MRI morphometric and neuropsychological correlates of long‐term memory in survivors of childhood leukemia

Abstract

Our hypothesis of deficits in both long-term memory and its neural substrates was not supported. It was concluded that the hippocampus, as an early developing structure, may be less vulnerable to chemotherapy treatment. Children surviving ALL are able to retain and retrieve once learned information comparable with peers.

Neurocognitive outcomes in long-term survivors of childhood acute lymphoblastic leukemia treated on contemporary treatment protocols: A systematic review

“…(Von der Weid,2001; Langer et al,2002; Hill et al,2004; Spiegler et al,2006; Mahone et al,2007; Aukema et al,2009; Kadan-Lottick et al,2009; Kadan-Lottick et al,2010; Robinson et al,2010; Daams et al,2012; Krawczuk-Rybak et al,2012; Edelmann et al,2013; Genschaft et al,2013; Krull et al,2013; Lewis et al,2013; Ross et al,2013; Schuitema et al,2013; Edelmann et al,2014; Elalfy et al,2014) There were only 4 longitudinal studies that evaluated survivors’ neurocognitive changes from active treatment to post-treatment survivorship phase. (Kingma et al,2001; Harila et al,2009; Halsey et al,2011; Lewis et al,2013) Most studies focused on a pure sample of survivors who received chemotherapy-only treatment protocols while others included separate populations of ALL survivors who received CRT(Kingma et al,2001; Von der Weid,2001; Langer et al,2002; Spiegler et al,2006; Harila et al,2009; Kadan-Lottick et al,2010; Halsey et al,2011; Krull et al,2011; Daams et al,2012; Krull et al,2013; Schuitema et al,2013; Edelmann et al,2014) or patients of other cancer types.…”

“…(Kingma et al,2001; Harila et al,2009; Halsey et al,2011; Lewis et al,2013) Most studies focused on a pure sample of survivors who received chemotherapy-only treatment protocols while others included separate populations of ALL survivors who received CRT(Kingma et al,2001; Von der Weid,2001; Langer et al,2002; Spiegler et al,2006; Harila et al,2009; Kadan-Lottick et al,2010; Halsey et al,2011; Krull et al,2011; Daams et al,2012; Krull et al,2013; Schuitema et al,2013; Edelmann et al,2014) or patients of other cancer types. (Aukema et al,2009; Kadan-Lottick et al,2010) The majority of the included studies had sample sizes between 10 to 50 subjects,(Kingma et al,2001; Langer et al,2002; Hill et al,2004; Mahone et al,2007; Aukema et al,2009; Harila et al,2009; Daams et al,2012; Krawczuk-Rybak et al,2012; Edelmann et al,2013; Genschaft et al,2013; Schuitema et al,2013; Edelmann et al,2014) with the exception of 4 studies with a larger cohort of more than 100 subjects(Von der Weid,2001; Kadan-Lottick et al,2010; Halsey et al,2011; Krull et al,2013) and 3 studies with less than 10 subjects. (Lewis et al,2012; Lewis et al,2013; Ross et al,2013) Most the studies reported survivors’ mean duration of time since diagnosis, which ranged between 5 and 22 years.…”

“…Eighteen studies included a population of non-cancer controls or a normative healthy sample for comparative purposes. (Kingma et al,2001; Hill et al,2004; Spiegler et al,2006; Mahone et al,2007; Aukema et al,2009; Harila et al,2009; Kadan-Lottick et al,2010; Robinson et al,2010; Halsey et al,2011; Daams et al,2012; Lewis et al,2012; Edelmann et al,2013; Genschaft et al,2013; Krull et al,2013; Lewis et al,2013; Schuitema et al,2013; Edelmann et al,2014; Elalfy et al,2014) All patients in the included studies received customized chemotherapy-only contemporary protocols (referred to as “contemporary protocols” thereafter) that originated from the Berlin-Frankfurt-Münster (BFM) Study Group, Children’s Oncology Group (COG), Dana-Farber Cancer Institute ALL Consortium, Dutch Childhood Leukemia Study Group (DCLSG) and St. Jude Children's Research Hospital (SJCRH). The most commonly administered drugs were vincristine, corticosteroid (hydrocortisone, dexamethasone or prednisone), L-asparaginase, and anthracycline (either doxorubicin or daunorubicin).…”

Neurologic toxicities of cancer therapies

“…Historically, the association of leukoencephalopathy and neurocognitive disturbances has been indeterminate. Child survivors of systemic ALL treated with methotrexate often suffer with intellectual impairment and learning disabilities [53][54][55]. Adults, most often treated with high-dose intravenous methotrexate for primary central nervous system lymphoma, develop a syndrome closely resembling normal pressure hydrocephalus characterized by disturbances of memory, attention, and gait, and urinary incontinence.…”

Acute Lymphoblastic Leukemia: What Have We Learned About the Effects of This Disease and Its Treatment on the Nervous System?

“…Hippocampal dedritic spine damage is found after single-dose administration of cyclophosphamide in hippocampal slices, and causes transient impairment of long-term potentiation (Lee et al, 2006). Clinically, reduced hippocampal volume and loss of neurogenesis have been found in chemotherapy treated colon cancer patients (Schneiderman, 2004) and brain tumor patients 37 , respectively, though no clear changes were found in ALL survivors (Hill et al, 2004). However, the attention and memory deficits present in ALL patients might suggest a functional deficit even if no structural changes are clearly defined.…”