Abstract Details

Title Intrathecal Chemotherapy-Associated Vasospasm in Children with Leukemia

Topic Child Neurology and Developmental Neurology

Presentation(s) S38 - Child Neurology and Developmental Neurology: Acquired Brain Injury: Brain-Behavior Relationships (1:36 PM-1:48 PM)

Poster/Presentation
Number 004

Objective

To evaluate frequency of and risk factors for subclinical cerebral vasospasm associated with intrathecal (IT) chemotherapy in children with hematologic malignancies.

Background Cytarabine, which is commonly administered intrathecally during induction chemotherapy for childhood hematologic malignancies, has well-documented but poorly understood neurotoxicity. Recent reports suggest a role for cerebrovascular dysfunction in the pathogenesis of cytarabine toxicity. We hypothesized that a subgroup of children receiving IT cytarabine develop subclinical vasospasm, which may contribute to long-term neurocognitive sequelae of childhood cancer.

Design/Methods

In this prospective self-controlled case series, we enrolled participants <26 years old receiving IT cytarabine for newly diagnosed leukemia or lymphoma. We measured cerebral blood flow velocities (CBFVs) using transcranial Doppler ultrasound at baseline (pre-treatment) and at 1, 4, and 8 days after IT cytarabine. The primary outcome was change in CBFVs of the middle cerebral arteries (MCAs). Demographic, laboratory, medication, and clinical data were collected.

Results Eighteen participants, ages 2-23 years, completed the study. All subjects had elevated baseline CBFVs compared to age-based normative data. After cytarabine, 4 subjects (22%) met criteria for vasospasm, with increases in peak MCA CBFVs of 34-45% (35.5-44.5 cm/s). When available, Lindegaard ratios confirmed vasospasm (LI>3). Children with AML were more likely to develop vasospasm compared to children with other malignancy types (p=0.0006). There were no significant differences in age, sex, race, ethnicity, baseline CBFVs, cytarabine dose, hematocrit, or change in hematocrit from baseline between the vasospasm and non-vasospasm groups.

Conclusions In this preliminary study, we identified distinct patterns of cerebral blood flow in children undergoing induction chemotherapy for hematologic malignancies, and we identified AML as a risk factor for subclinical vasospasm. Future research is needed to determine if subclinical vasospasm is a harbinger of neurologic sequelae in this population, and if so, to focus on prevention of these complications.

Authors/Disclosures
Lisa Sun, MD PRESENTER	Dr. Sun has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for multiple law firms. The institution of Dr. Sun has received research support from American Heart Association. The institution of Dr. Sun has received research support from Thrasher Research Fund. The institution of Dr. Sun has received research support from Laney Jaymes Foundation for Pediatric Stroke.
Patrick C. Brown	No disclosure on file
Rebecca F. Gottesman, MD (Johns Hopkins University)	The institution of Dr. Gottesman has received research support from NIH.
	No disclosure on file
Wendy C. Ziai, MD (Johns Hopkins Univ, Neuro Critical Care)	Dr. Ziai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lumosa. Dr. Ziai has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bard. Dr. Ziai has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Ziai has received research support from NIH. Dr. Ziai has received publishing royalties from a publication relating to health care. Dr. Ziai has received personal compensation in the range of $500-$4,999 for serving as a Consultant with DOJ.
Ryan Felling, MD (Johns Hopkins University)	No disclosure on file

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