Structural and Functional Brain Imaging in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia Treated With Chemotherapy: A Systematic Review

Abstract

Background The effect of chemotherapy on brain development in long-term survivors of pediatric acute lymphoblastic leukemia (ALL) was systematically reviewed. Methods A systematic search of Pubmed, Scopus, and PsycINFO databases was conducted to identify articles published between January 2000 and February 2020 that implemented magnetic resonance imaging to assess brain structure and function in pediatric ALL survivors (diagnosed < 21 years of age). The review included articles that were published on children diagnosed with ALL between 0–21 years of age and treated with chemotherapy-only protocols. Articles meeting the inclusion criteria described survivors on average ≥ 5 years from diagnosis, were peer-reviewed articles, and original studies. Results The search yielded 1,975 articles with 23 articles meeting inclusion criteria. The review revealed that survivors had statistically significant alterations in brain anatomy, most commonly a smaller hippocampus and impaired microstructural white matter integrity in frontal brain regions. Survivors also had impaired brain function including lower brain network efficiency and altered resting state connectivity. Survivors also displayed wide-spread reductions in brain activation (ie, frontal, temporal, parietal brain regions) during cognitive tasks. Conclusion While the neurotoxic effects of cancer treatment are reduced in the absence of cranial radiation, survivors treated on chemotherapy-only protocols still display long-term alterations in brain structure and function which contribute to life-long neurocognitive late-effects.

Motor Functioning and Intelligence Quotient in Paediatric Survivors of a Fossa Posterior Tumor Following a Multidisciplinary Rehabilitation Program

“…Of course, although extremely interesting, a comparative age-matched study with fossa posterior tumor survivors who did not receive rehabilitation is not possible in our hospital due to ethical reasons. Chemotherapy and radiotherapy have a known suppressive effect on brain plasticity, cognitive development and physical performance [ 34 , 39 , 40 , 41 ]. Therefore, the primary goal of early rehabilitation is to try to (partially) counteract serious decline in physical and cognitive skills, and to prevent secondary complications [ 42 ].…”

Cranial MRI in Childhood Acute Leukemia during Treatment and Follow-Up Including the Impact of Intrathecal MTX—A Single-Center Study and Review of the Literature

“…The risk of developing neurocognitive impairments during long-term follow-up in children with acute leukemias is well known, and not only in those children receiving cranial irradiation [8]. The main cause is treatment with potential neurotoxic drugs during the vulnerable phase of brain maturation [38][39][40].…”

“…The main cause is treatment with potential neurotoxic drugs during the vulnerable phase of brain maturation [38][39][40]. The literature can be divided into two groups, firstly about morphologic changes of the brain in children treated for acute leukemias alone [15][16][17][18][19][20][21][22][23][24][25][26][27][28]41,42] and secondly about the association between cMRI alterations and neurocognitive sequelae [2][3][4][5][6][7][8][9][10][11][12][13]22,34,[43][44][45][46].…”

“…MTX. Gandy et al [8] reviewed 23 articles dealing with brain imaging of ALL survivors and stated that even i.v. chemotherapy can have neurotoxic sequelae by damaging the blood-brain barrier (BBB), inducing the apoptosis of brain cells, directly harming DNA, increasing oxidative stress, shortening the telomere length, and impairing neurogenesis.…”

“…Besides the effectiveness of the current treatments, short-and long-term sequelae need to be taken seriously. Deterioration of neurocognitive function is one of the most relevant late effects [2][3][4][5][6][7][8][9][10][11][12][13]. To analyze the reason for declined neurocognitive abilities, imaging studies of the central nervous system (CNS) are helpful Cancers 2022, 14, 4688 2 of 16 to find correlated morphological changes.…”