title: Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantation.
abstract: BACKGROUND
  Avascular necrosis (AVN) is a debilitating condition reported after chronic steroid use. The purpose of this study was to describe the magnitude of risk in individuals who survived >or=1 years after hematopoietic cell transplantation (HCT), and to investigate the role of immunosuppressive agents such as prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and cyclosporine (CSA) in the development of AVN after HCT.
  
  
  METHODS
  Using a retrospective study design, the authors followed 1346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and disease recurrence. Cox proportional regression techniques were used to identify associated risk factors.
  
  
  RESULTS
  The median age at HCT was 34 years (range, 7 months-69 years), and median length of follow-up for those surviving was 8.2 years. Seventy-five patients developed AVN of 160 joints. The cumulative incidence of AVN at 10 years was 2.9% after autologous HCT, 5.4% after allogeneic matched related donor HCT, and 15% after unrelated donor HCT (P<.001 compared with autologous HCT recipients). For allogeneic transplant recipients, male sex (relative risk [RR], 2.1; 95% confidence interval [95% CI], 1.1-4.0); presence of chronic graft-versus-host disease (RR, 2.2); and exposure to CSA, FK506, prednisone, and MMF rendered patients at increased risk, especially in patients with a history of exposure to >or=3 drugs (RR, 9.2; 95% CI, 2.42-35.24).
  
  
  CONCLUSIONS
  Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition.
authors.affiliation: Department of Population Sciences, City of Hope National Medical Center, Duarte, California 91010-3000, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Campbell
authors.forename: Can-Lan
authors.initials: CL
authors.lastname: Sun
authors.forename: Seira
authors.initials: S
authors.lastname: Kurian
authors.forename: Liton
authors.initials: L
authors.lastname: Francisco
authors.forename: Andrea
authors.initials: A
authors.lastname: Carter
authors.forename: Sameer
authors.initials: S
authors.lastname: Kulkarni
authors.forename: Pablo
authors.initials: P
authors.lastname: Parker
authors.forename: Chatchada
authors.initials: C
authors.lastname: Karanes
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D010020:Osteonecrosis / Q000453:epidemiology / Q000209:etiology*; D012189:Retrospective Studies; D012307:Risk Factors; D017741:Survivors; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous
chemical_list: D007166:Immunosuppressive Agents