Michael Karremann1, Nadja Krämer2, Marion Hoffmann3, Maria Wiese3, Andreas Beilken4, Selim Corbacioglu5, Dagmar Dilloo6, Pablo Hernáiz Driever7, Wolfram Scheurlen8, Andreas Kulozik9, Gerrit H Gielen10, André O von Bueren11, Matthias Dürken2, Christof M Kramm3. 1. Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: michael.karremann@umm.de. 2. Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. 3. Division of Pediatric Hematology and Oncology, Department of Child and Adolescent Health, University Medical Center Göttingen, Göttingen, Germany. 4. Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany. 5. Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Children's Hospital Regensburg, Regensburg, Germany. 6. Department of Pediatric Hematology and Oncology, Center for Child and Adolescent Medicine, Rheinische Friedrich-Wilhelms University, Bonn, Germany. 7. Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, Berlin, Germany. 8. Cnopf'sche Kinderklinik, Nürnberg Children's Hospital, Nürnberg, Germany. 9. Department of Pediatric Hematology, Oncology and Immunology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany. 10. Department of Neuropathology, University Hospital Bonn, 53105 Bonn, Germany. 11. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland.
Abstract
BACKGROUND: Temozolomide (TMZ) is widely used in high-grade glioma (HGG). There is a major concern of treatment-induced secondary haematological malignancies (SHMs). Due to the poor overall survival of HGG patients, the true incidence is yet elusive. Thus, the aim of this study was to determine the risk of SHMs following TMZ in paediatric HGG. METHODS: We analysed 487 patients from the HIT-HGG database of the German-speaking Society of Pediatric Oncology and Hematology with follow up beyond 1 year. RESULTS: The incidence of SHM was 7.7 ± 3.2% at 10 years. No SHM occurred in 194 patients after first-line TMZ therapy, but four out of 131 patients treated with TMZ for relapse following first-line multiagent chemotherapy experienced SHM (20% at 10 years; p = 0.041). SHMs occurred in two out of 162 patients who underwent multiagent chemotherapy without TMZ (4.1% at 10 years). Gender, patient age and acute haematological toxicity during treatment did not affect the incidence of SHMs. CONCLUSION: Data of our cohort do not indicate an increased risk of SHM following TMZ treatment when compared to previous chemotherapy regimen. However, if TMZ is administered as a second-line treatment following conventional chemotherapy regimen, the risk might be disproportionately increasing.
BACKGROUND:Temozolomide (TMZ) is widely used in high-grade glioma (HGG). There is a major concern of treatment-induced secondary haematological malignancies (SHMs). Due to the poor overall survival of HGG patients, the true incidence is yet elusive. Thus, the aim of this study was to determine the risk of SHMs following TMZ in paediatric HGG. METHODS: We analysed 487 patients from the HIT-HGG database of the German-speaking Society of Pediatric Oncology and Hematology with follow up beyond 1 year. RESULTS: The incidence of SHM was 7.7 ± 3.2% at 10 years. No SHM occurred in 194 patients after first-line TMZ therapy, but four out of 131 patients treated with TMZ for relapse following first-line multiagent chemotherapy experienced SHM (20% at 10 years; p = 0.041). SHMs occurred in two out of 162 patients who underwent multiagent chemotherapy without TMZ (4.1% at 10 years). Gender, patient age and acute haematological toxicity during treatment did not affect the incidence of SHMs. CONCLUSION: Data of our cohort do not indicate an increased risk of SHM following TMZ treatment when compared to previous chemotherapy regimen. However, if TMZ is administered as a second-line treatment following conventional chemotherapy regimen, the risk might be disproportionately increasing.
Authors: Meng Liu; Jigisha P Thakkar; Catherine R Garcia; Therese A Dolecek; Lars M Wagner; Emily Van Meter Dressler; John L Villano Journal: Cancer Med Date: 2018-03-13 Impact factor: 4.452