Hidemitsu Kurosawa1, Akihiko Tanizawa2, Hideki Muramatsu3, Chikako Tono4, Akihiro Watanabe5, Haruko Shima6,7, Masaki Ito8, Yuki Yuza9, Kazuko Hamamoto10, Noriko Hotta11, Masahiko Okada12, Akiko Moriya Saito7, Atsushi Manabe13, Shuki Mizutani14, Souichi Adachi15, Keizo Horibe7, Eiichi Ishii16, Hiroyuki Shimada6,7. 1. Department of Pediatrics, Dokkyo Medical University School of Medicine, Tochigi, Japan. 2. Department of Human Resource Development for Cancer, Faculty of Medical Sciences, University of Fukui, Fukui, Japan. 3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. 4. Department of Pediatrics, Iwate Prefectural Chubu Hospital, Iwate, Japan. 5. Department of Pediatrics, Niigata Cancer Center Hospital, Niigata, Japan. 6. Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan. 7. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 8. Department of Pediatrics, Soma General Hospital, Fukushima, Japan. 9. Department of Hematology and Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 10. Department of Pediatrics, Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital, Hiroshima, Japan. 11. Department of Pediatrics, Japan Community Healthcare Organization Tokuyama Central Hospital, Tokuyama, Japan. 12. Department of Pediatrics, Nagasaki University School of Medicine, Nagasaki, Japan. 13. Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan. 14. Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan. 15. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 16. Department of Pediatrics, Ehime University Graduate School of Medicine, Ehime, Japan.
Abstract
BACKGROUND: The details of the sequential use of imatinib for first-line treatment followed by second-generation tyrosine kinase inhibitors (2G-TKIs) for pediatric chronic myeloid leukemia (CML) are still unknown. This study analyzed clinical responses and adverse effects of the use of 2G-TKIs following imatinib in pediatric chronic phase (CP)-CML. PROCEDURES: The Japanese Pediatric Leukemia/Lymphoma Study Group conducted a retrospective study of patients with newly diagnosed CML from 1996 to 2011. A total of 152 cases that received imatinib as first-line therapy were analyzed. RESULTS: Excluding 46 cases treated with hematopoietic stem cell transplantation before nilotinib and dasatinib became available, 31 of 106 patients changed to 2G-TKIs. The primary reason for changing from imatinib was poor response, followed by intolerance, with the main reason for the latter being musculoskeletal events. Switches from imatinib to 2G-TKIs with intolerance occurred significantly earlier than switches with poor response. Sixteen and 15 patients were treated with nilotinib and dasatinib, respectively, following imatinib therapy. After switching to 2G-TKIs, the response status improved in 63% of evaluable patients. The adverse effect profiles of nilotinib and dasatinib tended to be different, with hyperbilirubinemia observed in 33% of nilotinib-treated patients, but in none of the cases with dasatinib. CONCLUSION: This retrospective study represents the first series of children and adolescents in whom sequential use of imatinib followed by 2G-TKIs was reported. These data provide useful insights into the selection of 2G-TKIs as first-line treatment for children and adolescents with CP-CML.
BACKGROUND: The details of the sequential use of imatinib for first-line treatment followed by second-generation tyrosine kinase inhibitors (2G-TKIs) for pediatric chronic myeloid leukemia (CML) are still unknown. This study analyzed clinical responses and adverse effects of the use of 2G-TKIs following imatinib in pediatric chronic phase (CP)-CML. PROCEDURES: The Japanese Pediatric Leukemia/Lymphoma Study Group conducted a retrospective study of patients with newly diagnosed CML from 1996 to 2011. A total of 152 cases that received imatinib as first-line therapy were analyzed. RESULTS: Excluding 46 cases treated with hematopoietic stem cell transplantation before nilotinib and dasatinib became available, 31 of 106 patients changed to 2G-TKIs. The primary reason for changing from imatinib was poor response, followed by intolerance, with the main reason for the latter being musculoskeletal events. Switches from imatinib to 2G-TKIs with intolerance occurred significantly earlier than switches with poor response. Sixteen and 15 patients were treated with nilotinib and dasatinib, respectively, following imatinib therapy. After switching to 2G-TKIs, the response status improved in 63% of evaluable patients. The adverse effect profiles of nilotinib and dasatinib tended to be different, with hyperbilirubinemia observed in 33% of nilotinib-treated patients, but in none of the cases with dasatinib. CONCLUSION: This retrospective study represents the first series of children and adolescents in whom sequential use of imatinib followed by 2G-TKIs was reported. These data provide useful insights into the selection of 2G-TKIs as first-line treatment for children and adolescents with CP-CML.