Hip Osteonecrosis in Pediatric Leukemia/Lymphoma Patients Treated with Glucocorticoids: Retrospective Analysis in a Single Institute

Introduction

Because the survival rate of patients with pediatric lymphoblastic leukemia (ALL) has improved in the last five decades, more emphasis has been placed on reducing the adverse side effects of its treatment without compromising on the rate of recovery or chance of survival. Glucocorticoid-induced osteonecrosis (ON) is one of the late complications of ALL treatments, affecting the patients' quality of life. Previous reports indicate that it occurs in up to 50% of children treated for pediatric ALL/lymphoblastic lymphoma (LBL). Joints generally collapse within 2 years of ON identification when it affects more than 30% of the epiphyseal surface, defined herein as extensive ON. Kaste et al. reported the utility of early screening magnetic resonance imaging (MRI) for detecting extensive hip ON and demonstrated its high incidence in patients older than 10 years (J Clin Oncol 33:610-615, 2015). However, there are very few data from Asian studies validating the same. Thus, in this study, we investigated the incidence of hip ON in ALL patients at a single institution in Japan.

Methods

We retrospectively analyzed the rate of incidence of hip ON in Japanease pediatric ALL/LBL patients who were treated with glucocorticoids from January 2003 to May 2017 at our institution. We performed hip MRI screenings at the beginning of maintenance therapy. In patients with radiological ON detected by MRI screening, a follow-up MRI was performed at the end of the maintenance therapy. Overall, 158 patients underwent hip MRI screening at the beginning of the maintenance chemotherapy. The study group comprised 84 males and 74 females, and the median age at diagnosis was 6.5 years (range: 1-22 years).

Results

At the beginning of the maintenance chemotherapy, asymptomatic hip ON, which was detected by MRI screening, was identified in 10 patients (6.3%), and symptomatic hip ON was identified in 1 patient (0.6%)-a 13-year-old girl with T-cell-ALL. Only 1 of 113 (1%) children who were 10 years or younger had ON, whereas 10 of 45 (23.2%) children who were older than 10 years had ON, and there was a statistical difference between these 2 groups (p = 1.38 × 10^-5). There was no statistical difference based on dexamethasone treatment or gender. Of the 10 patients with asymptomatic hip ON, 3 patients (27%) had lesions defined as extensive hip ON. All 10 patients were only observed during the maintenance therapy without special orthopedic management, and a follow-up MRI indicated disease progression in 2 patients. The necrotic lesion remained stable in 4 patients, whereas it improved or completely disappeared in 4 others. Of the 4 patients with stable lesions, 2 patients experienced pain after completion of the maintenance chemotherapy. Although the condition of the patient with symptomatic ON was managed with non-weight bearing therapy, the symptoms worsened and hip joint replacement has now been suggested for this patient.

Conclusions

As reported previously, the incidence of asymptomatic hip ON in patients older than 10 years is considerably high. The incidence of hip symptomatic ON in Japanese children and adolescents older than 10 years was lower the incidence reported previously in other populations [ J Clin Oncol 33:610-615, 2015]. Germline genetic basis might have relationship to ON. To further investigate the change of asymptomatic ON to symptomatic ON, nationwide longer follow-up studies are needed.