HGG-54. HISTOLOGICAL AND MOLECULAR CHARACTERIZATION OF HIGH-GRADE BRAIN TUMORS SECONDARY TO TOTAL BODY IRRADIATION FOR HEMATOLOGICAL MALIGNANCIES

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is increasingly used in the treatment of acute leukemias (AL), non-Hodgkin lymphomas and other primary malignancies. However, a growing number of neoplasms secondary to HSCT are reported. The combination of total body irradiation (TBI) and high dose chemotherapy (HD-CT) as conditioning regimen is considered a risk factor. We present four children who survived AL, treated with HSCT and conditioning regimens including TBI/HD-CT. These patients developed a high-grade-brain tumor. We analyzed histological and molecular characteristics of neoplasms. METHODS: Histologically, tumors were assessed for: presence of mitosis, necrosis and vascular proliferation; expression of ki67; expression of neuronal and glial markers, p53 and therapeutic targets. We analyzed the DNA methylation profile (DMP) of all tumors using IlluminaEPICarrays and compared it to the brain tumor classifier which allowed to generate the CNVs. RESULTS: Morphologically two cases were defined as anaplastic astrocytoma, two cases as glioblastoma. Based on the DMP, all cases were found to belong to the methylation class “glioblastoma, IDH wildtype, subclass midline”, hypermutants, with gain of chromosome 1q and loss of 1p. Two cases showed PDGFRA amplification. All patients were treated with Temozolomide combination therapy +/- Bevacizumab and radiation therapy. At progression three patients were treated with checkpoint inhibitors. CONCLUSIONS: The improvement of the precision medicine is fundamental in the therapeutic decision of brain tumors and even more in neoplasms secondary to antiblastic treatments. DMP and CNV have proven to be useful tools to complement the histological characterization of the reported cases.