Predictors of avascular necrosis of bone in long-term survivors of hematopoietic cell transplantation.
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.
Campbell
Stephanie
S
Department of Population Sciences, City of Hope National Medical Center, Duarte, California 91010-3000, USA.
Sun
Can-Lan
CL
Kurian
Seira
S
Francisco
Liton
L
Carter
Andrea
A
Kulkarni
Sameer
S
Parker
Pablo
P
Karanes
Chatchada
C
Forman
Stephen J
SJ
Bhatia
Smita
S
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
D007166:Immunosuppressive Agents