Avascular necrosis in long-term survivors after allogeneic or autologous stem cell transplantation: a single center experience and a review

Abstract

Background: The most debilitating skeletal complication of stem cell transplantation (SCT) is avascular necrosis (AVN).

Methods: Two hundred seven consecutive patients were evaluated prospectively for AVN. They survived disease free for more than 180 days after autologous or allogeneic SCT for hematologic malignancies. The diagnosis of AVN in suspicious cases was confirmed by magnetic resonance imaging. Possible correlations with treatments, bone mineral density (BMD), graft versus host disease (GVHD), and in vitro growth of fibroblast progenitors were investigated. Bone mineral density was evaluated by dual-energy X-ray absorptiometry in 100 transplanted patients, and the in vitro growth of fibroblast progenitors was monitored by a fibroblast colony-forming unit (CFU-F) assay in 30 patients after allogeneic SCT.

Results: Twelve patients developed AVN 3-114 months (median, 26 months) following SCT: 10 (10%) after allogeneic SCT and 2 (1.9%) after autologous SCT (P = 0.04). Twenty-five joints were affected by AVN. All patients had femoral head involvement, which was managed with hip replacement in six of them. All but one patient who developed AVN after allogeneic SCT suffered from chronic GVHD (cGVHD). Avascular necrosis occurred 1-4 months after exacerbation or progression of cGVHD. Cumulative dose of steroids was similar in both SCT groups (including steroids given pretransplant for the basic disease), whereas treatment duration was significantly longer in the allogeneic SCT group. Avascular necrosis was related to the decreased number of bone marrow CFU-F colonies in vitro, but not to BMD values.

Conclusions: Avascular necrosis is a skeletal complication that occurs more often after allogeneic than after autologous SCT. Occurrence of AVN symptoms after clinical follow-up of cGVHD suggests that cGVHD requiring long-term steroid therapy is one of the main risk factors for AVN. Avascular necrosis may be facilitated by a severe deficit in the repopulating capacity of bone marrow stromal stem cells after SCT.