title: Invasive pneumococcal disease following adult allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  Allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients are at high risk of invasive pneumococcal disease (IPD). We investigated the incidence and risk factors of IPD in alloHSCT recipients from 4 regional transplant centers over an 11-year period. This study aimed to inform future improvements in post-transplant care.
  
  
  METHODS
  We conducted a retrospective nested 1:2 case-control study in patients aged ≥18 years who underwent alloHSCT between 2001 and 2011 in 4 major allogeneic transplant centers. Controls were matched with IPD cases on the basis of conditioning intensity and donor relationship (related or unrelated). Demographics and clinical characteristics of cases and controls were summarized. Univariate analysis of risk factors in matched case-control sets, and multivariate conditional logistic regression to control for confounding, were performed.
  
  
  RESULTS
  In 23 alloHSCT recipients, 26 IPD episodes were identified. The cumulative incidence over 11 years was 2.3% (95% confidence interval [CI] 1.45-3.15) and the incidence density 956 per 100,000 transplant years of follow-up (95% CI 580-1321). Multivariate risk factor analysis and backwards elimination showed a significant positive association between mycophenolate mofetil (MMF), hyposplenism/asplenia, and IPD, whereas trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis for Pneumocystis jirovecii pneumonia (PJP) was associated with lower odds of IPD cases. Of alloHSCT recipients with IPD, 38.5% required intensive care, and, of deaths documented in cases over the period of review, 30% were attributable to IPD. Serotypes causing IPD matched currently available vaccines in 15/22 (68.1%) episodes.
  
  
  CONCLUSIONS
  The incidence of IPD in alloHSCT recipients is an important cause of morbidity and mortality, with rates of disease being many fold higher than the general population. Patients with evidence of hyposplenism/asplenia define a high-risk group in the alloHSCT population for IPD, and the independent association with IPD and MMF in the adjusted model from this study requires further evaluation. The occurrence of post-transplant IPD may be reduced by measures such as vaccination with both 13-valent and 23-valent pneumococcal vaccines. TMP/SMX prophylaxis for the prevention of PJP may offer incidental protection against IPD in alloHSCT recipients.
authors.affiliation: Faculty of Medicine, University of New South Wales, Randwick, New South Wales, Australia; Department of Infectious Diseases, Prince of Wales Hospital, Randwick, New South Wales, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Torda
authors.forename: Q
authors.initials: Q
authors.lastname: Chong
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: A
authors.initials: A
authors.lastname: Dodds
authors.forename: M
authors.initials: M
authors.lastname: Greenwood
authors.forename: S
authors.initials: S
authors.lastname: Larsen
authors.forename: N
authors.initials: N
authors.lastname: Gilroy
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D016022:Case-Control Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D012189:Retrospective Studies; D012307:Risk Factors; D012703:Serotyping; D013154:Spleen / Q000002:abnormalities; D013296:Streptococcus pneumoniae / Q000145:classification; D014184:Transplantation, Homologous; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D009173:Mycophenolic Acid
keywords: HSCT; incidence; invasive pneumococcal infection; serotype; vaccination