Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular and Clinical Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9450 Online ISSN: 2049-9469
Journal Cover
December-2020 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2020 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.xls
Article Open Access

Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma

  • Authors:
    • K. Grace Ho
    • Erik N. Uhlmann
    • Eric T. Wong
    • Erik J. Uhlmann
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA 02215, USA, Khoury College of Computer Sciences, Northeastern University, Boston, MA 02115, USA
    Copyright: © Ho et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 80
    |
    Published online on: October 1, 2020
       https://doi.org/10.3892/mco.2020.2150
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The median survival time of patients with glioblastoma is 14‑16 months with a 5‑year overall survival rate of 9.8%. Standard of care treatment includes radiation with concomitant temozolomide followed by cyclic temozolomide. If the patient develops myelosuppression (thrombocytopenia, leukopenia or anemia), the dose of temozolomide is reduced or stopped to avoid bleeding or infections. Recent studies have demonstrated that mild leukopenia is associated with increased overall survival in patients with glioblastoma. To confirm prior results showing that leukopenia is associated with increased overall survival as a primary outcome in patients with glioblastoma, the present study retrospectively collected complete blood counts from 141 patients with glioblastoma treated at the Beth Israel Deaconess Medical Center (Boston, USA) between January 2012 and December 2017. According to Kaplan‑Meier analysis with a log‑rank test, the presence of leukopenia was associated with increased overall survival (P=0.008). Furthermore, patients with grade 2 leukopenia (Common Terminology Criteria for Adverse Events version 5.0) survived longer than those without myelosuppression (P=0.024). There was no difference in overall survival between patients with grade 1, 3 or 4 leukopenia and those without myelosuppression. Leukopenia was associated with longer survival independent of age or extent of surgery in Cox proportional hazards regression modeling (P=0.00205). A possible interpretation is that grade 2 leukopenia is a biomarker of adequate temozolomide dosing in a population with diverse DNA repair function, which may be the consequence of variable O6‑methylguanine‑DNA methyltransferase activity. A prospective dose escalation trial is necessary to determine if treatment‑induced leukopenia is beneficial for all patients receiving temozolomide.
View Figures

Figure 1

View References

1 

Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Jaeckle KA, Armstrong TS, Wefel JS, Won M, Blumenthal DT, et al: Dose-dense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol. 31:4085–4091. 2013.PubMed/NCBI View Article : Google Scholar

2 

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al: Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 10:459–466. 2009.PubMed/NCBI View Article : Google Scholar

3 

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005.PubMed/NCBI View Article : Google Scholar

4 

Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A, Goetz AD, Schwartz G, Edwards T, Reyderman L, et al: Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer. 88:1004–1011. 2003.PubMed/NCBI View Article : Google Scholar

5 

Knizhnik AV, Roos WP, Nikolova T, Quiors S, Tomaszowski K, Christmann M and Kaina B: Survival and death strategies in glioma cells: Autophagy, senescence and apoptosis triggered by a single type of temozolomide-induced DNA damage. PLoS One. 8(e55665)2013.PubMed/NCBI View Article : Google Scholar

6 

Gerson SL, Phillips W, Kastan M, Dumenco LL and Donovan C: Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU. Blood. 88:1649–1655. 1996.PubMed/NCBI

7 

Newlands ES, Stevens MF, Wedge SR, Wheelhouse RT and Brock C: Temozolomide: A review of its discovery, chemical properties, pre-clinical development and clinical trials. Cancer Treat Rev. 23:35–61. 1997.PubMed/NCBI View Article : Google Scholar

8 

Abola MV, Prasad V and Jena AB: Association between treatment toxicity and outcomes in oncology clinical trials. Ann Oncol. 25:2284–2289. 2014.PubMed/NCBI View Article : Google Scholar

9 

Di Maio M, Gridelli C, Gallo C, Shepherd F, Piantedosi FV, Cigolari S, Manzione L, Illiano A, Barbera S, Robbiati SF, et al: Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: A pooled analysis of three randomised trials. Lancel Oncol. 6:669–677. 2005.PubMed/NCBI View Article : Google Scholar

