Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia

Introduction Central nervous system (CNS) treatment using intrathecal chemotherapy and cranial radiation to enable long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) comes at the cost of neurotoxic side effects and long-term sequelae. We investigated oxidative stress a...

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Published in:Curēus (Palo Alto, CA) CA), 2021-06, Vol.13 (6), p.e15997
Main Authors: Dewan, Pooja, Chaudhary, Preety, Gomber, Sunil, Ahmed, Rafat S, Kotru, Mrinalini
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Neurology
Oncology
Pediatrics
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Chaudhary, Preety
Gomber, Sunil
Ahmed, Rafat S
Kotru, Mrinalini
description Introduction Central nervous system (CNS) treatment using intrathecal chemotherapy and cranial radiation to enable long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) comes at the cost of neurotoxic side effects and long-term sequelae. We investigated oxidative stress as a possible mechanism of chemotherapy-induced neurotoxicity in children with ALL. Materials and methods In this case-control study, we estimated the cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OH-dG), a DNA damage product, in children with B-cell ALL and control children. CSF samples were collected at diagnosis, at end of Induction 1, Induction 2, and Induction 2A - consolidation phase. CSF 8-OH-dG levels were compared in children with and without neurotoxicity. Results Children with ALL (n=23) at diagnosis had significantly higher median (interquartile range, IQR) CSF 8-OH-dG levels (ng/mL) compared to controls (n=19) [1.97 (1.59-2.56) Vs 0.65 (0.59-0.82), P
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We investigated oxidative stress as a possible mechanism of chemotherapy-induced neurotoxicity in children with ALL. Materials and methods In this case-control study, we estimated the cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OH-dG), a DNA damage product, in children with B-cell ALL and control children. CSF samples were collected at diagnosis, at end of Induction 1, Induction 2, and Induction 2A - consolidation phase. CSF 8-OH-dG levels were compared in children with and without neurotoxicity. Results Children with ALL (n=23) at diagnosis had significantly higher median (interquartile range, IQR) CSF 8-OH-dG levels (ng/mL) compared to controls (n=19) [1.97 (1.59-2.56) Vs 0.65 (0.59-0.82), P&lt;0.001]. CSF 8-OH-dG levels at the end of four weeks, eight weeks, and 16 weeks of chemotherapy were [3.96 (2.85-5.44) ng/mL], 1.00 (0.89-1.09), and 3.73 (2.80-4.39) ng/mL, respectively. Out of 23 children with ALL, 12 developed neurotoxicity; the CSF levels of 8-OH-dG in them were only marginally higher compared to those who did not develop neurotoxicity. The CSF 8-OH-dG levels did not show a significant correlation with the number of doses of methotrexate or vincristine received. Conclusion Chemotherapy increases the CNS oxidative stress as measured by CSF 8-OH-dG levels, with the levels being proportional to the intensity of chemotherapy. Children with neurotoxicity had only marginally higher CSF 8-OH-dG levels as compared to children without neurotoxicity.</description><identifier>ISSN: 2168-8184</identifier><identifier>EISSN: 2168-8184</identifier><identifier>DOI: 10.7759/cureus.15997</identifier><identifier>PMID: 34336488</identifier><language>eng</language><publisher>United States: Cureus</publisher><subject>Neurology ; Oncology ; Pediatrics</subject><ispartof>Curēus (Palo Alto, CA), 2021-06, Vol.13 (6), p.e15997</ispartof><rights>Copyright © 2021, Dewan et al.</rights><rights>Copyright © 2021, Dewan et al. 2021 Dewan et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c314t-a72f8cafa12e94e7e372c16c15f755bfa7178b49d5d00b26282ba565515a44203</citedby><cites>FETCH-LOGICAL-c314t-a72f8cafa12e94e7e372c16c15f755bfa7178b49d5d00b26282ba565515a44203</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318315/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318315/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,36992,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34336488$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dewan, Pooja</creatorcontrib><creatorcontrib>Chaudhary, Preety</creatorcontrib><creatorcontrib>Gomber, Sunil</creatorcontrib><creatorcontrib>Ahmed, Rafat S</creatorcontrib><creatorcontrib>Kotru, Mrinalini</creatorcontrib><title>Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia</title><title>Curēus (Palo Alto, CA)</title><addtitle>Cureus</addtitle><description>Introduction Central nervous system (CNS) treatment using intrathecal chemotherapy and cranial radiation to enable long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) comes at the cost of neurotoxic side effects and long-term sequelae. We investigated oxidative stress as a possible mechanism of chemotherapy-induced neurotoxicity in children with ALL. Materials and methods In this case-control study, we estimated the cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OH-dG), a DNA damage product, in children with B-cell ALL and control children. CSF samples were collected at diagnosis, at end of Induction 1, Induction 2, and Induction 2A - consolidation phase. CSF 8-OH-dG