Avascular osteonecrosis after allogeneic hematopoietic stem-cell transplantation: Diagnosis and gender matter

Background. Avascular osteonecrosis (AVN) is a serious complication of allogeneic stem-cell transplantation (SCT). Acute and chronic graft-versus-host disease and its treatment with steroids are identified as main risk factors. In a single-center, prospective cohort study of patients undergoing allogeneic SCT for chronic myeloid leukemia (CML), acute myeloid leukemia, myelodysplastic syndrome, and acute lymphatic leukemia, we determined the incidence of hip AVN necessitating total arthroplasty (severe adverse event) and performed risk factor analysis. Methods. A total of 255 patients were followed for an observation period of at least 4 years. Thirteen potential risk factors including age, recipient and donor gender, underlying disease and disease stage, conditioning therapy, human leukocyte antigen match, acute or chronic graft-versus-host disease, and immunosuppressive medication were tested in univariate and multifactorial nominal logistic and Cox proportional hazard analyses. Results. Severe adverse events occurred in eight patients (4-year cumulative incidence rate 6.1%). Univariate and multifactorial analysis revealed a diagnosis other than CML and steroid intake as main risk factors (chi(2) model 31.6, P = 0.0005; chi(2) diagnosis 11, P = 0.001; chi(2) steroid 6.8, P = 0.009). The demonstrably strong influence of diagnosis was steroid independent (steroid intake in CML comparable to non-CML). We repeated the analysis in 103 patients without CML (70 with acute myeloid leukemia, 13 with myelodysplastic syndrome, and 20 with acute lymphatic leukemia), excluding 152 patients with CML. Univariate and multifactorial analyses revealed female gender (of both recipient and donor) as risk factors for AVN in addition to steroids. Relative AVN risk for female compared with male donor transplantation was 8.7 (P = 0.01); relative AVN risk for female compared with male recipient transplantation was 4.3 (P = 0.047). Conclusions. Diagnosis and gender are steroid-independent risk factors for severe hip AVN after allogeneic SCT.