Abstract
Background
Mechanisms of chemotherapy-associated neurotoxicity are poorly understood, and therefore, prevention strategies have not been developed. We hypothesized that a subgroup of children receiving intrathecal cytarabine develops subclinical vasospasm, which may contribute to long-term neurocognitive sequelae of cancer.
Methods
We used transcranial Doppler ultrasound to serially evaluate cerebral blood flow velocities in participants ≤25 years old receiving intrathecal cytarabine for hematologic malignancies.
Results
Four of 18 participants (22%) met the criteria for subclinical vasospasm within 4 days of intrathecal cytarabine administration. The distribution of oncologic diagnoses differed between the vasospasm and non-vasospasm groups (p = 0.02). Acute myeloid leukemia was identified as a potential risk factor for vasospasm. Children with vasospasm were more likely to have received intravenous cytarabine (75% versus 0%, p = 0.01) and less likely to have received steroids (25% versus 100%, p = 0.01).
Conclusions
A subpopulation of children with hematologic malignancies develops subclinical vasospasm after intrathecal cytarabine treatment. Future research is needed to determine the long-term clinical consequences of cerebral vasospasm in this population.
Impact
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A subset of children with hematologic malignancies who receive intrathecal cytarabine experience subclinical cerebral vasospasm, as measured by transcranial Doppler ultrasound.
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Of children receiving intrathecal cytarabine, those who develop cerebral vasospasm are more likely to have diagnosis of acute myeloid leukemia, more likely to receive concurrent intravenous cytarabine, and less likely to receive steroids as part of their chemotherapy regimen, as compared with children without vasospasm.
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Future research is needed to determine if vasospasm during chemotherapy is associated with higher rates of neurocognitive dysfunction, and if so, to focus on prevention of these long-term sequelae of childhood cancer.
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Acknowledgements
The authors would like to thank Bobby Ergin and Vladimir Ponomarev for their technical assistance. This study was funded by the Thrasher Research Fund.
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L.R.S. conceived of and designed the study. L.R.S., W.Z., P.B., and A.G.T. acquired the data. L.R.S., W.Z., P.B., S.C., R.F.G., and R.J.F. analyzed and interpreted the data. L.R.S. drafted the manuscript. L.R.S., W.Z., P.B., R.F.G., and R.J.F. critically revised the manuscript of important intellectual content. L.R.S., W.Z., P.B., A.G.T., S.C., R.F.G., and R.J.F. approved of the final version to be published.
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R.F.G. is an associate editor for Neurology; otherwise, we have no relevant conflicts of interest or disclosures to report.
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This study was approved by the institutional review board. All families signed informed consent, and all children 7 years of age or older gave verbal assent.
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Sun, L.R., Ziai, W., Brown, P. et al. Intrathecal chemotherapy-associated cerebral vasospasm in children with hematologic malignancies. Pediatr Res 89, 858–862 (2021). https://doi.org/10.1038/s41390-020-1008-1
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DOI: https://doi.org/10.1038/s41390-020-1008-1
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