Avascular Necrosis of Femoral and/or Humeral Heads in Multiple Myeloma: Results of a Prospective Study of Patients Treated With Dexamethasone-Based Regimens and High-Dose Chemotherapy

University of Arkansas at Little Rock, Little Rock, Arkansas, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 09/2005; 23(22):5217-23. DOI: 10.1200/JCO.2005.11.676
Source: PubMed


To assess the prevalence, time of onset, risk factors, and outcome of avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing antineoplastic therapy.
A total of 553 consecutive assessable patients were enrolled onto a treatment protocol consisting of dexamethasone-containing induction chemotherapy, autologous stem-cell transplantation, consolidation chemotherapy, and maintenance with interferon alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no thalidomide (284 patients) throughout the study period.
With a median follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s) developed in 49 patients (9%). Median time to onset of AVN was 12 months (range, 2 to 41 months). Three risk factors for AVN were identified by multivariate analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to 1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192 to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year; P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that of the control group (8% v 10%, respectively; P = .58). AVN-related pain and limited range of motion of the affected joint were present in only nine and four patients, respectively, and four patients underwent hip replacement because of AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect abnormal uptake in the AVN-affected bones.
AVN is a rare and usually asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose, male sex, and younger age, but not thalidomide, increase the risk of AVN.

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    • "ON is an uncommon, long-term complication of hemato-oncologic diseases, such as multiple myeloma,72,73 acute lympoblastic leukemia (ALL),74–76 and chronic myelogenous leukaemia (CML).76,77 "
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    • "As observed in other studies, a history of connective tissue disease or cancer were significant risk factors for ON. This may be confounded by the frequent use of corticosteroids in these populations [4–6, 20]. In addition, overall disease severity/morbidity may also contribute to a higher rate of ON in these populations [1, 4]. "
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