Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome - a phase-II study
Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome - a phase-II study
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DOI：
10.1111/j.1365-2141.2008.07294.x
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发表时间：
2008-12-01
影响因子：
6.5
通讯作者：
Reiter, Andreas
中科院分区：
文献类型：
--
作者：
Metzgeroth, Georgia;Walz, Christoph;Reiter, Andreas
本研究评价了伊马替尼治疗慢性嗜酸性粒细胞白血病（CEL，n = 23）和高嗜酸性粒细胞综合征（HES，n = 13）的疗效和安全性。在用FIP 1 L1-PDGFRA（n = 16）或各种PDGFRB融合基因（n = 5）的CEL中，在3个月后95%（20/21）实现完全血液学缓解（complete haematological remission，CML）。FIP 1 L1-PDGFRA阳性的CEL患者6个月时有75%（12/16）达到完全分子缓解（CMR），12个月后有87%（13/15）达到完全分子缓解。5例PDGFRB融合阳性患者中有3例分别在3、9和18个月后实现CMR。所有患者目前均接受伊马替尼治疗（100 mg; n = 13，400 mg; n = 8），尚未观察到分子复发（中位26.7个月;范围6.9-39.9）。伊马替尼在无已知分子畸变的HES和CEL中的有效性较低（n = 15）;在40%（6/15）的患者中观察到复发，2例患者在4.8和24.5个月后复发。3例患者死于与研究治疗无关的伊马替尼耐药进展性CEL（n = 2）或心肌梗死（n = 1）。总体而言，伊马替尼耐受性良好，III/IV级毒性发生率低。这些数据证实了伊马替尼对PDGFR重排的CEL患者的长期疗效，也表明少数没有已知分子畸变的HES病例可能从伊马替尼中获益。
This study evaluated the efficacy and safety of imatinib in chronic eosinophilic leukaemia (CEL, n = 23) and hypereosinophilic syndrome (HES, n = 13). In CEL with FIP1L1-PDGFRA (n = 16) or various PDGFRB fusion genes (n = 5), complete haematological remission (CHR) was achieved in 95% (20/21) after 3 months. Complete molecular remission (CMR) was seen in 75% (12/16) of cases with FIP1L1-PDGFRA positive CEL by 6 months, and in 87% (13/15) after 12 months. CMR was achieved in three of five PDGFRB fusion positive patients after 3, 9 and 18 months respectively. All patients are currently on imatinib (100 mg; n = 13, 400 mg; n = 8) and no molecular relapse has yet been observed (median 26.7 months; range, 6.9-39.9). Imatinib was less effective in HES and CEL without known molecular aberration (n = 15); CHR was observed in 40% (6/15) of patients, two patients relapsed after 4.8 and 24.5 months. Three patients died due to imatinib-resistant progressive CEL (n = 2) or myocardial infarction (n = 1) unrelated to study treatment. Overall, imatinib was well tolerated with a low incidence of grade III/IV toxicities. These data confirmed the long-term efficacy of imatinib for PDGFR-rearranged CEL patients, and also showed that a minority of HES cases without known molecular aberrations may benefit from imatinib.