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Reply to Laws et al.: Vaccination after the end of chemotherapy for acute lymphoblastic leukaemia in children

To the Editor: Our recent report about the need for re-immunisation of children treated for acute lymphoblastic leukaemia (1) raised many comments (2–4). The major point raised by Laws et al. is that the leukaemia population is heterogeneous and due to risk stratification (i.e. high risk vs. low and standard risks), the patients received different exposure to chemotherapy regimens, resulting in variable degrees of imunosuppression and, as a consequence, in a different immunological reconstitution. For this reason they claim that our recommendations of no vaccination or booster to the general leukaemic population may be considered too extensive. We agree that patients treated with very intensive regimens could present a more severe and prolonged immunosuppression and should therefore probably be evaluated more carefully (4, 5). Even trying to solve the bias of sample selection, the general approach to the evaluation of residual immunity after chemotherapy presents at least three main problems: (i) the correct method of evaluation of residual protection against vaccinal antigens, (ii) the different ability to respond to vaccinal antigens in cancer and non-cancer patients both after first-line immunisation and after booster and (iii) the progressive loss of antibody titers against vaccinal antigens with time, which is probably related to a natural history (6). On the basis of available knowledge we cannot also completely exclude that children who received antineoplastic chemotherapy have the same behavior as normal subjects and therefore should not be re-immunised. Therefore, since at present no answer can be considered conclusive and many questions are unanswered (1, 7–10) we completely agree with Laws et al. about the need for prospective, multicentre studies performed in countries that use similar antineoplastic protocols and vaccination schedules, to evaluate immune response to vaccines in children after anti-leukaemic chemotherapy, stratified according to treatment intensity. Because of the normal antibody titer reduction observed in the healthy population, only the comparison of antibody titers against vaccinal antigen between cancer children and matched healthy controls, could clarify which paediatric cancer patients (both leukaemias and solid tumours) must be revaccinated, at which time, and against what.