Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients With Chronic Lymphocytic Leukaemia.

Background Patients with chronic lymphocytic leukaemia (CLL) are at increased risk of both invasive pneumococcal disease (IPD) and community acquired pneumonia (CAP) caused by Streptococcus pneumoniae. Therefore, international guidelines recommend pneumococcal vaccination for all CLL patients, preferably before initiation of treatment. The recommended vaccination schedule consists of Prevenar13®, a 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by Pneumovax23, a 23-valent polysaccharide vaccine (PPSV23).

The immunological efficacy of this sequential vaccination schedule in CLL patients is unknown. Previous studies have only investigated responses to either PCV13 or PPSV23 alone. Responses to PPSV23 alone are poor in CLL patients. Responses to the 7-valent pneumococcal conjugated vaccine (PCV7) or PCV13 are higher compared to responses to PPSV23, but lower compared to responses in healthy individuals. More advanced disease stage and lower baseline IgG negatively influence responses to vaccination.

The aim of this observational cohort study is to assess the immunogenicity of the currently recommended vaccination schedule of PCV13 followed by PPSV23 in CLL patients.

2. Methods Study design and population As part of routine care, all adult CLL patients naïve to pneumococcal vaccination and cared for in the Amsterdam UMC-location AMC, Flevoziekenhuis, HagaZiekenhuis, Elisabeth-TweeSteden Hospital, Noordwest Ziekenhuisgroep, Albert Schweitzer Hospital and Ikazia Hospital receive one dose of Prevenar13® followed by one dose of Pneumovax23® 2 months later. According to the current local standard of care for immunosuppressed individuals, the response to vaccination will be assessed by measuring pneumococcal antibody levels before and 4-8 weeks after vaccination.

After obtaining informed consent clinical data will be collected by a trained medical student, nurse or research assistant according to a standardized electronic case report form (Castor EDC). Variables included in the case report form are: age, sex, smoking behaviour, Rai stage (I/II/III), past or ongoing chemotherapy, ongoing steroid treatment, past or ongoing therapy with a monoclonal anti-CD20 antibody (and date of last infusion), baseline total IgG level, baseline lymphocyte count, baseline haemoglobin level, baseline platelet level, baseline pneumococcal IgG levels, post-vaccination pneumococcal IgG levels, date of PCV and PPSV23 vaccine administration, date of antibody measurements, comorbidities (Charlson comorbitiy index).