Medical assessment of adverse health outcomes in Dutch childhood cancer survivors; a nationwide project; SKION LATER Q2008 onderzoek:
Impaired splenic function in long-term survivors of childhood cancer; diagnostic and therapeutic strategies.

The SKION LATER Q2008 spleen study focuses on the decreased functioning of the
spleen in long term survivors of childhood cancer. Patients with functional or
anatomic asplenia are at significantly increased risk of overwhelming
infection, particularly involving the encapsulated bacteria Streptococcus
pneumoniae and Haemophilus influenzae. According to the current guidelines,
patients should receive pneumococcal vaccination to prevent infection. However,
in patients with lymphoproliferative disorders, the antibody level declines
more rapidly and insufficient vaccinal response has been reported in
splenectomized patients with hematological diseases. Therefore, it is important
to study the functioning of the spleen in the population of survivors of
childhood cancer who have received total body irradiation, irradiation of the
spleen or those who have undergone splenectomy. Next to that, the level and
extent of the antibody response needs to be studied in patients who have been
vaccinated.

Primary aims:
1. To assess the efficacy of pneumococcal vaccination in patients with impaired
splenic function after cancer therapy.
2. To compare the number of IgM memory B-cells of survivors after splenectomy
with survivors who received TBI, and survivors irradiated over the spleen, in
order to investigate the value of IgM memory B-cells in the assessment of
splenic function.
Secondary aims:
1. To examine the vaccination status of long-term survivors with impaired
splenic function.
2. To analyze, in a cross-sectional study, the duration of antibody response
after pneumococcal vaccination in long term survivors.
3. To examine the relation between IgM memory B cells and antibody response
after pneumococcal vaccination in survivors with impaired splenic function
after cancer therapy.

Medical assessment and additional diagnostic tests:
- Medical history: Date of splenectomy/ date, dose and field of irradiation.
Vaccinations and date of vaccinations, antibiotic prophylaxis, severe
documented infections.
- Blood analysis T=0: Survivors (n=100): Flow cytometry-based
immunophenotyping
- Blood analysis T=0: Survivors (n=469) Pneumococcal antibodies MOPA recently
modified into a multiplex opsonophagocytosis killing assay

Long term survivors with hypo-or asplenia:
Prophylactic vaccination according to the RIVM guidelines for the survivors who
were not vaccinated according to the guidelines (patient care; max 469
survivors): T=1: Three weeks after the last vaccination: Pneumococcal
antibodies.

Vaccination of childhood cancer survivors will be performed according to the
Dutch clinical guidelines for patients with impaired splenic function (regular
patient care). Burden for patients is an extra visit to the local hospital for
a venapuncture to obtain 4 ml blood, 3 weeks after the Pneumovax vaccination.
Besides 10 ml extra blood will be taken for research questions when patients
get venapunctures for regular patient care.