Loss of antibodies and response to (re-)vaccination in children after treatment for acute lymphocytic leukemia: a systematic review

Abstract

Intensified chemotherapy regimens resulting in improved survival of children with acute lymphocytic leukemia (ALL) lead to concerns about therapy-induced immune damage reflected by the loss of protection of previous immunizations and the efficacy of (re-)vaccination. The severity of secondary immunodeficiency, however, is not clear and knowledge is based on a limited number of studies. We performed a systematic review on literature concerning vaccination data of children with ALL published since 1980. Eight studies fulfilled the inclusion criteria. Regarding antibody titers after treatment, the number of children who had preserved the defined protection level for antibodies differed widely, ranging from 17 to 98% for diphtheria, 27 to 82% for Bordetella pertussis, 20 to 98% for tetanus, 62 to 100% for poliomyelitis, 35 to 100% for Haemophilus influenzae type B (HiB), 29 to 92% for mumps, 29 to 60% for measles and 72 to 92% for rubella. Most patients however responded to revaccination, demonstrating immunological recovery. Although the designs and results of the included studies varied widely, it can be concluded that cytostatic therapy for ALL in children results in a temporarily reduction of specific antibody levels. Memory is preserved but revaccination may be warranted. This is the first systematic review and the best possible current approximation of chemotherapy-induced immune damage in children after ALL treatment.

Humoral immunity to diphtheria, tetanus, measles, and hemophilus influenzae type b in children with acute lymphoblastic leukemia and response to re‐vaccination

“…Optimal primary vaccination and high herd immunity in the developed countries may reduce infection rates in ALL patients but increased migration and international travel might reduce herd immunity [26].…”

Is immunization necessary after therapy for acute lymphoblastic leukemia (ALL) has been completed?

“…Most published studies find that serum antibody titers often fall below protective levels during therapy and recover to a variable extent following the completion of treatment [2][3][4][5][6][7][8]. Whether or not the fall in titers is synonymous with a lack of protection is debatable as is the depth of chemotherapy-induced immunosuppression [2,3,8,9].…”

“…Whether or not the fall in titers is synonymous with a lack of protection is debatable as is the depth of chemotherapy-induced immunosuppression [2,3,8,9]. An extensive study of 100 patients, treated on BFM, NY I or II, or legacy Pediatric Oncology Group protocols [2] found that survivors were at significantly increased risk of having subprotective antibody titers when assessed 1 year after completion of therapy, but that there was no correlation between antibody titers and therapy received.…”

“…They did not exhibit significant differences in serum quantitative immunoglobulins, lymphocyte numbers, serum complement (CH50), or lymphocyte mitogenesis in response to phytohemaggultinin, concanavalin, and pokeweed mitogen, when compared with age-matched control subjects. In addition, van Tilburg et al [8] published a systematic review of loss of protective antibodies and vaccine response in survivors of ALL therapy. Most patients responded to (re-)vaccination, suggesting preservation of T-memory cells.…”

“…Despite this reassurance that memory and cellular immunity may persist, the frequent documentation of non-protective titers, is of concern and has lead to studies of response to re-vaccination, commonly following the completion of therapy [2,3,5,[7][8][9][10][11]. In this issue of Pediatric Blood & Cancer, Zengin and Sarper [12] describe the response to diphtheria-tetanus and Haemophilus influenza type b (Hib), not only among children who have completed therapy, but also in a group of 36 patients who were receiving maintenance therapy at the time of re-vaccination.…”