Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood

Abstract

Corticosteroid can induce osteonecrosis in children with leukemia. Few studies have been designed to assess the influence of a wide range of cumulative steroid dose on this side effect. Prevalence, risk factors of symptomatic osteonecrosis and its impact on adults' Quality of Life were assessed in 943 patients enrolled in the French "Leucémies de l'Enfant et de l'Adolescent" (LEA) cohort of childhood leukemia survivors. During each medical visit, data on previous osteonecrosis diagnosis were retrospectively collected. Patients without a history but with suggestive symptoms were investigated with magnetic resonance imaging. The total steroid dose in equivalent of prednisone was calculated for each patient and its effect on osteonecrosis occurrence was studied in multivariate models. Cumulative incidence was 1.4% after chemotherapy alone versus 6.8% after transplantation (P<0.001). A higher cumulative steroid dose, age over ten years at diagnosis, and treatment with transplantation significantly increased the risk of osteonecrosis. A higher post-transplant steroid dose and age over ten years at time of transplantation were significant factors in the transplanted group. With patients grouped according to steroid dose quartile, cumulative incidence of osteonecrosis reached 3.8% in the chemotherapy group for a dose beyond 5835 mg/m(2) and 23.8% after transplantation for a post-transplant dose higher than 2055 mg/m(2). Mean physical composite score of Quality of Life was 44.3 in patients with osteonecrosis versus 54.8% in patients without (P<0.001). We conclude that total and post-transplant cumulative steroid dose may predict the risk of osteonecrosis, a rare late effect with a strong negative impact on physical domains of Quality of Life.

Figure 1.

Cumulative incidence of osteonecrosis (A) All patients (B) Chemotherapy group versus HSCT group (C). All patients grouped according to cumulative steroid dose quartiles. (D) Chemotherapy patients grouped according to cumulative steroid dose quartiles. (E) HSCT patients grouped according to the post-transplant cumulative steroid dose quartiles. Almost all patients in the quartile 1 and 2 did not receive any post-transplant steroid therapy. Consequently the first category includes all patients with a cumulative dose equal to 0.