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Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate
Background High‐dose methotrexate (HD‐MTX; 5000 mg/m2) is an important component of curative therapy in many treatment regimens for high‐risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose‐limiting neurotoxicity, which may disproportionately affect Lat...
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| Published in: | Cancer 2023-04, Vol.129 (8), p.1287-1294 |
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| container_title | Cancer |
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| creator | Harris, Rachel D. Bernhardt, Melanie Brooke Zobeck, Mark C. Taylor, Olga A. Gramatges, Maria Monica Schafer, Eric S. Lupo, Philip J. Rabin, Karen R. Scheurer, Michael E. Brown, Austin L. |
| description | Background
High‐dose methotrexate (HD‐MTX; 5000 mg/m2) is an important component of curative therapy in many treatment regimens for high‐risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose‐limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD‐MTX in an ethnically diverse population of patients with ALL.
Methods
The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD‐MTX at Texas Children's Cancer Center (2010–2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke‐like symptoms) occurring within 21 days of HD‐MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.
Results
Overall, 351 patients (58.1% Latino) who received 1183 HD‐MTX infusions were evaluated. Thirty‐five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three‐fold increased odds (OR, 3.32; 95% CI, 0.98–11.21; p = .05) for neurotoxicity compared with creatinine elevation |
| doi_str_mv | 10.1002/cncr.34646 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2789603676</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2789603676</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3576-ff5aadf7228840d582b4292647ef9fc0cc7479650df17f5d50dd96d1a84ca3363</originalsourceid><addsrcrecordid>eNp9kMtO3DAUhq0KVAbaTR8AWWKHFHBsx06W1YhLJVQkRKXuIo99TAxJnNqOYHbddcsz8iT1dChLVuei73xH-hH6UpKTkhB6qkcdThgXXHxAi5I0siAlpztoQQipi4qzn3toP8b7PEpasY9ojwnR0EbSBfpzlrrR6Zffz3EC7azTeApgnE4-ROwtHmEOPvknp11aYzX48Q5PKjkYU8SPLnV4yrhKIV8qPSfA_XqYOr_qVUx518P8AINTWNkEAXfursvPjI-AB0idTwGeVIJPaNeqPsLn13qAfpyf3S4vi6vri2_Lr1eFZpUUhbWVUsZKSuuaE1PVdMVpQwWXYBuridaSy0ZUxNhS2srkxjTClKrmWjEm2AE62nqn4H_NEFN77-cw5pctlXUjCBNyQx1vKR18jAFsOwU3qLBuS9JuMm83mbf_Ms_w4atyXg1g3tD_IWeg3AKProf1O6p2-X15s5X-BZfxkgY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2789603676</pqid></control><display><type>article</type><title>Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate</title><source>Wiley-Blackwell Read & Publish Collection</source><source>EZB Electronic Journals Library</source><creator>Harris, Rachel D. ; Bernhardt, Melanie Brooke ; Zobeck, Mark C. ; Taylor, Olga A. ; Gramatges, Maria Monica ; Schafer, Eric S. ; Lupo, Philip J. ; Rabin, Karen R. ; Scheurer, Michael E. ; Brown, Austin L.</creator><creatorcontrib>Harris, Rachel D. ; Bernhardt, Melanie Brooke ; Zobeck, Mark C. ; Taylor, Olga A. ; Gramatges, Maria Monica ; Schafer, Eric S. ; Lupo, Philip J. ; Rabin, Karen R. ; Scheurer, Michael E. ; Brown, Austin L.</creatorcontrib><description>Background
High‐dose methotrexate (HD‐MTX; 5000 mg/m2) is an important component of curative therapy in many treatment regimens for high‐risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose‐limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD‐MTX in an ethnically diverse population of patients with ALL.
Methods
The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD‐MTX at Texas Children's Cancer Center (2010–2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke‐like symptoms) occurring within 21 days of HD‐MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.
