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Skeletal abnormalities detected by SPECT is associated with increased relapse risk in pediatric acute lymphoblastic leukemia.

ABSTRACT: Most children with acute lymphoblastic leukemia (ALL) exhibit skeletal abnormalities. This study aimed to investigate bone lesions detected by whole-body bone single-photon emission computed tomography (SPECT) and its prognostic value in children with ALL.A retrospective analysis was performed using whole-body bone SPECT scans obtained from children with ALL in our department between June 2008 and June 2012. A total of 166 children newly diagnosed with ALL were included, and the patients were divided into two groups: patients with positive and negative SPECT scans. We compared the clinical characteristics of the two groups and analyzed the relationship between the skeletal abnormalities detected by SPECT and prognosis.Among the 166 patients, bone scintigraphic abnormalities was detected by SPECT scan in sixty-four patients (38.6%). The most common site was the limbs. There were no significant differences in age, gender, WBC count at diagnosis, risk group and minimal residual disease (MRD) level between SPECT-positive patients and their SPECT-negative counterparts. The event-free and overall survival rates were higher in SPECT-positive patients, but the difference was not statistically significant. However, patients with positive SPECT scans, especially those with multifocal abnormalities (?3 sites), had a higher rate of relapse (P < 0.05). Multivariate analyses identified that abnormal SPECT scan (HR = 3.547, P = 0.015) was an independent relapse risk.Children with ALL and multiple skeletal abnormalities will suffer from relapse. Abnormal SPECT scan was associated with increased relapse risk which might be a potential relapse marker for ALL children.

SUBMITTER: Zhou F

PROVIDER: S-EPMC5668046 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Skeletal abnormalities detected by SPECT is associated with increased relapse risk in pediatric acute lymphoblastic leukemia.

Zhou Fen F Zhang Meiling M Han Juan J Hao Jinjin J Xiao Yan Y Liu Qin Q Jin Runming R Mei Heng H

Oncotarget 20170523 45

<h4>Objectives</h4>Most children with acute lymphoblastic leukemia (ALL) exhibit skeletal abnormalities. This study aimed to investigate bone lesions detected by whole-body bone single-photon emission computed tomography (SPECT) and its prognostic value in children with ALL.<h4>Methods</h4>A retrospective analysis was performed using whole-body bone SPECT scans obtained from children with ALL in our department between June 2008 and June 2012. A total of 166 children newly diagnosed with ALL were ...[more]

PMID: 29108313

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Project description:BACKGROUND:Nucleotide Excision Repair (NER) is a major pathway of mammalian DNA repair that is associated with drug resistance and has not been well characterized in acute lymphoblastic leukemia (ALL). The objective of this study was to explore the role of NER in relapsed ALL patients. We hypothesized that increased expression of NER genes was associated with drug resistance and relapse in ALL. METHODS:We performed secondary data analysis on two sets of pediatric ALL patients that all ultimately relapsed, and who had matched diagnosis-relapse gene expression microarray data (GSE28460 and GSE18497). GSE28460 included 49 precursor-B-ALL patients, and GSE18497 included 27 precursor-B-ALL and 14 T-ALL patients. Microarray data were processed using the Plier 16 algorithm and the 20 canonical NER genes were extracted. Comparisons were made between time of diagnosis and relapse, and between early and late relapsing subgroups. The Chi-square test was used to evaluate whether NER gene expression was altered at the level of the entire pathway and individual gene expression was compared using t-tests. RESULTS:We found that gene expression of the NER pathway was significantly increased upon relapse in patients that took 3 years or greater to relapse (late relapsers, P?=?.007), whereas no such change was evident in patients that relapsed in less than 3 years (early relapsers, P?= .180). Moreover, at diagnosis, the NER gene expression of the early relapsing subpopulation was already significantly elevated over that of the late relapsing group (P?<?.001). This pattern was validated by an 'NER score' established by averaging the relative expression of the 20 canonical NER genes. The NER score at diagnosis was found to be significantly associated with disease-free survival in precursor-B-ALL (P <?.001). CONCLUSION:Patients are over two times more likely to undergo early relapse if they have a high NER score at diagnosis, hazard ratio 2.008, 95% CI (1.256-3.211). The NER score may provide a underlying mechanism for "time to remission", a known prognostic factor in ALL, and a rationale for differential treatment.

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Skeletal abnormalities detected by SPECT is associated with increased relapse risk in pediatric acute lymphoblastic leukemia.

Publications

Skeletal abnormalities detected by SPECT is associated with increased relapse risk in pediatric acute lymphoblastic leukemia.

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