levels were compared in children with and without neurotoxicity. Results Children with ALL (n=23) at diagnosis had significantly higher median (interquartile range, IQR) CSF 8-OH-dG levels (ng/mL) compared to controls (n=19) [1.97 (1.59-2.56) Vs 0.65 (0.59-0.82), P&lt;0.001]. CSF 8-OH-dG levels at the end of four weeks, eight weeks, and 16 weeks of chemotherapy were [3.96 (2.85-5.44) ng/mL], 1.00 (0.89-1.09), and 3.73 (2.80-4.39) ng/mL, respectively. Out of 23 children with ALL, 12 developed neurotoxicity; the CSF levels of 8-OH-dG in them were only marginally higher compared to those who did not develop neurotoxicity. The CSF 8-OH-dG levels did not show a significant correlation with the number of doses of methotrexate or vincristine received. Conclusion Chemotherapy increases the CNS oxidative stress as measured by CSF 8-OH-dG levels, with the levels being proportional to the intensity of chemotherapy. Children with neurotoxicity had only marginally higher CSF 8-OH-dG levels as compared to children without neurotoxicity.</description><subject>Neurology</subject><subject>Oncology</subject><subject>Pediatrics</subject><issn>2168-8184</issn><issn>2168-8184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNpVkc1LAzEQxYMoVqo3z5KjB1uTbLLJXgSpn1DoQT2HbHbWRvfLZFP0v3dttVQYmIH58eYxD6FTSqZSiuzSRg8xTKnIMrmHjhhN1URRxfd35hE6CeGNEEKJZESSQzRKeJKkXKkjlC8-XWF6twL81HsIAbsGz8BD7tvQucZU-K6KrsA30bvmFT97MH0NTb_mlq4qlm1b4Gsbe8Dzr7pbtnllQu8snkN8h9qZY3RQmirAyW8fo5e72-fZw2S-uH-cXc8nNqG8nxjJSmVNaSiDjIOERDJLU0tFKYXISyOpVDnPClEQkrOUKZYbkQpBheGckWSMrja6XcxrKOxg0ptKd97Vxn_p1jj9f9O4pX5tV1oldCgxCJz_Cvj2I0Lode2ChaoyDbQxaCaEFJywgR6jiw1qhzcFD-X2DCX6Jxm9SUavkxnws11rW_gvh-Qb772MpA</recordid><startdate>20210628</startdate><enddate>20210628</enddate><creator>Dewan, Pooja</creator><creator>Chaudhary, Preety</creator><creator>Gomber, Sunil</creator><creator>Ahmed, Rafat S</creator><creator>Kotru, Mrinalini</creator><general>Cureus</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210628</creationdate><title>Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia</title><author>Dewan, Pooja ; Chaudhary, Preety ; Gomber, Sunil ; Ahmed, Rafat S ; Kotru, Mrinalini</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c314t-a72f8cafa12e94e7e372c16c15f755bfa7178b49d5d00b26282ba565515a44203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Neurology</topic><topic>Oncology</topic><topic>Pediatrics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dewan, Pooja</creatorcontrib><creatorcontrib>Chaudhary, Preety</creatorcontrib><creatorcontrib>Gomber, Sunil</creatorcontrib><creatorcontrib>Ahmed, Rafat S</creatorcontrib><creatorcontrib>Kotru, Mrinalini</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Curēus (Palo Alto, CA)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dewan, Pooja</au><au>Chaudhary, Preety</au><au>Gomber, Sunil</au><au>Ahmed, Rafat S</au><au>Kotru, Mrinalini</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia</atitle><jtitle>Curēus (Palo Alto, CA)</jtitle><addtitle>Cureus</addtitle><date>2021-06-28</date><risdate>2021</risdate><volume>13</volume><issue>6</issue><spage>e15997</spage><pages>e15997-</pages><issn>2168-8184</issn><eissn>2168-8184</eissn><abstract>Introduction Central nervous system (CNS) treatment using intrathecal chemotherapy and cranial radiation to enable long-term disease-free survival from childhood acute lymphoblastic leukemia (ALL) comes at the cost of neurotoxic side effects and long-term sequelae. We investigated oxidative stress as a possible mechanism of chemotherapy-induced neurotoxicity in children with ALL. Materials and methods In this case-control study, we estimated the cerebrospinal fluid (CSF) levels of 8-hydroxy-deoxyguanosine (8-OH-dG), a DNA damage product, in children with B-cell ALL and control children. CSF samples were collected at diagnosis, at end of Induction 1, Induction 2, and Induction 2A - consolidation phase. CSF 8-OH-dG levels were compared in children with and without neurotoxicity. Results Children with ALL (n=23) at diagnosis had significantly higher median (interquartile range, IQR) CSF 8-OH-dG levels (ng/mL) compared to controls (n=19) [1.97 (1.59-2.56) Vs 0.65 (0.59-0.82), P&lt;0.001]. CSF 8-OH-dG levels at the end of four weeks, eight weeks, and 16 weeks of chemotherapy were [3.96 (2.85-5.44) ng/mL], 1.00 (0.89-1.09), and 3.73 (2.80-4.39) ng/mL, respectively. Out of 23 children with ALL, 12 developed neurotoxicity; the CSF levels of 8-OH-dG in them were only marginally higher compared to those who did not develop neurotoxicity. The CSF 8-OH-dG levels did not show a significant correlation with the number of doses of methotrexate or vincristine received. Conclusion Chemotherapy increases the CNS oxidative stress as measured by CSF 8-OH-dG levels, with the levels being proportional to the intensity of chemotherapy. Children with neurotoxicity had only marginally higher CSF 8-OH-dG levels as compared to children without neurotoxicity.</abstract><cop>United States</cop><pub>Cureus</pub><pmid>34336488</pmid><doi>10.7759/cureus.15997</doi><oa>free_for_read</oa></addata></record>
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title Oxidative Stress in Cerebrospinal Fluid During Treatment in Childhood Acute Lymphoblastic Leukemia
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