Intensive treatment for childhood acute lymphoblastic leukemia reduces immune responses to diphtheria, tetanus, and Haemophilus influenzae type b

J Pediatr Hematol Oncol. 2004 Nov;26(11):727-34. doi: 10.1097/00043426-200411000-00008.

Abstract

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies / blood
  • Antibody Formation / drug effects*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B-Lymphocytes / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diphtheria-Tetanus Vaccine / administration & dosage
  • Diphtheria-Tetanus Vaccine / immunology*
  • Female
  • Haemophilus Vaccines / administration & dosage
  • Haemophilus Vaccines / immunology*
  • Humans
  • Immunization
  • Immunologic Memory
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Tetanus Toxoid / administration & dosage
  • Tetanus Toxoid / immunology*
  • Time Factors

Substances

  • Antibodies
  • Diphtheria-Tetanus Vaccine
  • Haemophilus Vaccines
  • Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate
  • Tetanus Toxoid