Results
Overall, 351 patients (58.1% Latino) who received 1183 HD‐MTX infusions were evaluated. Thirty‐five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three‐fold increased odds (OR, 3.32; 95% CI, 0.98–11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six‐fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39–24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%.
Conclusions
The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.
Serum creatinine elevations ≥50% of baseline are associated with an increased risk for methotrexate‐related neurotoxicity among patients with pediatric acute lymphoblastic leukemia of self‐reported Latino ethnicity.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.34646</identifier><identifier>PMID: 36692972</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Acute lymphoblastic leukemia ; Antimetabolites, Antineoplastic - therapeutic use ; chemotherapy ; Child ; Children ; Confidence intervals ; Creatinine ; Health services ; Humans ; Immunomodulators ; Leukemia ; Lymphatic leukemia ; Medical records ; Methotrexate ; Minority & ethnic groups ; Neurotoxicity ; Neurotoxicity Syndromes - epidemiology ; Neurotoxicity Syndromes - etiology ; Oncology ; Patients ; Pediatrics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology ; Retrospective Studies ; Risk factors ; Seizures ; Statistical analysis ; toxicity</subject><ispartof>Cancer, 2023-04, Vol.129 (8), p.1287-1294</ispartof><rights>2023 American Cancer Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3576-ff5aadf7228840d582b4292647ef9fc0cc7479650df17f5d50dd96d1a84ca3363</citedby><cites>FETCH-LOGICAL-c3576-ff5aadf7228840d582b4292647ef9fc0cc7479650df17f5d50dd96d1a84ca3363</cites><orcidid>0000-0001-5802-5073 ; 0000-0002-4081-8195 ; 0000-0002-8191-5477 ; 0000-0003-0978-5863</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36692972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harris, Rachel D.</creatorcontrib><creatorcontrib>Bernhardt, Melanie Brooke</creatorcontrib><creatorcontrib>Zobeck, Mark C.</creatorcontrib><creatorcontrib>Taylor, Olga A.</creatorcontrib><creatorcontrib>Gramatges, Maria Monica</creatorcontrib><creatorcontrib>Schafer, Eric S.</creatorcontrib><creatorcontrib>Lupo, Philip J.</creatorcontrib><creatorcontrib>Rabin, Karen R.</creatorcontrib><creatorcontrib>Scheurer, Michael E.</creatorcontrib><creatorcontrib>Brown, Austin L.</creatorcontrib><title>Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate</title><title>Cancer</title><addtitle>Cancer</addtitle><description>Background
High‐dose methotrexate (HD‐MTX; 5000 mg/m2) is an important component of curative therapy in many treatment regimens for high‐risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose‐limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD‐MTX in an ethnically diverse population of patients with ALL.
Methods
The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD‐MTX at Texas Children's Cancer Center (2010–2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke‐like symptoms) occurring within 21 days of HD‐MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.
Results
Overall, 351 patients (58.1% Latino) who received 1183 HD‐MTX infusions were evaluated. Thirty‐five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three‐fold increased odds (OR, 3.32; 95% CI, 0.98–11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six‐fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39–24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%.
Conclusions
The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.
