1. Reduction in number of investigations Two rather than three nasopharyngeal swabs per subject over study period. Change made as it was felt that little extra information would be gained from a third swab. 2. Change in reporting of SAE’s SAEs only require report up to 28 days after vaccine administration as prolonged follow up is require to monitor for vaccine efficacy rather than safety. A significant number of SAR are likely to occur during the 123 month study period because of the underlying disease and treatment (on-study medications) that the study population are receiving. With the exception of events happening in the first few days after PCV vaccination, it is extremely unlikely that AEs would have been related to IMP or any study procedures. All would be captured but only those in the first 28 days following IMP administration will be formally reported as a SAE.

Inclusion of more detailed statistical analysis plan, with clarification of endpoints

Addition of the following secondary end points for clarity: i) to establish if any of the seroypes are more effective or less effective at inducing protective levels of anti-pneumococcal antibodies in the study ii) to assess whether leukaemia treatment regimen or number of delayed intensifications are associated with (or affect response to) developing protective levels of anti-pneumococcal antibodies iii) to establish whether PCV13 is more or less effective in any of study groups in terms of inducing protective levels of anti-pneumococcal antibodies iv) to investigate the immunogenicity of the vaccine in children who have already had the PCV7 (serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) prior to entering the study Amendment to inclusion criteria- wording in brackets added 'Currently receiving maintenance therapy as per (current UKALL interim guidelines or) UKALL 2003 treatment protocol, or treatment as per UKALL 2003 protocol' Amendment to exclusion criteria Addition of 'Previous immunisation with PCV13 prior to the study'