title: Intensive treatment for childhood acute lymphoblastic leukemia reduces immune responses to diphtheria, tetanus, and Haemophilus influenzae type b.
abstract: 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.
authors.affiliation: Department of Pediatrics, Goteborg University, Goteborg, Sweden. torben.ek@medfak.gu.se
authors.forename: Torben
authors.initials: T
authors.lastname: Ek
authors.forename: Lotta
authors.initials: L
authors.lastname: Mellander
authors.forename: Mirjana
authors.initials: M
authors.lastname: Hahn-Zoric
authors.forename: Jonas
authors.initials: J
authors.lastname: Abrahamsson
mesh_terms: 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
chemical_list: D000906:Antibodies; D022422:Diphtheria-Tetanus Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D013745:Tetanus Toxoid