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Bone marrow oedema predicts bone collapse in paediatric and adolescent leukaemia patients with corticosteroid-induced osteonecrosis.

ABSTRACT: OBJECTIVES:Corticosteroid treatment of paediatric leukaemia patients can lead to osteonecrosis (ON). We determined whether bone marrow oedema (BME) is an early sign of progressive ON and eventual bone collapse. METHODS:In a retrospective study, two radiologists reviewed MR imaging characteristics of 47 early stage epiphyseal ON in 15 paediatric and adolescent leukaemia patients. Associations between BME on initial imaging studies and subchondral fracture, disease progression and bone collapse were assessed by Cochran-Mantel-Haenszel tests. Differences in time to progression and bone collapse between lesions with and without oedema were assessed by log rank tests. RESULTS:Forty-seven occurrences of ON were located in weight bearing joints, with 77% occurring in the femur. Seventeen lesions progressed to collapse, two lesions worsened without collapse, and 28 remained stable or improved. BME was significantly associated with subchondral fracture (p?=?0.0014), disease progression (p?=?0.0015), and bone collapse (p?

SUBMITTER: Theruvath AJ

PROVIDER: S-EPMC5718952 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Bone marrow oedema predicts bone collapse in paediatric and adolescent leukaemia patients with corticosteroid-induced osteonecrosis.

Theruvath Ashok Joseph AJ Sukerkar Preeti Arun PA Bao Shanshan S Rosenberg Jarrett J Luna-Fineman Sandra S Kharbanda Sandhya S Daldrup-Link Heike Elisabeth HE

European radiology 20170719 1

<h4>Objectives</h4>Corticosteroid treatment of paediatric leukaemia patients can lead to osteonecrosis (ON). We determined whether bone marrow oedema (BME) is an early sign of progressive ON and eventual bone collapse.<h4>Methods</h4>In a retrospective study, two radiologists reviewed MR imaging characteristics of 47 early stage epiphyseal ON in 15 paediatric and adolescent leukaemia patients. Associations between BME on initial imaging studies and subchondral fracture, disease progression and b ...[more]

PMID: 28726121

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Project description:ObjectiveTo demonstrate proof-of-concept for a quantitative MRI method using histographic analysis to assess bone marrow oedema and fat metaplasia in the sacroiliac joints.Materials and methodsFifty-three adolescents aged 12-23 with known or suspected sacroiliitis were prospectively recruited and underwent quantitative MRI (qMRI) scans, consisting of chemical shift-encoded (at 3 T) and diffusion-weighted imaging (at 1.5 T), plus conventional MRI (at 1.5 T) and clinical assessment. qMRI scans produced proton-density fat fraction (PDFF) and apparent diffusion coefficient (ADC) maps of the sacroiliac joints (SIJs), which were analysed using an in-house software tool enabling partially automated ROI definition and histographic analysis. Logistic regression and receiver operating characteristic (ROC) analyses assessed the predictive performance of ADC- and PDFF-based parameters in identifying active inflammation (oedema) and structural damage (fat metaplasia).ResultsADC-based parameters were associated with increased odds of oedema (all p < 0.05); ROC-AUC was higher for histographic parameters representing the upper end of the ADC distribution than for simple averages. Similarly, PDFF-based parameters were associated with increased odds of fat metaplasia (all p < 0.05); ROC area-under-the-curve was higher for histographic parameters representing the upper end of the PDFF distribution than for simple averages. Both ADC- and PDFF-based histographic parameters demonstrated excellent inter- and intra-observer agreement (ICC > 0.9).ConclusionsADC-based parameters can differentiate patients with bone marrow oedema from those without, whilst PDFF-based parameters can differentiate patients with fat metaplasia from those without. Histographic analysis might improve performance compared with simple averages such as the mean and median and offers excellent agreement within and between observers.Key points• Quantitative MRI with histographic analysis can identify bone marrow oedema (an active inflammatory lesion) and fat metaplasia (a 'chronic' inflammatory lesion) in patients with spondyloarthritis. • The use of histographic analysis might improve the performance of quantitative MRI for detecting bone marrow oedema and fat metaplasia compared with simple averages such as the mean and median. • Bone marrow oedema and fat metaplasia are known to be of diagnostic and prognostic significance, and the proposed method could support clinical decisions around biologic (and other) therapies in spondyloarthritis.

Project description:It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance. We observed highly dynamic cellular interactions and promiscuous distribution of leukaemia cells that migrated across the bone marrow, without showing any preferential association with bone marrow sub-compartments. Unexpectedly, this behaviour was maintained throughout disease development, from the earliest bone marrow seeding to response and resistance to chemotherapy. Our results reveal that T-ALL cells do not depend on specific bone marrow microenvironments for propagation of disease, nor for the selection of chemo-resistant clones, suggesting that a stochastic mechanism underlies these processes. Yet, although T-ALL infiltration and progression are independent of the stroma, accumulated disease burden leads to rapid, selective remodelling of the endosteal space, resulting in a complete loss of mature osteoblastic cells while perivascular cells are maintained. This outcome leads to a shift in the balance of endogenous bone marrow stroma, towards a composition associated with less efficient haematopoietic stem cell function. This novel, dynamic analysis of T-ALL interactions with the bone marrow microenvironment in vivo, supported by evidence from human T-ALL samples, highlights that future therapeutic interventions should target the migration and promiscuous interactions of cancer cells with the surrounding microenvironment, rather than specific bone marrow stroma, to combat the invasion by and survival of chemo-resistant T-ALL cells.

Dataset Information

Bone marrow oedema predicts bone collapse in paediatric and adolescent leukaemia patients with corticosteroid-induced osteonecrosis.

Publications

Bone marrow oedema predicts bone collapse in paediatric and adolescent leukaemia patients with corticosteroid-induced osteonecrosis.

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