Research reportStructural brain alteration in survivors of acute lymphoblastic leukemia with chemotherapy treatment: A voxel-based morphometry and diffusion tensor imaging study
Introduction
Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children, accounting for 74% of all leukemia and 18% of all cancers (Kanellopoulos et al., 2016). The historical treatment of cranial radiation therapy (CRT) has result in a 5 year event-free survival rate of approximately 80% in standard risk ALL after intensive chemotherapy treatment of the central nervous system (Cheung and Krull, 2015, Gaynon et al., 2010). However, it is also reported that ALL survivors suffer from long-term neurocognitive impairment, and it has a negative impact on their health related quality of life (QoL) (Huang et al., 2013). Possible mechanisms for cognitive impairment include direct neurotoxic effects causing atrophy of grey matter (GM) and/or demyelination of the white matter (WM), secondary immunologic responses leading to inflammatory reactions and microvascular damage (Saykin et al., 2003, Seigers and Fardell, 2011).
Neuroimaging may provide insights to anatomic substrates of potential toxic treatment effects. Previous studies using conventional magnetic resonance imaging (MRI) (Ashford et al., 2010, Krappmann et al., 2007, Reddick et al., 2014), functional MRI (Kesler et al., 2014, Luxton et al., 2014, Robinson et al., 2010), and diffusion tensor imaging (Edelmann et al., 2013, Schuitema et al., 2013) has enhanced our understanding of possible underlying pathophysiologic mechanisms.
Voxel-based morphometry (VBM) is an automated technique for evaluating brain structures, which requires no a priori regional assumptions. Compared to VBM, DTI provides information on the WM integrity by measuring the motion of water molecules (Tu et al., 2016). Tract-based spatial statistics (TBSS) analysis has been used for assessing WM integrity by fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) (Smith et al., 2006). Generally, decreased FA means demyelination, axonal loss and inflammation. AD refers to identify axonal damage or degeneration, whereas RD shows myelin injury selectively (Assaf and Pasternak, 2008).
In the present study, we sought to characterize possible brain changes in ALL patients with chemotherapy treatment by combining VBM and TBSS methods. In this approach, we wanted to assess whether GM and WM alterations in ALL patients.
Section snippets
Participants
Between June 2015 and June 2016, 32 ALL patients who had completed all anti-cancer treatment with chemotherapy treatment in Second hospital of Anhui Medical University were recruited. Four of the 32 survivors withdrew during data collection, leaving 28 participants (mean age: 40.71 ± 8.58 years, years since diagnosis: 7–38) were included. Systemic chemotherapy included prednisolone, vincristine, cyclophosphamide, daunorubicin, doxorubicin, asparaginase, teniposide, cytarabine, 6-mercaptopurine,
Results
There was no significant difference for age and gender between the ALL patients and healthy controls (p > 0.05, Table 1).
Discussion
In the present study, we found a alteration in GM volume and a widespread changes in WM microstructural (decreased FA and AD, increase in MD and RD) in ALL patients when compared to healthy controls.
For GM changes in ALL patients, our study demonstrated that decreased GM volumes occurred in several brain areas of ALL patients with chemotherapy treatment, which indicated that cortical atrophy occurs in ALL patients with chemotherapy treatment. Compared to healthy controls, the ALL groups have
Acknowledgements
This work was supported by Anhui Provincial Public Linkage Projects (1604f0804025), Anhui Provincial General Medicine Clinical Scientific Projects (2016QK089) and Anhui Provincial Quality Projects (2014jxtd119).
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