Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group

Hidemitsu Kurosawa, Akihiko Tanizawa, Hideki Muramatsu, Chikako Tono, Akihiro Watanabe, Haruko Shima, Masaki Ito, Yuki Yuza, Kazuko Hamamoto, Noriko Hotta, Masahiko Okada, Akiko Moriya Saito, Atsushi Manabe, Shuki Mizutani, Souichi Adachi, Keizo Horibe, Eiichi Ishii, Hiroyuki Shimada

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalPediatric Blood and Cancer
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Lymphoma
Leukemia
Pediatrics
Leukemia, Myeloid, Chronic Phase
Therapeutics
Retrospective Studies
Hyperbilirubinemia
Hematopoietic Stem Cell Transplantation
Imatinib Mesylate
Dasatinib
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide

Keywords

  • CML
  • dasatinib
  • imatinib
  • nilotinib

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

Cite this

Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia : A report from the Japanese Pediatric Leukemia/Lymphoma Study Group. / Kurosawa, Hidemitsu; Tanizawa, Akihiko; Muramatsu, Hideki; Tono, Chikako; Watanabe, Akihiro; Shima, Haruko; Ito, Masaki; Yuza, Yuki; Hamamoto, Kazuko; Hotta, Noriko; Okada, Masahiko; Saito, Akiko Moriya; Manabe, Atsushi; Mizutani, Shuki; Adachi, Souichi; Horibe, Keizo; Ishii, Eiichi; Shimada, Hiroyuki.

In: Pediatric Blood and Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Kurosawa, H, Tanizawa, A, Muramatsu, H, Tono, C, Watanabe, A, Shima, H, Ito, M, Yuza, Y, Hamamoto, K, Hotta, N, Okada, M, Saito, AM, Manabe, A, Mizutani, S, Adachi, S, Horibe, K, Ishii, E & Shimada, H 2018, 'Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group', Pediatric Blood and Cancer. https://doi.org/10.1002/pbc.27368
Kurosawa, Hidemitsu ; Tanizawa, Akihiko ; Muramatsu, Hideki ; Tono, Chikako ; Watanabe, Akihiro ; Shima, Haruko ; Ito, Masaki ; Yuza, Yuki ; Hamamoto, Kazuko ; Hotta, Noriko ; Okada, Masahiko ; Saito, Akiko Moriya ; Manabe, Atsushi ; Mizutani, Shuki ; Adachi, Souichi ; Horibe, Keizo ; Ishii, Eiichi ; Shimada, Hiroyuki. / Sequential use of second-generation tyrosine kinase inhibitors following imatinib therapy in pediatric chronic myeloid leukemia : A report from the Japanese Pediatric Leukemia/Lymphoma Study Group. In: Pediatric Blood and Cancer. 2018.
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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.",
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T2 - A report from the Japanese Pediatric Leukemia/Lymphoma Study Group

AU - Kurosawa, Hidemitsu

AU - Tanizawa, Akihiko

AU - Muramatsu, Hideki

AU - Tono, Chikako

AU - Watanabe, Akihiro

AU - Shima, Haruko

AU - Ito, Masaki

AU - Yuza, Yuki

AU - Hamamoto, Kazuko

AU - Hotta, Noriko

AU - Okada, Masahiko

AU - Saito, Akiko Moriya

AU - Manabe, Atsushi

AU - Mizutani, Shuki

AU - Adachi, Souichi

AU - Horibe, Keizo

AU - Ishii, Eiichi

AU - Shimada, Hiroyuki

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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KW - dasatinib

KW - imatinib

KW - nilotinib

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