Serum creatinine elevations ≥50% of baseline are associated with an increased risk for methotrexate‐related neurotoxicity among patients with pediatric acute lymphoblastic leukemia of self‐reported Latino ethnicity.</description><subject>Acute lymphoblastic leukemia</subject><subject>Antimetabolites, Antineoplastic - therapeutic use</subject><subject>chemotherapy</subject><subject>Child</subject><subject>Children</subject><subject>Confidence intervals</subject><subject>Creatinine</subject><subject>Health services</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Leukemia</subject><subject>Lymphatic leukemia</subject><subject>Medical records</subject><subject>Methotrexate</subject><subject>Minority & ethnic groups</subject><subject>Neurotoxicity</subject><subject>Neurotoxicity Syndromes - epidemiology</subject><subject>Neurotoxicity Syndromes - etiology</subject><subject>Oncology</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology</subject><subject>Retrospective Studies</subject><subject>Risk factors</subject><subject>Seizures</subject><subject>Statistical analysis</subject><subject>toxicity</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kMtO3DAUhq0KVAbaTR8AWWKHFHBsx06W1YhLJVQkRKXuIo99TAxJnNqOYHbddcsz8iT1dChLVuei73xH-hH6UpKTkhB6qkcdThgXXHxAi5I0siAlpztoQQipi4qzn3toP8b7PEpasY9ojwnR0EbSBfpzlrrR6Zffz3EC7azTeApgnE4-ROwtHmEOPvknp11aYzX48Q5PKjkYU8SPLnV4yrhKIV8qPSfA_XqYOr_qVUx518P8AINTWNkEAXfursvPjI-AB0idTwGeVIJPaNeqPsLn13qAfpyf3S4vi6vri2_Lr1eFZpUUhbWVUsZKSuuaE1PVdMVpQwWXYBuridaSy0ZUxNhS2srkxjTClKrmWjEm2AE62nqn4H_NEFN77-cw5pctlXUjCBNyQx1vKR18jAFsOwU3qLBuS9JuMm83mbf_Ms_w4atyXg1g3tD_IWeg3AKProf1O6p2-X15s5X-BZfxkgY</recordid><startdate>20230415</startdate><enddate>20230415</enddate><creator>Harris, Rachel D.</creator><creator>Bernhardt, Melanie Brooke</creator><creator>Zobeck, Mark C.</creator><creator>Taylor, Olga A.</creator><creator>Gramatges, Maria Monica</creator><creator>Schafer, Eric S.</creator><creator>Lupo, Philip J.</creator><creator>Rabin, Karen R.</creator><creator>Scheurer, Michael E.</creator><creator>Brown, Austin L.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><orcidid>https://orcid.org/0000-0001-5802-5073</orcidid><orcidid>https://orcid.org/0000-0002-4081-8195</orcidid><orcidid>https://orcid.org/0000-0002-8191-5477</orcidid><orcidid>https://orcid.org/0000-0003-0978-5863</orcidid></search><sort><creationdate>20230415</creationdate><title>Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate</title><author>Harris, Rachel D. ; Bernhardt, Melanie Brooke ; Zobeck, Mark C. ; Taylor, Olga A. ; Gramatges, Maria Monica ; Schafer, Eric S. ; Lupo, Philip J. ; Rabin, Karen R. ; Scheurer, Michael E. ; Brown, Austin L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3576-ff5aadf7228840d582b4292647ef9fc0cc7479650df17f5d50dd96d1a84ca3363</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acute lymphoblastic leukemia</topic><topic>Antimetabolites, Antineoplastic - therapeutic use</topic><topic>chemotherapy</topic><topic>Child</topic><topic>Children</topic><topic>Confidence intervals</topic><topic>Creatinine</topic><topic>Health services</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Leukemia</topic><topic>Lymphatic leukemia</topic><topic>Medical records</topic><topic>Methotrexate</topic><topic>Minority & ethnic groups</topic><topic>Neurotoxicity</topic><topic>Neurotoxicity Syndromes - epidemiology</topic><topic>Neurotoxicity Syndromes - etiology</topic><topic>Oncology</topic><topic>Patients</topic><topic>Pediatrics</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology</topic><topic>Retrospective Studies</topic><topic>Risk factors</topic><topic>Seizures</topic><topic>Statistical analysis</topic><topic>toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harris, Rachel D.</creatorcontrib><creatorcontrib>Bernhardt, Melanie Brooke</creatorcontrib><creatorcontrib>Zobeck, Mark C.</creatorcontrib><creatorcontrib>Taylor, Olga A.</creatorcontrib><creatorcontrib>Gramatges, Maria Monica</creatorcontrib><creatorcontrib>Schafer, Eric S.</creatorcontrib><creatorcontrib>Lupo, Philip J.