Diphtheria (D) and tetanus (T) antibody values in children with acute lymphoblastic leukaemia (ALL) after treatment according to Co-ALL 05/92

Abstract

Background: Children and adolescents after acute lymphoblastic leukemia are at risk for a prolonged period of immunodeficiency. Normally within 6 to 9 months after the end of maintenance treatment an adequate immune recovery is present. Factors such as immunity against specific antigens prior to disease (applied baseline vaccination), intensity of treatment and age can play a role in the appearance of antibodies in serum. Diphtheria (D) and Tetanus (T) antibodies are known to appear within 3 to 6 months after end of treatment as a sign of immune recovery and the reinstatement of immunological memory. A number of different questions are of interest: What differences are seen in the antibodies to D and T in children of different ages after treatment with a standardized protocol? What is the influence of post-treatment revaccination with Diphtheria/Tetanus (D/T) and treatment group on the production of D/T antibodies?

Patients and methods: Out of 142 children and adolescents until the age of 16, treated according to the Co-ALL 05/92 protocol, 59 patients were eligible for evaluation: 31 Low-Risk (LR)- and 28 High-Risk (HR) patients. Antibodies against Diphtheria (D) and Tetanus (T) were measured 3-12 months after the end of treatment and after revaccination in case of low antibody levels against D and/or T. In patients without adequate response after repeated revaccination the cellular immunity was examined with a skin test.

Results: After the end of treatment, children in the low-risk (LR)-group showed more frequently adequate antibody titres against D and T than children of the high-risk (HR)-group. Antibodies against T were present in 50% of all patients. After revaccination antibodies against T were found in nearly all patients whereas for D this is only the case in some children. Patients without sufficient antibody levels mainly showed an adequate cellular immunity.

Conclusion: In children and adolescents with ALL after therapy antibody levels of D and T are dependent on treatment intensity. Revaccination leads to an adequate immunological answer against T in most patients , which is not the case for the diphtheria vaccination. Prospective multicenter trials starting together with the ALL-treatment should be able to gain more information about the behavior of antibody levels and the risk of infection from vaccine-preventable disease in immunocompromised patients and thus lead to standardized vaccination guidelines such as immunization with conjugate vaccines already during maintenance treatment.