Shi Jun, Chang Hong, Zhang Li, Shao Yinqi, Nie Neng, Zhang Jing, Huang Jinbo, Zhang Li, Tang Xudong, Quan Richeng, Zheng Chunmei, Xiao Haiyan, Hu Dengming, Hu Lingyan, Liu Feng, Zhou Yongming, Zheng Yizhou, Zhang Fengkui
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.
Department of Hematology and Research Laboratory of Hematology, West China Hospital of Sichuan University, Chengdu 610041, China.
Zhonghua Xue Ye Xue Za Zhi. 2016 Jan;37(1):1-6. doi: 10.3760/cma.j.issn.0253-2727.2016.01.001.
To explore the efficacy and safety of deferasirox in aplastic anemia (AA)patients with iron overload.
A single arm, multi- center, prospective, open- label study was conducted to evaluate absolute change in serum ferritin (SF)from baseline to 12 months of deferasirox administration, initially at a dose of 20 mg·kg(-1)·d(-1), and the safety in 64 AA patients with iron overload.
All patients started their deferasirox treatment with a daily dose of 20 mg · kg(-1) ·d(-1). The mean actual dose was (18.6±3.60) mg · kg(-1)·d(-1). The median SF decreased from 4 924 (2 718- 6 765)μg/L at baseline (n=64) to 3 036 (1 474- 5 551)μg/L at 12 months (n=23) with the percentage change from baseline as 38%. A median SF decrease of 651 (126-2 125)μg/L was observed at the end of study in 23 patients who completed 12 months' treatment, the median SF level decreased by 1 167(580-4 806)μg/L [5 271(3 420-8 278)μg/L at baseline; 3 036(1 474-5 551)μg/L after 12 months' treatment; the percentage change from baseline as 42% ] after 12 months of deferasirox treatment. The most common adverse events (AEs) were increased serum creatinine levels (40.98%), gastrointestinal discomfort (40.98%), elevated liver transaminase (ALT: 21.31%; AST: 13.11%)and proteinuria (24.59%). The increased serum creatinine levels were reversible and non-progressive. Of 38 patients with concomitant cyclosporine use, 12(31.8%)patients had two consecutive values >ULN, 10(26.3%)patients had two consecutive values >1.33 baseline values, but only 1(2.6%)patient's serum creatinine increased more than 1.33 baseline values and exceeded ULN. For both AST and ALT, no patients experienced two post- baseline values >5 ×ULN or >10 × ULN during the whole study. In AA patients with low baseline PLT count (less than 50 × 10(9)/L), there was no decrease for median PLT level during 12 months' treatment period.
AA patients with iron overload could achieve satisfactory efficacy of iron chelation by deferasirox treatment. The drug was well tolerated with a clinically manageable safety profile and no major adverse events.
探讨地拉罗司在伴有铁过载的再生障碍性贫血（AA）患者中的疗效和安全性。
开展一项单臂、多中心、前瞻性、开放标签研究，以评估64例伴有铁过载的AA患者在给予地拉罗司治疗（初始剂量为20mg·kg⁻¹·d⁻¹）12个月期间血清铁蛋白（SF）相对于基线的绝对变化情况及其安全性。
所有患者均以每日20mg·kg⁻¹·d⁻¹的剂量开始地拉罗司治疗。平均实际剂量为（18.6±3.60）mg·kg⁻¹·d⁻¹。SF中位数从基线时的4924（2718 - 6765）μg/L（n = 64）降至12个月时的3036（1474 - 5551）μg/L（n = 23），相对于基线的变化百分比为38%。在完成12个月治疗的23例患者中，研究结束时观察到SF中位数下降了651（126 - 2125）μg/L，地拉罗司治疗12个月后，SF中位数水平下降了1167（580 - 4806）μg/L[基线时为5271（3420 - 8278）μg/L；治疗12个月后为3036（1474 - 5551）μg/L；相对于基线的变化百分比为42%]。最常见的不良事件（AE）为血清肌酐水平升高（40.98%）、胃肠道不适（40.98%）、肝转氨酶升高（谷丙转氨酶：21.31%；谷草转氨酶：13.11%）和蛋白尿（24.59%）。血清肌酐水平升高是可逆的且无进行性加重。在38例同时使用环孢素的患者中，12例（31.8%）患者连续两次值>正常上限（ULN），10例（26.3%）患者连续两次值>1.33倍基线值，但只有1例（2.6%）患者的血清肌酐升高超过1.33倍基线值且超过ULN。对于谷草转氨酶和谷丙转氨酶，在整个研究期间均无患者出现两次基线后值>5×ULN或>10×ULN。在基线血小板计数低（低于50×10⁹/L）的AA患者中，在12个月治疗期间血小板中位数水平没有下降。
伴有铁过载的AA患者通过地拉罗司治疗可实现满意的铁螯合疗效。该药物耐受性良好，具有临床可控的安全性，且无重大不良事件。