</creatorcontrib><creatorcontrib>Rabin, Karen R.</creatorcontrib><creatorcontrib>Scheurer, Michael E.</creatorcontrib><creatorcontrib>Brown, Austin L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harris, Rachel D.</au><au>Bernhardt, Melanie Brooke</au><au>Zobeck, Mark C.</au><au>Taylor, Olga A.</au><au>Gramatges, Maria Monica</au><au>Schafer, Eric S.</au><au>Lupo, Philip J.</au><au>Rabin, Karen R.</au><au>Scheurer, Michael E.</au><au>Brown, Austin L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2023-04-15</date><risdate>2023</risdate><volume>129</volume><issue>8</issue><spage>1287</spage><epage>1294</epage><pages>1287-1294</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><abstract>Background
High‐dose methotrexate (HD‐MTX; 5000 mg/m2) is an important component of curative therapy in many treatment regimens for high‐risk pediatric acute lymphoblastic leukemia (ALL). However, methotrexate therapy can result in dose‐limiting neurotoxicity, which may disproportionately affect Latino children. This study evaluated risk factors for neurotoxicity after HD‐MTX in an ethnically diverse population of patients with ALL.
Methods
The authors retrospectively reviewed the medical records of patients who were diagnosed with ALL and treated with HD‐MTX at Texas Children's Cancer Center (2010–2017). Methotrexate neurotoxicity was defined as a neurologic episode (e.g., seizures or stroke‐like symptoms) occurring within 21 days of HD‐MTX that resulted in methotrexate treatment modifications. Mixed effects multivariable logistic regression was used to estimate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between clinical factors and neurotoxicity.
Results
Overall, 351 patients (58.1% Latino) who received 1183 HD‐MTX infusions were evaluated. Thirty‐five patients (10%) experienced neurotoxicity, 71% of whom were Latino. After adjusting for clinical risk factors, the authors observed that serum creatinine elevations ≥50% of baseline were associated with a three‐fold increased odds (OR, 3.32; 95% CI, 0.98–11.21; p = .05) for neurotoxicity compared with creatinine elevation <25%. Notably, predictors of neurotoxicity differed by ethnicity. Specifically, Latino children experienced a nearly six‐fold increase in neurotoxicity odds (OR, 5.80; 95% CI, 1.39–24.17; p = .02) with serum creatinine elevation ≥50% compared with creatinine elevation <25%.
Conclusions
The current findings indicate that serum creatinine elevations ≥50% may be associated with an increased risk for neurotoxicity among Latino children with ALL and may identify potential candidates for therapeutic or supportive care interventions.
Serum creatinine elevations ≥50% of baseline are associated with an increased risk for methotrexate‐related neurotoxicity among patients with pediatric acute lymphoblastic leukemia of self‐reported Latino ethnicity.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36692972</pmid><doi>10.1002/cncr.34646</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5802-5073</orcidid><orcidid>https://orcid.org/0000-0002-4081-8195</orcidid><orcidid>https://orcid.org/0000-0002-8191-5477</orcidid><orcidid>https://orcid.org/0000-0003-0978-5863</orcidid></addata></record> |
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| ispartof | Cancer, 2023-04, Vol.129 (8), p.1287-1294 |
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| subjects | Acute lymphoblastic leukemia Antimetabolites, Antineoplastic - therapeutic use chemotherapy Child Children Confidence intervals Creatinine Health services Humans Immunomodulators Leukemia Lymphatic leukemia Medical records Methotrexate Minority & ethnic groups Neurotoxicity Neurotoxicity Syndromes - epidemiology Neurotoxicity Syndromes - etiology Oncology Patients Pediatrics Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - epidemiology Retrospective Studies Risk factors Seizures Statistical analysis toxicity |
| title | Ethnic‐specific predictors of neurotoxicity among patients with pediatric acute lymphoblastic leukemia after high‐dose methotrexate |
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