title: Prolonged and severe thrombocytopenia with pancytopenia induced by radiation-combined temozolomide therapy in a patient with newly diagnosed glioblastoma--analysis of O6-methylguanine-DNA methyltransferase status.
abstract: We report a case of a 51-year-old woman with newly diagnosed glioblastoma multiforme (GBM) who was treated with surgery followed by the standard concomitant temozolomide (TMZ) and radiotherapy (RT). Although TMZ is generally safe and well-tolerated, she developed a sudden onset of prolonged and severe thrombocytopenia as the most prominent event of pancytopenia during the combined treatment, leading to discontinuation of the combined therapy. Thrombocytopenia lasted for more than 2 months with intensive, intermittent platelet transfusions. A bone marrow aspiration and biopsy performed after recovery of severe suppression still revealed reduced number of megakaryocytes. O(6)-methylguanine-DNA methyltransferase (MGMT) analyses showed methylated MGMT promoter in GBM, but unmethylated promoters in both peripheral blood leukocytes and bone marrow cells. This is the first report suggesting the irrelevance of MGMT status of normal hematopoietic cells to TMZ-induced severe thrombocytopenia and pancytopenia.
authors.affiliation: Department of Neurosurgery, Kyorin University Faculty of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan. nagane-nsu@umin.ac.jp
authors.forename: Motoo
authors.initials: M
authors.lastname: Nagane
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nozue
authors.forename: Saki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyazaki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurita
authors.forename: Masashi
authors.initials: M
authors.lastname: Homori
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Shiokawa
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects; D001483:Base Sequence; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000187:drug effects* / Q000235:genetics; D045643:DNA Repair Enzymes / Q000187:drug effects* / Q000235:genetics; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D019635:Neurosurgical Procedures; D010198:Pancytopenia / Q000209:etiology*; D016133:Polymerase Chain Reaction; D011878:Radiotherapy / Q000009:adverse effects; D000077204:Temozolomide; D013921:Thrombocytopenia / Q000209:etiology*; D025521:Tumor Suppressor Proteins / Q000187:drug effects* / Q000235:genetics
chemical_list: D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide