Avascular necrosis of bone after allogeneic bone marrow transplantation: analysis of risk factors for 4388 patients by the Société Française de Greffe de Moëlle (SFGM)

Abstract

Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single‐centre studies included sufficient patients to enable analysis of the risk factors for developing avascular necrosis. In this multicentre retrospective study the aim was to assess risk factors for this complication in a large number of patients. The population consisted of 4388 patients, recorded in the Société Française de Greffe de Moelle (SFGM) data base, who had undergone a single allogeneic bone marrow transplant between January 1974 and December 1993. 77 patients developed avascular necrosis leading to a 4.3% projected incidence at 5 years. Symptoms developed 2–132 months after transplantation. In these 77 patients a mean of 1.87 joints per patient were affected (range 1–7). The hip joint was the most often affected (88% of patients) and 48% of the patients required joint replacement. All but two patients received steroids for acute and/or chronic graft‐versus‐host disease (GvHD) over a mean period of 15 months. In univariate analysis, among eight factors tested as risk factors for developing avascular necrosis, six were shown to be linked to an increased risk: older age, diagnosis of aplastic anaemia or acute leukaemia, an irradiation‐based conditioning regimen, type of GvHD prophylaxis regimens, acute and chronic GvHD. In multivariate logistic regression analysis, five factors remained significantly associated with an increased risk for developing avascular necrosis: chronic GvHD (odds ratio (OR) 3.52), acute GvHD (OR 3.73), age>16 years (OR 5.81), aplastic anaemia (OR 3.90), and acute leukaemia (OR 1.72). Avascular necrosis is not a rare late complication of allogeneic bone marrow transplantation causing significant morbidity. In this study, older age, initial diagnosis, and GvHD and/or its treatment with steroids emerged as significant risk factors.

Indolent aspergillus arthritis complicating fludarabine-based non-myeloablative stem cell transplantation

“…Other rare causes such as serum sickness 6 or prostaglandin E1-induced arthritis 7 have been described. A more common cause for arthralgia (without arthritis) in this setting, is avascular necrosis, 8 which is often due to chronic high-dose steroid therapy. In cases of infective arthritis, the causative agent is usually bacterial but can occasionally be viral.…”

Non-endocrine late complications in children after allogeneic haematopoietic SCT

“…Onset of clinical symptoms starts once necrosis occurs in the cortical area. AVN may lead to significant morbidity and compromised quality of life with an incidence ranging from 4.3 39 to 19%. 40 Older age at transplant, acute and chronic GvHD, underlying disease and TBI are the main risk factors.…”

“…40 Older age at transplant, acute and chronic GvHD, underlying disease and TBI are the main risk factors. [39][40][41][42] In a recent Italian case-control paediatric study, the risk factors associated with AVN in a multivariate analysis were older age at HSCT, TBI and cGvHD. 43 Continuous and longer use of steroids after HSCT was, however, not associated with the risk of developing AVN, nor the cumulative doses used.…”

Assessing the risk of transplant-related complications and individually tailoring the HSCT procedure in children and adolescents—is it possible?

“…32 Older age at HSCT, acute and cGVHD, type of underlying disease (such as severe aplastic anaemia or ALL) and TBI are the main risk factors for avascular necrosis. 23,24,64 Univariate analysis alone showed that the continuous use of steroids after HSCT is a significant risk factor for avascular necrosis. 64 Pre-transplant screening for avascular necrosis by magnetic resonance imaging 52 is not recommended except in patients who have suspicious clinical signs for this complication, such as persistent bone pain.…”