Display options
Cite
Garcia CR, Myint ZW, Jayswal R, et al. Hematological adverse events in the management of glioblastoma. J Neurooncol. 2021;doi: 10.1007/s11060-021-03891-8.
Garcia, C. R., Myint, Z. W., Jayswal, R., Wang, C., Morgan, R. M., Butts, A. R., Weiss, H. L., & Villano, J. L. (2021). Hematological adverse events in the management of glioblastoma. Journal of neuro-oncology, . https://doi.org/10.1007/s11060-021-03891-8
Garcia, Catherine R, et al. "Hematological adverse events in the management of glioblastoma." Journal of neuro-oncology vol. (2021). doi: https://doi.org/10.1007/s11060-021-03891-8
Garcia CR, Myint ZW, Jayswal R, Wang C, Morgan RM, Butts AR, Weiss HL, Villano JL. Hematological adverse events in the management of glioblastoma. J Neurooncol. 2021 Nov 24; doi: 10.1007/s11060-021-03891-8. Epub 2021 Nov 24. PMID: 34820776.
Copy Download .nbib Format: NLM
Share it on

J Neurooncol. 2021 Nov 24; doi: 10.1007/s11060-021-03891-8. Epub 2021 Nov 24.

Hematological adverse events in the management of glioblastoma.

Journal of neuro-oncology

Catherine R Garcia, Zin W Myint, Rani Jayswal, Chi Wang, Rachael M Morgan, Allison R Butts, Heidi L Weiss, John L Villano

Affiliations

  1. Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
  2. Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA.
  3. Division of Medical Oncology, University of Kentucky, Lexington, KY, USA.
  4. Division of Cancer Biostatistics, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.
  5. Department of Pharmacy Services, University of Kentucky, Lexington, KY, USA.
  6. Markey Cancer Center, University of Kentucky, Lexington, KY, 40536-0293, USA. [email protected].
  7. Division of Medical Oncology, University of Kentucky, Lexington, KY, USA. [email protected].
  8. Department of Neurology, University of Kentucky, Lexington, KY, USA. [email protected].
  9. Department of Neurosurgery, University of Kentucky, Lexington, KY, USA. [email protected].

PMID: 34820776 DOI: 10.1007/s11060-021-03891-8

Abstract

BACKGROUND: Hematological adverse events (HAEs) are common during treatment for glioblastoma (GBM), usually associated with temozolomide (TMZ). Their clinical value is uncertain, as few investigations have focused on outcomes for HAEs during GBM treatment.

METHODS: We combined data from two randomized clinical trials, RTOG 0525 and RTOG 0825, to analyze HAEs during treatment for GBM. We investigated differences between chemoradiation and adjuvant therapy, and by regimen received during adjuvant treatment.

RESULTS: 1454 patients participated in these trials, of which 1154 (79.4%) developed HAEs. During chemoradiation, 44.4% of patients developed HAEs (54% involving more than one cell line), and were most commonly lymphopenia (50.6%), and thrombocytopenia (47.5%). During adjuvant treatment, 45% of patients presented HAEs (78.6% involving more than one cell line), and were more commonly leukopenia (62.7%), and thrombocytopenia (62.3%). Median overall survival (OS) and progression free survival (PFS) were longer in patients with HAEs (OS 19.4 months and PFS 9.9 months) compared to those with other or no adverse events (OS 14.1 months and PFS 5.9 months). There was no significant difference in survival between grade 1 and/or 2 versus grade 3 and/or 4 HAEs. History of HAEs during chemoradiation was a protective factor for presentation of HAEs during adjuvant therapy.

CONCLUSION: HAEs are common during GBM treatment, and often involve more than one cell line (more likely during adjuvant therapy). HAEs may be associated with prolonged OS and PFS, particularly during adjuvant therapy. HAEs during chemoradiation was a protective factor for HAEs during adjuvant therapy.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: Bevacizumab; Glioblastoma; Hematologic adverse events; Management; Outcomes; Temozolomide

