Dana Farber Cancer Institute, Department of Pharmacy Services, Boston, MA 02215, USA.
Leuk Res. 2013 Jul;37(7):747-51. doi: 10.1016/j.leukres.2013.04.011. Epub 2013 May 1.
All-trans retinoic acid (ATRA) used for the treatment of APL can lead to the development of differentiation syndrome (DS), a potentially life threatening complication. Since ATRA is metabolized by cytochrome P450 (CYP) enzymes, we sought to identify drug interactions that might be associated with a higher risk for the development of DS in addition to other predictive factors related to the incidence of DS. We identified 60 consecutive patients with APL treated at our institution with ATRA from May 2004 until January 2010. Of the 60 patients identified, 29 (48%) developed DS within a median of 5 days (range 1-31) of ATRA initiation. We did not find any difference in overall incidence of DS whether patients were on concurrent CYP 2C8, 2C9 or 3A4 inhibitors, inducers or substrates. In multivariable analysis, higher peripheral blood blast counts on admission (p=0.04) as well as higher body mass index (p=0.003) were associated with developing DS. Out of the 29 patients with DS, there were 4 early deaths of which 2 were attributed to DS compared to no early deaths in the patients who did not develop DS (p=0.05). Regarding disease-related outcomes, only CR rate was different between patients developing DS versus those who did not develop DS.
全反式维 A 酸（ATRA）用于治疗 APL 可导致分化综合征（DS）的发生，这是一种潜在的危及生命的并发症。由于 ATRA 是由细胞色素 P450（CYP）酶代谢的，我们试图确定除了与 DS 发生率相关的其他预测因素外，可能与 DS 发展风险增加相关的药物相互作用。我们确定了 60 例在我们机构接受 ATRA 治疗的 APL 连续患者，这些患者来自 2004 年 5 月至 2010 年 1 月。在确定的 60 例患者中，有 29 例（48%）在 ATRA 开始后中位数为 5 天（范围 1-31）内发生 DS。我们没有发现同时使用 CYP 2C8、2C9 或 3A4 抑制剂、诱导剂或底物的患者 DS 的总发生率有任何差异。多变量分析显示，入院时外周血原始细胞计数较高（p=0.04）和体重指数较高（p=0.003）与发生 DS 相关。在发生 DS 的 29 例患者中，有 4 例早期死亡，其中 2 例归因于 DS，而未发生 DS 的患者则没有早期死亡（p=0.05）。关于疾病相关结局，仅 DS 患者的完全缓解率与未发生 DS 的患者不同。
