Predictors of avascular necrosis of bone in long‐term survivors of hematopoietic cell transplantation

Abstract

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. 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. 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). Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition.