Kondo Toshinori, Tasaka Taizo, Matsumoto Kana, Matsumoto Rui, Koresawa Lisa, Sano Fuminori, Tokunaga Hirotoshi, Matsuhashi Yoshiko, Nakanishi Hidekazu, Morita Kunihiko, Wada Hideho, Sugihara Takashi
Division of Hematology, Kawasaki Medical School, 577, Matsushima, Kurashiki, Okayama, 701-0192 Japan.
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe, Kyoto, 610-0395 Japan.
Springerplus. 2014 Apr 5;3:177. doi: 10.1186/2193-1801-3-177. eCollection 2014.
Central nervous system (CNS) relapse is a critical issue while treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). A 58-year-old woman with Ph-positive ALL who relapsed after bone marrow transplantation for meningeal leukemia was treated with high-dose methotrexate, which resulted in remission. She underwent allogeneic cord blood transplantation followed by reduced intensity conditioning chemotherapy with imatinib; however, she experienced CNS relapse and developed an extramedullary mass on the right side of the temporal region. We treated 40 mg of dasatinib once daily, which had to be temporarily discontinued because she developed grade 2 pleural effusion and grade 2 hematemesis. After reinitiation of dasatinib, the extramedullary mass disappeared and meningeal leukemia ameliorated almost immediately. With 40 mg dasatinib administered once daily, its trough level and cerebrospinal fluid (CSF) concentration were 32 ng/mL and below the sensitivity threshold of 1 ng/mL, respectively. Treatment was continued, and the patient remained in complete remission until she died of pneumonia 7 years after the initial diagnosis of ALL. Dasatinib can be an effective treatment for Ph-positive ALL with CNS relapse. Although the concentration in the CSF seems low, it may be sufficient to exert anti-leukemic effects in the human CNS.
中枢神经系统(CNS)复发是治疗费城染色体阳性急性淋巴细胞白血病(Ph阳性ALL)时的一个关键问题。一名58岁的Ph阳性ALL女性,在接受骨髓移植治疗脑膜白血病后复发,接受了大剂量甲氨蝶呤治疗,病情缓解。她接受了异基因脐血移植,随后用伊马替尼进行了减低强度预处理化疗;然而,她出现了CNS复发,并在颞区右侧形成了一个髓外肿块。我们给予她每日一次40毫克达沙替尼治疗,但由于她出现了2级胸腔积液和2级呕血,不得不暂时停药。重新开始使用达沙替尼后,髓外肿块几乎立即消失,脑膜白血病病情改善。每日一次给予40毫克达沙替尼时,其谷浓度和脑脊液(CSF)浓度分别为32纳克/毫升和低于1纳克/毫升的检测阈值。治疗持续进行,该患者一直处于完全缓解状态,直到在ALL初始诊断7年后死于肺炎。达沙替尼可有效治疗伴有CNS复发的Ph阳性ALL。尽管脑脊液中的浓度似乎较低,但可能足以在人体中枢神经系统中发挥抗白血病作用。