Therapeutics of Clinical Drugs CML 4 肆 臨 床 病 程 CML ( ) 1. (chronic phase) 2. (accelerated phase) 3. (blast phase) 85% 10% 2 5~10% 2 20% % (acute

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1 Therapeutics of Clinical Drugs 慢 性 骨 髓 性 白 血 病 中 山 醫 學 大 學 附 設 醫 院 藥 劑 科 藥 師 陳 玉 美 中 山 醫 學 大 學 藥 理 學 科 講 師 李 建 瑩 蔡 敏 鈴 摘 要 90% chronic myeloid leukemia Philadelphia chromosome tyrosine kinase inhibitor 壹 前 言 (chronic myeloid leukemia; CML) (myeloproliferative disorder) 1 30~40% 50~70% 100,000/mm 3 貳 病 因 學 C M L (Philadelphia chromosome) 2,3 90% CML 95% PCR BCR-ABL 9 22 t (9:22) 9 Abelson (ABL) protooncogene 22 breakpoint cluster region (BCR) BCR-ABL ABL (tyrosine kinase; TK) BCR-ABL fusion TK 參 發 生 率 CML % 藥 學 雜 誌 第 107 冊 85

2 Therapeutics of Clinical Drugs CML 4 肆 臨 床 病 程 CML ( ) 1. (chronic phase) 2. (accelerated phase) 3. (blast phase) 85% 10% 2 5~10% 2 20% % (acute myeloid leukemia; AML) 表 一 國 際 衛 生 組 織 (WHO) 對 加 速 期 和 急 性 期 之 定 義 (accelerated phase) (blast phase) 1. (blast) 10~19% (basophils) 20% ,000/mm ,000,000/mm % 30% 伍 治 療 CML CML ( ) (1) (2) (3) PCR TK (allogenic hematopoietic cell transplantation) 5,6 CML 5 (disease free survival rate; DFS rate) 10~20% 5 50~60% CML 7 表 二 CML 對 治 療 之 反 應 定 義 完 全 的 血 液 學 上 的 反 應 (complete hematologic response) /mm /mm 3 <5% basophils 86 THE JOURNAL OF TAIWAN PHARMACY Vol.27 No.2

3 細 胞 基 因 學 上 反 應 (cytogenetic response) (none) Ph+ cells > 95% (minimal) Ph+ cells 66-95% (minor) Ph+ cells 36-65% (partial) Ph+ cells 1-35% (complete) Ph+ cells 0% 分 子 學 上 的 反 應 (molecular response) BCR-ABL (transcription) BCR-ABL 3 (log) Ph+ cells Philadelphia (Ph) chromosomepositive cells hydroxyurea busulfan -interferon Hydroxyurea 50-80% 8 -interferon hydroxyurea -interferon 70-80% 15% interferon hydroxyurea Ara-C CML 60 CML 1996 Druker TK bcr-abl TK STI571 STI571 Bcr-Abl TK ATP Bcr-Abl Bcr-Abl 9 TK imatinib nilotinib dasatinib 陸 藥 物 各 論 一 抗 腫 瘤 藥 物 ( 一 )Hydroxyurea (antimetabolites) S (ribonucleotide reductase) DNA DNA CML mg 2500/mm 3 100,000/mm 3 3 ( 二 )Cytarabine (Cylocide, Ara-C) DNA 20% Ara-C mg/m 2 / 5~ mg/m 2 / 2~5 ( 三 )Busulfan (alkylating agent) DNA 4-8 mg/ ( 12 mg/ ) 1-4 mg/ 2 mg/ 10,000-20,000/mm 3 busulfan 藥 學 雜 誌 第 107 冊 87

4 Therapeutics of Clinical Drugs ( 四 )α-interferon IU IU IU 8 ( 12) IU IU 二 酪 胺 酸 激 酶 抑 制 劑 T K imatinib 10 imatinib dasatinib nilotinib ( 一 )Imatinib (Glivec) 400 mg (blast crisis) 600 mg ( ) 400 mg 600 mg 600 mg 800 mg ( 400 mg 2 ) ( 二 )Dasatinib (Sprycel) 100 mg 140 mg 70 mg mg 2 2 ( 三 )Nilotinib (Tasigna) Nilotinib CYP3A4 ( ketoconazole itraconazole voriconazole clarithromycin telithromycin indinavir ritonavir) nilotinib nilotinib CYP3A4 400 ( 1/2) nilotinib CYP3A4 柒 結 論 CML 88 THE JOURNAL OF TAIWAN PHARMACY Vol.27 No.2

5 TK TK farnesyl transferase decitabine antisense oligonucleotides 參 考 資 料 : 1. Tefferi A. Chronic myeloid disorders: Classification and treatment overview. Semin Hematol, 2001; 38: Maru Y. Molecular biology of chronic myeloid leukemia. Int J Hematol, 2001; 73: Sawyers C. Chronic myeloid leukemia. N Engl J Med, 1999; 340: Lange R, Moloney W, Yamawaki T. Leukemia in atomic bomb survivors. I. General observations. Blood 1954; 9: Mauro M, Druker B. STI571: targeting BCR-ABL as therapy for CML. Oncologist, 2001; 6: Biggs J, Szer J, Crilley P, et al: Treatment of chronic myeloid leukemia with allogeneic bone marrow transplantation after preparation with BuCy2. Blood, 1992; 80: Kantarjian H, Sawyers C, Hochhaus A, et al: Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: Garcia-Manero G, Faderl S, O'Brien S, et al: Chronic myelogenous leukemia: a review and update of therapeutic stragies. Cancer 2003; 98: O'Brien SG, Guilhot F, Larson RA. et a: Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348: Druker BJ, Guilhot F, O'Brien SG, et al: Five year followupof patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: Chronic Myelogenous Leukemia Yu-Mei Chen 1, Chien-Ying Li 2, Min-Ling Tsai 2 Chung Shan Medical University Hospital Department of Pharmacy 1 Chung Shan Medical University Department of Pharmacology 2 Abstract Chronic myelogenous leukemia (CML) is a myeloproliferative disorder. Philadelphia chromosome can be found in 90% patients. CML has a triphasic clinical course: chronic phase, accelerated phase and blast crisis. In chronic phase, it is easy control with medicines. To control symptoms and complications is the major target. CML treatments include cytotoxic agents, Tyrosine kinase inhibitors and allogenic hematopoietic cell transplantation. Although transplantation is the only way to cure CML, most patients choose medical care. This article reviewed cause, pathology, clinical course and medical treatments. 藥 學 雜 誌 第 107 冊 89