Folate Homeostasis in Cerebrospinal Fluid During Therapy for Acute Lymphoblastic Leukemia

Peter D. Cole, Katherine A. Beckwith, Veena Vijayanathan, Sudipta Roychowdhury, Angela K. Smith, Barton A. Kamen

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The neurotoxic effects of therapy for childhood acute lymphoblastic leukemia can result in leukoencephalopathy or measurable deficits in cognitive function. However, there are no validated biomarkers that allow the identification of those patients at greatest risk. With the objective of identifying such predictors, cerebrospinal fluid collected from 53 patients over 2.5 years of therapy for childhood acute lymphoblastic leukemia was retrospectively studied. Cerebrospinal fluid folate, concentrated relative to serum folate prior to therapy, dropped during the first month of therapy and remained below baseline throughout treatment. Cerebrospinal fluid homocysteine was inversely related to cognitive function prior to treatment. Oral methotrexate was associated with decreased cerebrospinal fluid folate and increased cerebrospinal fluid homocysteine, but these changes were not seen with oral aminopterin. Of 36 patients who had imaging after completion of therapy, 9 had periventricular or subcortical white matter abnormalities consistent with leukoencephalopathy. Peak cerebrospinal fluid tau concentrations during therapy were higher among patients who had leukoencephalopathy after completion of therapy than among those with normal imaging studies at the end of therapy. If confirmed prospectively, these markers may allow the identification of those patients at greatest risk of developing treatment-induced neurocognitive dysfunction, thus guiding preventive interventions.

Original languageEnglish (US)
Pages (from-to)34-41
Number of pages8
JournalPediatric Neurology
Volume40
Issue number1
DOIs
StatePublished - Jan 2009

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Fluid Therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Folic Acid
Cerebrospinal Fluid
Homeostasis
Leukoencephalopathies
Therapeutics
Homocysteine
Cognition
Aminopterin
Methotrexate
Biomarkers

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Cite this

Cole, P. D., Beckwith, K. A., Vijayanathan, V., Roychowdhury, S., Smith, A. K., & Kamen, B. A. (2009). Folate Homeostasis in Cerebrospinal Fluid During Therapy for Acute Lymphoblastic Leukemia. Pediatric Neurology, 40(1), 34-41. https://doi.org/10.1016/j.pediatrneurol.2008.09.005

Folate Homeostasis in Cerebrospinal Fluid During Therapy for Acute Lymphoblastic Leukemia. / Cole, Peter D.; Beckwith, Katherine A.; Vijayanathan, Veena; Roychowdhury, Sudipta; Smith, Angela K.; Kamen, Barton A.

In: Pediatric Neurology, Vol. 40, No. 1, 01.2009, p. 34-41.

Research output: Contribution to journalArticle

Cole, PD, Beckwith, KA, Vijayanathan, V, Roychowdhury, S, Smith, AK & Kamen, BA 2009, 'Folate Homeostasis in Cerebrospinal Fluid During Therapy for Acute Lymphoblastic Leukemia', Pediatric Neurology, vol. 40, no. 1, pp. 34-41. https://doi.org/10.1016/j.pediatrneurol.2008.09.005
Cole, Peter D. ; Beckwith, Katherine A. ; Vijayanathan, Veena ; Roychowdhury, Sudipta ; Smith, Angela K. ; Kamen, Barton A. / Folate Homeostasis in Cerebrospinal Fluid During Therapy for Acute Lymphoblastic Leukemia. In: Pediatric Neurology. 2009 ; Vol. 40, No. 1. pp. 34-41.
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