title: Neurological Complications Involving the Central Nervous System After Allogeneic Hematopoietic Stem Cell Transplantation During a Period of Evolution in Transplant Modalities: A Cohort Analysis.
abstract: BACKGROUND
  Neurological complications (NC) after hematopoietic stem cell transplantation (HSCT) are rare events. The evolution of transplant procedures has resulted in improved survival and has allowed elderly patients or those with comorbidity to receive an HSCT. The risk of NC in these patients has still not been well defined. Therefore, we carried out an observational study to estimate the occurrence and identify the risks associated with NC.
  
  
  METHODS
  The study cohort included 452 adult-allogeneic HSCT recipients, transplanted from 1997 to 2012. The median follow up was 1.3 year (0-15.7). A myeloablative regimen was used in 307 patients. Two hundred patients were grafted from matched unrelated donor (MUD), of these, 129 (64.5%) received an in vivo T-cell depletion.
  
  
  RESULTS
  Out of 452 patients, 30 (6.6%) developed NC. Infections were the most frequent causes of NC (30%). Overall survival decreased in patients developing NC (P < 0.001). Univariate survival regression on the cumulative incidence of NC identified period of transplant, linear trend between 4-year periods (1997-2012) (P < 0.001), MUD (P < 0.001), and recipient's age (P = 0.034) as significant risk factors. In multivariate analysis, period of transplant (P < 0.001) and MUD (P = 0.004) remained significant independent risk factors. Matched unrelated donor recipients showed a 3.8-fold elevated risk of developing NC.
  
  
  CONCLUSIONS
  Analysis highlights a temporal trend of incidence of NC that progressively increased over time and confirms a strong association between donor type and risk of NC. Our observations suggest that, although relatively uncommon, NC after allo-HSCT, may become more frequent due to the improved overall survival in recent years.
authors.affiliation: 1 Transplant Bone Marrow Unit, Department of Hematology Oncology Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 2 Istituto Neurologico Nazionale, IRCCS "C. Mondino", Pavia, Italy. 3 Neuroscience Consortium, University of Pavia, Monza Policlinico and Pavia Mondino, Pavia, Italy; C. Mondino National Neurological Institute, Pavia, Italy. 4 Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 5 Molecular Virology Unit, Virology and Microbiology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 6 Department of Hematology Oncology Diseases Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Anna Amelia
authors.initials: AA
authors.lastname: Colombo
authors.forename: Enrico
authors.initials: E
authors.lastname: Marchioni
authors.forename: Luca
authors.initials: L
authors.lastname: Diamanti
authors.forename: Angela Maria
authors.initials: AM
authors.lastname: Di Matteo
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
authors.forename: Milena
authors.initials: M
authors.lastname: Furione
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Virginia Valeria
authors.initials: VV
authors.lastname: Ferretti
authors.forename: Cristiana
authors.initials: C
authors.lastname: Pascutto
authors.forename: Emilio Paolo
authors.initials: EP
authors.lastname: Alessandrino
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002493:Central Nervous System Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D002494:Central Nervous System Infections / Q000453:epidemiology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D019653:Myeloablative Agonists