Rapid Progressive Glioblastoma despite Radiation in a Patient with Myelodysplastic Syndrome

The rapidity of glioblastoma progression can be exacerbated by impaired systemic immune surveillance. We describe an elderly woman with advanced 5q– myelodysplastic syndrome (MDS) associated with trilineage dysfunction in hematopoiesis. She also developed multiple solid tumor malignancies including ER/PR-positive and HER2-negative breast cancer, probable lung cancer without histologic confirmation, and primary glioblastoma with a high proliferation index of 80%. Because of low platelet counts of 20,000–30,000/µL that required periodic transfusion and a reduced white cell count of 600–900/µL, she was deemed unsafe to take concomitant daily temozolomide during radiation and her glioblastoma was treated with a shortened course of radiotherapy alone. Her baseline absolute neutrophil count was 110–390/µL, and CD4+ and CD8+ lymphocyte counts were 235/µL and 113/µL, respectively. During the last week of radiation, the patient developed a nonfluent aphasia, increased fatigue, and aspiration pneumonia. A gadolinium-enhanced head MRI, obtained 2 days after completion of radiation and 39 days after biopsy, demonstrated near tripling of the size of the left frontal tumor with a significant amount of adjacent cerebral edema. This case raises the possibility that advanced MDS is a negative immunomodulatory condition that can accelerate glioblastoma progression.

[1]  E. Wong,et al.  Leukopenia is a biomarker for effective temozolomide dosing and predicts overall survival of patients with glioblastoma , 2020, Molecular and clinical oncology.

[2]  E. Wong,et al.  Dexamethasone-Friend or Foe for Patients With Glioblastoma? , 2019, JAMA neurology.

[3]  M. Sperandio,et al.  Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells , 2018, Oncoimmunology.

[4]  B. Nahed,et al.  Sequestration of T-cells in bone marrow in the setting of glioblastoma and other intracranial tumors , 2018, Nature Medicine.

[5]  M. Mehta,et al.  A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913 , 2018, Neuro-oncology.

[6]  P. Fecci,et al.  T-cell Dysfunction in Glioblastoma: Applying a New Framework , 2018, Clinical Cancer Research.

[7]  G. Garcia-Manero,et al.  Myelodysplastic syndromes: 2018 update on diagnosis, risk‐stratification and management , 2018, American journal of hematology.

[8]  F. Lieberman,et al.  Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial , 2017, JAMA.

[9]  A. List,et al.  Lenalidomide: Myelodysplastic syndromes with del(5q) and beyond. , 2017, Seminars in hematology.

[10]  V. Levin,et al.  Impact of bevacizumab administered dose on overall survival of patients with progressive glioblastoma , 2015, Journal of Neuro-Oncology.

[11]  R. Weichselbaum,et al.  STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors. , 2014, Immunity.

[12]  M. Delorenzi,et al.  Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy , 2014, Nature Medicine.

[13]  S. Piantadosi,et al.  Immunosuppression in Patients with High-Grade Gliomas Treated with Radiation and Temozolomide , 2011, Clinical Cancer Research.

[14]  R. Weichselbaum,et al.  The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. , 2011, Cancer research.

[15]  R. Mirimanoff,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. , 2009, The Lancet. Oncology.

[16]  Lei Wu,et al.  The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. , 2009, Microvascular research.

[17]  E. Operskalski,et al.  Screening of blood donors for idiopathic CD4+ T‐lymphocytopenia , 1994, Transfusion.