10 

Fontein DB, Seynaeve C, Hadji P, Hille ET, van de Water W, Putter H, Kranenbarg EM, Hasenburg A, Paridaens RJ, Vannetzel JM, et al: Specific adverse events predict survival benefit in patients treated with tamoxifen or aromatase inhibitors: An international tamoxifen exemestane adjuvant multinational trial analysis. J Clin Oncol. 31:2257–2264. 2013.PubMed/NCBI View Article : Google Scholar

11 

Saito T, Sugiyama K, Hama S, Yamasaki F, Takayasu T, Nosaka R, Muragaki Y, Kawamata T and Kurisu K: Prognostic importance of temozolomide-induced neutropenia in glioblastoma, IDH-wildtype patients. Neurosurg Rev. 41:621–628. 2018.PubMed/NCBI View Article : Google Scholar

12 

Vaios EJ, Nahed BV, Muzikansky A, Fathi AT and Dietrich J: Bone marrow response as a potential biomarker of outcomes in glioblastoma patient. J Neurosurg. 127:132–138. 2017.PubMed/NCBI View Article : Google Scholar

13 

Williams M, Liu ZW, Woolf D, Hargreaves S, Michalarea V, Menashy R, Kooner I and Wilson E: Change in platelet levels during radiotherapy with concurrent and adjuvant temozolomide for the treatment of glioblastoma: A novel prognostic factor for survival. J Cancer Res Clin Oncol. 138:1683–1688. 2012.PubMed/NCBI View Article : Google Scholar

14 

Pitter K, Tamagno I, Alikhanyan K, Hosni-Ahmen A, Pattwell SS, Donnola S, Dai C, Ozawa T, Chang M, Chan TA, et al: Corticosteroids compromise survival in glioblastoma. Brain. 139:1458–1471. 2016.PubMed/NCBI View Article : Google Scholar

15 

Boonyawan K, Hess KR, Yang J, Long L, Wang Q, Ezhilarasan R, Auia A, Alfaro-Munoz KD, de Groot JF, Bhat KP and Sulman EP: A relative increase in circulating platelets following chemoradiation predicts for poor survival of patients with glioblastoma. Oncotarget. 8:90488–90495. 2017.PubMed/NCBI View Article : Google Scholar

16 

Armstrong TS, Cao Y, Scheurer ME, Vera-Bolaños E, Manning R, Okcu MF, Bondy M, Zhou R and Gilbert MR: Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors. Neuro Oncol. 11:825–832. 2009.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ho KG, Uhlmann EN, Wong ET and Uhlmann EJ: Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma. Mol Clin Oncol 13: 80, 2020.
APA
Ho, K.G., Uhlmann, E.N., Wong, E.T., & Uhlmann, E.J. (2020). Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma. Molecular and Clinical Oncology, 13, 80. https://doi.org/10.3892/mco.2020.2150
MLA
Ho, K. G., Uhlmann, E. N., Wong, E. T., Uhlmann, E. J."Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma". Molecular and Clinical Oncology 13.6 (2020): 80.
Chicago
Ho, K. G., Uhlmann, E. N., Wong, E. T., Uhlmann, E. J."Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma". Molecular and Clinical Oncology 13, no. 6 (2020): 80. https://doi.org/10.3892/mco.2020.2150
Copy and paste a formatted citation
x
Spandidos Publications style
Ho KG, Uhlmann EN, Wong ET and Uhlmann EJ: Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma. Mol Clin Oncol 13: 80, 2020.
APA
Ho, K.G., Uhlmann, E.N., Wong, E.T., & Uhlmann, E.J. (2020). Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma. Molecular and Clinical Oncology, 13, 80. https://doi.org/10.3892/mco.2020.2150
MLA
Ho, K. G., Uhlmann, E. N., Wong, E. T., Uhlmann, E. J."Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma". Molecular and Clinical Oncology 13.6 (2020): 80.
Chicago
Ho, K. G., Uhlmann, E. N., Wong, E. T., Uhlmann, E. J."Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma". Molecular and Clinical Oncology 13, no. 6 (2020): 80. https://doi.org/10.3892/mco.2020.2150
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team