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Bony Morbidity in Children Treated for Acute Lymphoblastic Leukemia

From the Department of Pediatrics, Massachusetts General Hospital; Quality Control Center and Departments of Pediatric Oncology and Biostatistical Science, Dana-Farber Cancer Institute; and Division of Hematology/Oncology, Children’s Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA.

Address reprint requests to Lewis B. Silverman, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email: lewis_ silverman{at}dfci.harvard.edu

PURPOSE: Corticosteroids are widely used in the treatment of acute lymphoblastic leukemia (ALL). To determine the frequency of corticosteroid-associated bony morbidity in children with ALL, we retrospectively evaluated the incidence of fractures and osteonecrosis (ON) on two consecutive pediatric ALL protocols.

PATIENTS AND METHODS: One hundred seventy-six consecutive children were treated for ALL between 1987 and 1995 at the Dana-Farber Cancer Institute and Children’s Hospital. Prednisone was used as the corticosteroid during postremission therapy from 1987 to 1991, and dexamethasone was used from 1991 to 1995. Medical records for all patients were reviewed to assess the occurrence of fractures and ON.

RESULTS: With a median follow-up of 7.6 years, the 5-year cumulative incidence (CI) ± SE of any bony morbidity for the 176 patients was 30% ± 4%, with a 5-year CI of fractures of 28% ± 3% and of ON of 7% ± 2%. With multivariate analysis, independent predictors of bony morbidity included age 9 to 18 years at diagnosis (P < .01), male sex (P < .01), and treatment with dexamethasone (P = .01). Dexamethasone was associated with a higher risk of fractures (5-year CI, 36% ± 5% v 20% ± 4% with prednisone; P = .04), but not ON (P = .40). The 5-year event-free survival for the 176 patients was 79% ± 3%.

CONCLUSION: Children treated for ALL had a high incidence of fractures and ON. Older children, boys, and patients receiving dexamethasone were at increased risk for the development of bony morbidity. Future studies should attempt to minimize corticosteroid-associated bony morbidity without compromising clinical efficacy.

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