Osteonecrosis in Adults With Acute Lymphoblastic Leukemia: An Unmet Clinical Need

Osteonecrosis is a serious complication of antileukemic therapy associated with severe pain and reduced mobility, ultimately leading to joint destruction and significant long-term morbidity. The 5-year cumulative incidence of osteonecrosis ranges from 11% to 20% in adolescents and young adults to 3% to 8% in patients aged 30 years and older. Most symptomatic patients have multiple joints affected, which in turn poses a risk factor for developing severe osteonecrosis. Osteonecrosis has a multifactorial genesis. Treatment-associated risk factors for developing osteonecrosis depend on the therapeutic context including the use of glucocorticosteroids and the simultaneous and/or intensified use of asparaginase (ASP) which may, among others, exert its effect on blood supply to the bone through hypertriglyceridemia, hypercholesterolemia, and hypertension. Allogeneic hematopoietic stem cell transplantation, bloodstream infections, and genetic factors may additionally impact the risk of osteonecrosis. In this article, the authors used the best available evidence in the literature to develop management recommendations for the use in the context of steroid and asparaginase containing regimens. These considerations may be helpful for similar treatment approaches.