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Four patients (3 long-term Hodgkin disease survivors and 1 recipient of an allogeneic bone marrow transplant) developed severe infections with Streptococcus pneumoniae after staging splenectomy or due to functional hyposplenism after total body irradiation and bone marrow transplantation. Current guidelines for prevention of infection recommend pneumococcal immunization for patients with Hodgkin disease treated with splenectomy and others with functional hyposplenism. Booster vaccination after 5 years is also advised. Hospital- and community-based vaccination initiatives may help identify at-risk patients.