References

  1. Stupp R, Mason WP, van den Bent MJ et al (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996 - PubMed
  2. Dressler EV, Liu M, Garcia CR et al (2019) Patterns and disparities of care in glioblastoma. Neurooncol Pract 6:37–46 - PubMed
  3. Garcia CR, Slone SA, Dolecek TA et al (2019) Primary central nervous system tumor treatment and survival in the United States, 2004–2015. J Neurooncol 144:179–191 - PubMed
  4. Villano JL, Letarte N, Yu JM et al (2012) Hematologic adverse events associated with temozolomide. Cancer Chemother Pharmacol 69:107–113 - PubMed
  5. Gerber DE, Grossman SA, Zeltzman M et al (2007) The impact of thrombocytopenia from temozolomide and radiation in newly diagnosed adults with high-grade gliomas. Neuro Oncol 9:47–52 - PubMed
  6. Armstrong TS, Cao Y, Scheurer ME et al (2009) Risk analysis of severe myelotoxicity with temozolomide: the effects of clinical and genetic factors. Neuro Oncol 11:825–832 - PubMed
  7. Sabharwal A, Waters R, Danson S et al (2011) Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mononuclear cells. Melanoma Res 21:502–508 - PubMed
  8. Dior M, Coriat R, Mir O et al (2012) A rare hematological adverse event induced by bevacizumab: severe thrombocytopenia. Am J Med 125:828–830 - PubMed
  9. Schutz FA, Jardim DL, Je Y et al (2011) Haematologic toxicities associated with the addition of bevacizumab in cancer patients. Eur J Cancer 47:1161–1174 - PubMed
  10. Gilbert MR, Wang M, Aldape KD et al (2013) Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III clinical trial. J Clin Oncol 31:4085–4091 - PubMed
  11. Gilbert MR, Dignam JJ, Armstrong TS et al (2014) A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med 370:699–708 - PubMed
  12. Stupp R, Dietrich PY, Ostermann Kraljevic S et al (2002) Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. J Clin Oncol 20:1375–1382 - PubMed
  13. Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457–481 - PubMed
  14. Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170 - PubMed
  15. Kim WJ, Dho YS, Ock CY et al (2019) Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma. J Neurooncol 143:321–328 - PubMed
  16. Campian JL, Piotrowski AF, Ye X et al (2017) Serial changes in lymphocyte subsets in patients with newly diagnosed high grade astrocytomas treated with standard radiation and temozolomide. J Neurooncol 135:343–351 - PubMed
  17. Lombardi G, Rumiato E, Bertorelle R et al (2015) Clinical and genetic factors associated with severe hematological toxicity in glioblastoma patients during radiation plus temozolomide treatment: a prospective study. Am J Clin Oncol 38:514–519 - PubMed
  18. Dixit S, Baker L, Walmsley V et al (2012) Temozolomide-related idiosyncratic and other uncommon toxicities: a systematic review. Anticancer Drugs 23:1099–1106 - PubMed
  19. Gerson SL, Phillips W, Kastan M et al (1996) Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU. Blood 88:1649–1655 - PubMed
  20. Batalini F, Kaufmann MR, Aleixo GF et al (2019) Temozolomide-induced aplastic anaemia and incidental low-grade B-cell non-Hodgkin lymphoma in a geriatric patient with glioblastoma multiforme. BMJ Case Rep 12(6):e228803 - PubMed
  21. Vandraas K, Tjonnfjord GE, Johannesen TB et al (2016) Persistent bone marrow depression following short-term treatment with temozolomide. BMJ Case Rep. https://doi.org/10.1136/bcr-2016-215797 - PubMed
  22. Murphy AG, Grossman SA (2016) Acute hemolysis in a patient with a newly diagnosed glioblastoma. CNS Oncol 5:125–129 - PubMed
  23. Lewis JA, Petty WJ, Harmon M et al (2015) Hemolytic anemia in two patients with glioblastoma multiforme: a possible interaction between vorinostat and dapsone. J Oncol Pharm Pract 21:220–223 - PubMed
  24. FDA. Temozolomide (marketed as Temodar): Aplastic Anemia. In: Consumer Update. Fall, 2007. Accessed Feb 2018 - PubMed
  25. Vaios EJ, Nahed BV, Muzikansky A et al (2017) Bone marrow response as a potential biomarker of outcomes in glioblastoma patients. J Neurosurg 127:132–138 - PubMed
  26. Williams M, Liu ZW, Woolf D et al (2012) 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 - PubMed
  27. Saito T, Sugiyama K, Hama S et al (2018) Prognostic importance of temozolomide-induced neutropenia in glioblastoma, IDH-wildtype patients. Neurosurg Rev 41:621–628 - PubMed
  28. Trinh VA, Patel SP, Hwu WJ (2009) The safety of temozolomide in the treatment of malignancies. Expert Opin Drug Saf 8:493–499 - PubMed
  29. Mendez JS, Govindan A, Leong J et al (2016) Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma. J Neurooncol 127:329–335 - PubMed
  30. Ku GY, Yuan J, Page DB et al (2010) Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer 116:1767–1775 - PubMed
  31. Hiraoka K, Miyamoto M, Cho Y et al (2006) Concurrent infiltration by CD8+ T cells and CD4+ T cells is a favourable prognostic factor in non-small-cell lung carcinoma. Br J Cancer 94:275–280 - PubMed
  32. Lohr J, Ratliff T, Huppertz A et al (2011) Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-beta. Clin Cancer Res 17:4296–4308 - PubMed
  33. Rocconi RP, Matthews KS, Kemper MK et al (2008) Chemotherapy-related myelosuppression as a marker of survival in epithelial ovarian cancer patients. Gynecol Oncol 108:336–341 - PubMed
  34. Ho KG, Uhlmann EN, Wong ET et al (2020) Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma. Mol Clin Oncol 13:80 - PubMed
  35. Chongsathidkiet P, Jackson C, Koyama S et al (2018) Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med 24:1459–1468 - PubMed
  36. Bunn PA Jr, Crowley J, Kelly K et al (1995) Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 13:1632–1641 - PubMed
  37. Staar S, Rudat V, Stuetzer H et al (2001) Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy–results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 50:1161–1171 - PubMed
  38. Lin AJ, Campian JL, Hui C et al (2018) Impact of concurrent versus adjuvant chemotherapy on the severity and duration of lymphopenia in glioma patients treated with radiation therapy. J Neurooncol 136:403–411 - PubMed
  39. Chan A, Fu WH, Shih V et al (2011) Impact of colony-stimulating factors to reduce febrile neutropenic events in breast cancer patients receiving docetaxel plus cyclophosphamide chemotherapy. Support Care Cancer 19:497–504 - PubMed
  40. Chan A, Lee CP, Chiang J et al (2013) Breakthrough febrile neutropenia and associated complications among elderly cancer patients receiving myelosuppressive chemotherapy for solid tumors and lymphomas. Support Care Cancer 21:2137–2143 - PubMed

Publication Types

Grant support