Intensive treatment for childhood acute lymphoblastic leukemia reduces immune responses to diphtheria, tetanus, and Haemophilus influenzae type b.
OBJECTIVE
Immunity to diphtheria toxoid (D), tetanus toxoid (T), and Haemophilus influenzae type b (Hib) is affected in children with acute lymphoblastic leukemia (ALL). The aims were to examine immunity and to compare the response to immunization at 1 or 6 months after treatment.


METHODS
Thirty-one patients were immunized with DT and conjugated Hib vaccine (ActHib) at 1 month or 6 months after treatment of ALL with the NOPHO 92 protocol. Antibody levels were determined before and 3 weeks after vaccination. Specific T and Hib antibody-secreting cells of IgG/IgA/IgM isotypes were analyzed in peripheral blood using an ELISPOT technique.


RESULTS
All specific antibody levels decreased during ALL treatment, and protective levels after treatment were noted for 17% against D, 33% against T, and 100% against Hib. No high-risk patient had full D or T protection after treatment. After vaccination all the standard- and intermediate-risk patients achieved full protection against D, T, and Hib. The high-risk group showed insufficient immune response (full protection after vaccination: D 56%, T 22%, Hib 78%). No difference was found between vaccination at 1 month or 6 months after treatment. The poor antibody production in the high-risk group correlated to low numbers of antibody-secreting cells.


CONCLUSIONS
Nonprotective antibody levels against D, T, and Hib after childhood ALL are more common than previously thought. Insufficient immune response was restricted to the high-risk group and was related to a low number of memory B cells in this study. Immunizations should be included in follow-up after childhood ALL, and the policy should be adapted to treatment intensity.
Ek
Torben
T
Department of Pediatrics, Goteborg University, Goteborg, Sweden. torben.ek@medfak.gu.se
Mellander
Lotta
L
Hahn-Zoric
Mirjana
M
Abrahamsson
Jonas
J
D000293:Adolescent; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000187:drug effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors
D000906:Antibodies; D022422:Diphtheria-Tetanus Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D013745:Tetanus Toxoid