Neuropsychological, Neuroanatomical, and Neurophysiological Consequences of CNS Chemotherapy for Acute Lymphoblastic Leukemia

Abstract

Medical treatment for acute lymphoblastic leukemia (ALL) has improved survival rates to 70% for children currently diagnosed with this disease. Intrathecal (IT) chemotherapy replaced CNS radiation therapy (CRT) for those with a favorable diagnosis as research revealed cognitive deficits associated with CRT. The literature pertaining to the potential adverse intellectual and neurophysiological consequences of IT chemotherapy is reviewed. It is concluded that IT chemotherapy may not be a benign form of treatment, although its effects may be more subtle than those produced by CRT. Future studies implementing more comprehensive test batteries are needed to illuminate these deficits so that remediation may be possible for ALL survivors.

Late Effects of Childhood Leukemia Therapy

“…One meta-analysis of 13 small studies reported a significant difference in IQ between children treated for ALL versus controls when assessed 4.7 years after treatment [45]. Another review of 33 studies in children with ALL, conducted through 1997, found that two thirds of the studies reported cognitive deficits in survivors treated with chemotherapy alone [62]. However, other studies have not reported such differences 4 to 10 years after diagnosis [64,67,71,72].…”

Neuropsychological Sequelae of Non-Central Nervous System Cancer and Cancer Therapy

“…This subacute process typically occurs within days to weeks after treatment and can involve progressive limb weakness, cranial nerve palsies, seizures, visual disturbance, coma and even death (Moleski 2000). Methotrexate, especially when accompanied by radiation therapy, has also been reported to cause microvascular injury including mineralizing microangiopathy, vasodilation, endothelial damage, and stroke-like leukoencephalopathy (Moleski 2000). Whether this represents ischemic events, demyelination or edema within the cerebral white matter is a matter of ongoing research (Haykin et al 2006;Brown et al 1998).…”

“…Findings have been mixed; however, attention, processing speed, executive function, and nonverbal memory, and problem solving appear to be more vulnerable to adverse effects of chemotherapy. The interested reader is referred to Moore (2005) and Moleski (2000) for a more in-depth review of treatment-related cognitive dysfunction in children.…”

White Matter Fractional Anisotropy Correlates With Speed of Processing and Motor Speed in Young Childhood Cancer Survivors

“…Deficits in attention, memory, and speed of processing are commonly found in survivors (2)(3)(4)(5). Children treated for acute lymphoblastic leukemia (ALL) have also shown treatment-induced neurotoxicity; this is probably caused by intrathecal and/or high-dose intravenous methotrexate (MTX), which is a replacement for cranial radiation therapy as central nervous system (CNS) prophylaxis, although published data are inconsistent (6)(7)(8).…”