Potential role for second‑generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia harboring additional clonal chromosome abnormalities: A retrospective CML Cooperative Study Group analysis

Ishikawa,Maho; Iriyama,Noriyoshi; Tokuhira,Michihide; Takaku,Tomoiku; Sato,Eriko; Sugimoto,Kei‑Ji; Nakazato,Tomonori; Fujita,Hiroyuki; Kimura,Yuta; Fujioka,Isao; Komatsu,Norio; Asou,Norio; Kizaki,Masahiro; Hatta,Yoshihiro; Kawaguchi,Tatsuya

doi:10.3892/or.2019.7339

Potential role for second‑generation tyrosine kinase inhibitors in patients with chronic myeloid leukemia harboring additional clonal chromosome abnormalities: A retrospective CML Cooperative Study Group analysis

Authors:
- Maho Ishikawa
- Noriyoshi Iriyama
- Michihide Tokuhira
- Tomoiku Takaku
- Eriko Sato
- Kei‑Ji Sugimoto
- Tomonori Nakazato
- Hiroyuki Fujita
- Yuta Kimura
- Isao Fujioka
- Norio Komatsu
- Norio Asou
- Masahiro Kizaki
- Yoshihiro Hatta
- Tatsuya Kawaguchi
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Affiliations: Department of Hemato‑Oncology, Saitama Medical University International Medical Center, Saitama 350‑1298, Japan, Division of Hematology and Rheumatology, Department of Medicine, Nihon University School of Medicine, Tokyo 173‑8610, Japan, Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama 350‑8550, Japan, Department of Hematology, Juntendo University School of Medicine, Tokyo 113‑8431, Japan, Department of Hematology, Juntendo University Nerima Hospital, Tokyo 177‑8521, Japan, Department of Hematology, Juntendo University Urayasu Hospital, Chiba 279‑0021, Japan, Department of Hematology, Yokohama Municipal Citizen's Hospital, Kanagawa 240‑8555, Japan, Department of Hematology, Saiseikai Yokohama Nanbu Hospital, Kanagawa 234‑0054, Japan, Department of Hematology and Infectious Diseases, Kumamoto University Hospital, Kumamoto 860‑8556, Japan
Published online on: September 27, 2019 https://doi.org/10.3892/or.2019.7339
Pages: 2836-2843

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Abstract

Tyrosine kinase inhibitor (TKI) treatment is the standard of care for patients with chronic myeloid leukemia (CML). Even in the imatinib era, the presence of ‘clonal chromosomal abnormalities’ in the Philadelphia chromosome (CCA/Ph+) at diagnosis reportedly increased the risk of disease progression and predicted shorter survival. However, it remains unclear whether CCA/Ph+ is a poor prognostic marker in the era of new‑generation TKIs. The data of patients with CML in the chronic phase (CP) that were extracted from the CML Cooperative Study Group database were retrospectively analyzed. Of the 328 eligible patients, 33 (10.1%) had CCA/Ph+, including 9 major route and 24 minor route aberrations. The characteristics of patients with and without CCA/Ph+ were similar; however, the proportion of blasts was higher among patients with CCA/Ph+. Notably, the survival rate of patients with CCA/Ph+ was not inferior to that of patients without CCA/Ph+, and there were no differences in responses to TKIs. All 9 patients with major route CCA/Ph+ attained a major molecular response (MMR) with no disease progression, and 8 ultimately achieved a deep molecular response. In particular, the median interval between TKI initiation and achievement of MMR was shorter in patients initially treated with a second‑generation TKI than in those treated with imatinib (5 vs. 10 months). The present retrospective study, thus, revealed favorable treatment outcomes in CML‑CP patients with CCA/Ph+ treated with second‑generation TKIs. The data indicated that administering second‑generation TKIs as first‑line treatments is preferable in CML‑CP patients with CCA/Ph+.

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