British OsteoNEcrosis Study (BONES) protocol: a prospective cohort study to examine the natural history of osteonecrosis in older children, teenagers and young adults with acute lymphoblastic leukaemia and lymphoblastic lymphoma

Abstract

Introduction: Osteonecrosis is a well-recognised treatment-related morbidity risk in patients diagnosed with acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL), with a high rate of affected patients requiring surgical intervention. Patients may have asymptomatic changes on imaging studies that spontaneously regress, and little is known about the natural history of osteonecrotic changes seen. The main aim of the British OsteoNEcrosis Study (BONES) is to determine the incidence of symptomatic and asymptomatic osteonecrosis in the lower extremities of survivors of ALL or LBL diagnosed aged 10-24 years in the UK at different time points in their treatment. This study also aims to identify risk factors for progression and the development of symptomatic osteonecrosis in this population, as well as specific radiological features that predict for progression or regression in those with asymptomatic osteonecrosis METHODS AND ANALYSIS: BONES is a prospective, longitudinal cohort study based at principal treatment centres around the UK. Participants are patients aged 10-24 years diagnosed with ALL or LBL under standard criteria. Assessment for osteonecrosis will be within 4 weeks of diagnosis, at the end of delayed intensification and 1, 2 and 3 years after the start of maintenance therapy. Assessment will consist of MRI scans of the lower limbs and physiotherapy assessment. Clinical and biochemical data will be collected at each of the time points. Bone mineral density data and vertebral fracture assessment using dual-energy X-ray absorptiometry will be collected at diagnosis and annually for 3 years after diagnosis of malignancy.

Ethics and dissemination: Ethical approval has been obtained through the Yorkshire and Humber Sheffield Research Ethics Committee (reference number: 16/YH/0206). Study results will be published on the study website, in peer-reviewed journals and presented at relevant conferences and via social media.

Trial registration number: NCT02598401; Pre-results.

Keywords: leukaemia; lymphoma; paediatrics.

Figure 1

UKALL 2011 trial schema for patients over the age of 10 (excluding patients with Down’s syndrome). BCP, B-cell precursor; BFM, Berlin-Frankfurt-Munich; LBL, lymphoblastic lymphoma; MRD, minimal residual disease; RER, rapid early response (<25% blasts at day 8 of induction); SER: slow early response (≥25% blasts at day 8 of induction).

Figure 2

Schema of BONES study procedures. BONES, British OsteoNEcrosis Study; CHAQ, Childhood Health Assessment Questionnaire; DXA, dual-energy X-ray absorptiometry; LFTs, liver function tests; LDL, low-density lipoprotein; HDL, high-density lipoprotein.