non-protective titers to these microbial antigens were re-vaccinated and re-studied after anamnestic vaccine challenge.

Results

The percent of children with ALL who had protective titers was markedly less than that anticipated for immunized control subjects. Longitudinally, many titers fluctuate between protective and non-protective antibody responses after re-immunization. The chemotherapy protocol used did not affect the ability of these children to express protective antibody responses. T-, B-, and NK-cell numbers and proliferative responses to mitogens were all normal. Age correlated with titer results for certain vaccines.

Conclusions

Children in remission from ALL have a high prevalence of humoral immune defects that are not related to any specific chemotherapy regimen. This antibody deficiency may place children with ALL at risk for the development of these bacterial and viral diseases, even after completion of chemotherapy. Pediatricians, oncologists, or both should periodically monitor humoral immunity after chemotherapy and re-vaccinate these children, as needed, to ensure prolonged immunoprotection.

Section snippets

Patient Selection and Study Design

We performed a chart review to identify children with precursor T- or precursor B-cell ALL who had been treated and observed at the Schneider Children's Hospital. Classification of ALL phenotype was made on the basis of a multiparameter flow cytometric analysis.23 The children had been treated with either the modified BFM1, 22 or another MACR, including the risk-defined Pediatric Oncology Group (POG 9201, 9405, 9605, and 9406), and the NY I24 and NY II25 protocols. These other MACR protocols

Patient Population

All children were treated at the time of initial diagnosis of ALL; 77 children were treated with a modified BFM protocol,1, 22 and 23 others were treated with MACR. Eight-nine percent of the children had precursor B-cell ALL, and 11% had precursor T-cell ALL. Of the patients (n = 65) who had genotype data available, 7 had T-cell ALL, whereas the remainder of patients had pre-B-cell ALL. We categorized the pre-B-cell genotypes into 3 groups: normal chromosome number (17/58), hyperdiploidy (27/58),

Discussion

A large number of these children persistently failed to make and maintain protective antibody responses to viral vaccines, bacterial vaccines, or both. Furthermore, an even larger number of children showed fluctuation in their ability to express and maintain protective antibody responses. This indicates that children, after chemotherapy, are more likely to be at risk of serious infection than would be predicted when only children who persistently fail to make protective antibodies are

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      Second, albeit revaccination enables most of the affected children to recover protective titres, a subset of patients show a persistent deficiency in their antibody levels. There are several studies with similar results, which have also described an association between loss of vaccine-induced antibodies and a lower age at the time of diagnosis [11–17]. This suggests that the less mature B-cell compartment in younger individuals may be more vulnerable and susceptible to chemotherapy-induced deficiencies.

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