{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T16:37:50Z","timestamp":1769445470330,"version":"3.49.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Myelotoxicity is a well-known adverse effect of alkylating chemotherapy for glioblastoma. While risk factors during first-line therapy are established, little is known about myelotoxicity recurrence in second-line treatment. This study investigates whether first-line myelotoxicity therapy predisposes patients to recurrence in the second-line setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of 589 patients with glioblastoma treated at the Brain Tumor Centre Amsterdam (2005-2022). Of these, 178 received second-line lomustine or rechallenge temozolomide. Myelotoxicity severity was predominantly assessed using nadir hematological values and its duration. A log-link generalized linear model evaluated associations between first-line and second-line myelotoxicity severity, adjusting for covariates. Cox proportional hazards models assessed time to myelotoxicity onset.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 151 patients (mean age 57.1\u2009\u00b1\u200911.8\u2009years; 66.9% male). Lomustine was given to 66.9%. Myelotoxicity occurred in 73.5% of patients, with 19.9% developing severe toxicity. First-line myelotoxicity severity was significantly associated with second-line severity (\u03b2\u2009=\u20091.3, P &amp;lt; .001). Lomustine correlated with higher myelotoxicity severity than temozolomide (\u03b2\u2009=\u20091.4, P = .002). Higher first-line myelotoxicity scores predicted earlier onset of any-grade (HR\u2009=\u20091.4, P &amp;lt; .001) and severe (HR =2.1, P &amp;lt; .001) myelotoxicity in second-line therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>First-line myelotoxicity for glioblastoma predicts its recurrence and earlier onset in second-line therapy. Patients with toxicity in first-line have an increased risk of severe hematological toxicity upon re-exposure. Lomustine carries a higher risk for myelotoxicity than temozolomide. These findings suggest an inherent predisposition to alkylating chemotherapy-induced myelotoxicity for a subgroup of patients. Integrating prior myelotoxicity history into second-line treatment decisions may improve risk stratification and guide monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf411","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:10:00Z","timestamp":1765545000000},"source":"Crossref","is-referenced-by-count":0,"title":["Recurrent hematological toxicity after second-line treatment in patients with glioblastoma: indication of a potential predisposition"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3040-6692","authenticated-orcid":false,"given":"Leon","family":"van Hout","sequence":"first","affiliation":[{"name":"Department of Neurology, Amsterdam UMC , De Boelelaan 1117 , Amsterdam, 1081HV,","place":["The Netherlands"]},{"name":"Department of Neurosurgery, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]},{"name":"Cancer Center Amsterdam, Treatment and Quality of Life , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Femke E L","family":"van den Elzen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam UMC , De Boelelaan 1117 , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zo\u00eb","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam UMC , De Boelelaan 1117 , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nienke","family":"Grun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam UMC , De Boelelaan 1117 , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martinus P G","family":"Broen","sequence":"additional","affiliation":[{"name":"Department of Neurology, GROW School for Oncology and Reproduction, Maastricht University Medical Centre , Maastricht, 6229ER,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imke","family":"Bartelink","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy & Pharmacology, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M E","family":"Bruynzeel","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank J","family":"Lagerwaard","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-1070","authenticated-orcid":false,"given":"Jan","family":"Buter","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William Peter","family":"Vandertop","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]},{"name":"Cancer Center Amsterdam, Treatment and Quality of Life , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart A","family":"Westerman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Cancer Center Amsterdam, Amsterdam UMC , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit I","family":"Lissenberg\u2014Witte","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam UMC, Vrije Universiteit Amsterdam , Amsterdam, 1081HV,","place":["The Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5252-4365","authenticated-orcid":false,"given":"Mathilde C M","family":"Kouwenhoven","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam UMC , De Boelelaan 1117 , Amsterdam, 1081HV,","place":["The Netherlands"]},{"name":"Cancer Center Amsterdam, Treatment and Quality of Life , Amsterdam, 1081HV,","place":["The Netherlands"]},{"name":"Cancer Center Amsterdam, Imaging and Biomarkers , Amsterdam, 1081HV,","place":["The 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