title: A prospective study on antibody response to repeated vaccinations with pneumococcal capsular polysaccharide in splenectomized individuals with special reference to Hodgkin's lymphoma.
abstract: BACKGROUND
  Splenectomy is accompanied by a life-long risk of overwhelming postsplenectomy infection (OPSI), mainly caused by polysaccharide (PS) encapsulated bacteria such as Streptococcus pneumoniae. Despite extensive prophylactic efforts the mortality and morbidity rates remain high. The present study was based on a strategy with a predefined vaccination algorithm including repeated 23-valent pneumococcal vaccinations and monitoring of pneumococcal antibody levels. The antibody levels of splenectomized Hodgkin's lymphoma (HL) patients were compared with those patients splenectomized due to immune-mediated cytopenias [autoimmune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP)] and also individuals who were splenectomized because of trauma (TRAUMA).
  
  
  METHODS
  A total of 311 splenectomized individuals were included in this prospective study (208 HL; 15 AIHA; 60 ITP; 28 TRAUMA). Depending on their individual anti-PS antibody levels measured by enzyme-linked immunosorbent assay technique the patients were revaccinated with 23-valent pneumococcal PS vaccine up to four times in accordance with the predefined algorithm. For each vaccination occasion, serum was collected at vaccination, after 1 month +/- 2 weeks (peak), and after 1 year +/- 6 months (follow-up). Patient files, a national population-based database, and microbiological databases were checked for 124 HL patients to identify OPSI.
  
  
  RESULTS
  A significant response was recorded on primary vaccination as well as on two revaccination occasions for HL, AIHA/ITP, as well as TRAUMA patients. None of the variables age, gender, or time elapsed between splenectomy and first pneumococcal vaccination was found to be associated with mean PS antibody levels at prevaccination, peak or follow-up. No severe adverse events were reported. Amongst 124 clinically monitored HL patients, 10 OPSI were recorded in seven patients during the study period. One of these patients, a middle-aged female, died as a result of fulminant pneumococcal bacteraemia, which was her third OPSI during a 7-year period.
  
  
  CONCLUSIONS
  A significant response to pneumococcal PS vaccination was found in all three groups (HL, AIHA/ITP and TRAUMA) of splenectomized patients. Importantly, both primary and repeated vaccinations were safe. Until further knowledge is gained regarding the protective concentration of serotype-specific antibody concentrations we believe that the value of vaccination and frequent revaccination (every 1-5 years) in combination with education of patients and health care professionals and clinical monitoring is beneficial for these patients at risk for OPSI.
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska Hospital and Institutet, Stockholm, Sweden. ola.landgren@ks.se
authors.forename: O
authors.initials: O
authors.lastname: Landgren
authors.forename: M
authors.initials: M
authors.lastname: Björkholm
authors.forename: H B
authors.initials: HB
authors.lastname: Konradsen
authors.forename: M
authors.initials: M
authors.lastname: Söderqvist
authors.forename: B
authors.initials: B
authors.lastname: Nilsson
authors.forename: A
authors.initials: A
authors.lastname: Gustavsson
authors.forename: U
authors.initials: U
authors.lastname: Axdorph
authors.forename: M
authors.initials: M
authors.lastname: Kalin
authors.forename: G
authors.initials: G
authors.lastname: Grimfors
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006689:Hodgkin Disease / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000276:immunology; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology; D013154:Spleen / Q000293:injuries; D013156:Splenectomy / Q000009:adverse effects*
chemical_list: D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial