Yamane Hiroaki, Ide Kentaro, Tanaka Asuka, Hashimoto Shinji, Nagoshi Hisao, Tahara Hiroyuki, Ohira Masahiro, Seidakhmetov Akhmet, Marlen Doskali, Tanaka Yuka, Ohdan Hideki
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Transplant Proc. 2020 Mar;52(2):600-603. doi: 10.1016/j.transproceed.2019.06.006. Epub 2019 Nov 14.
Chronic myeloid leukemia (CML) is a rare malignancy in kidney transplant (KT) recipients. Although dasatinib is the first-line treatment for CML, it has inhibitory activity against CYP3A4; this might increase the blood concentration of tacrolimus (administered to KT patients for immune suppression). Furthermore, tacrolimus can also increase blood concentrations of dasatinib through P-glycoprotein inhibition.
Here, we report a case of sustained molecular remission of CML with prolonged first-line dasatinib therapy in a KT recipient being treated with tacrolimus. A 61-year-old woman developed CML-chronic phase (CML-CP) 38 months post KT. Her maintenance immunosuppressive therapy consisted of tacrolimus, mycophenolate mofetil, and methylprednisolone. Considering the potential drug interaction with tacrolimus, dasatinib was administered at a low dose of 50 mg/day. Her immune status was evaluated regularly by assessing the mixed lymphocyte reaction (MLR) using an intracellular carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeling technique; immunosuppressive therapy was adjusted accordingly.
The patient achieved complete hematologic remission (CHR) after 1 month of dasatinib treatment. Six months after dasatinib treatment, she achieved a major molecular response. During the observation period, neither antibody-mediated nor acute cellular rejection were encountered in the patient. She remained in CHR with a major molecular response 12 months after the diagnosis of CML-CP.
Data obtained from immune monitoring assays using CFSE-MLR helped us to successfully manage a KT recipient with CML-CP being treated with dasatinib. Drug-drug interactions are a key consideration while designing treatment regimens; such strategies would ensure that drug-drug interactions do not negatively affect the treatment outcomes.
慢性粒细胞白血病(CML)在肾移植(KT)受者中是一种罕见的恶性肿瘤。尽管达沙替尼是CML的一线治疗药物,但它对细胞色素P450 3A4(CYP3A4)具有抑制活性;这可能会增加他克莫司(用于KT患者免疫抑制)的血药浓度。此外,他克莫司也可通过抑制P-糖蛋白增加达沙替尼的血药浓度。
在此,我们报告1例接受他克莫司治疗的KT受者经一线达沙替尼长期治疗后实现CML持续分子缓解的病例。一名61岁女性在KT术后38个月发生慢性期慢性粒细胞白血病(CML-CP)。她的维持性免疫抑制治疗包括他克莫司、霉酚酸酯和甲泼尼龙。考虑到达沙替尼与他克莫司之间潜在的药物相互作用,以50mg/天的低剂量给予达沙替尼。通过使用细胞内羧基荧光素二乙酸琥珀酰亚胺酯(CFSE)标记技术评估混合淋巴细胞反应(MLR)定期评估她的免疫状态;并据此调整免疫抑制治疗。
达沙替尼治疗1个月后患者实现完全血液学缓解(CHR)。达沙替尼治疗6个月后,她达到主要分子反应。在观察期内,患者未发生抗体介导的排斥反应或急性细胞排斥反应。在诊断CML-CP 12个月后,她仍处于CHR且有主要分子反应。
使用CFSE-MLR进行免疫监测分析获得的数据帮助我们成功管理了1例接受达沙替尼治疗的CML-CP的KT受者。在设计治疗方案时,药物相互作用是一个关键考虑因素;此类策略将确保药物相互作用不会对治疗结果产生负面影响。