Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders
Results of imatinib mesylate therapy in patients with refractory or recurrent acute myeloid leukemia, high-risk myelodysplastic syndrome, and myeloproliferative disorders
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DOI：
10.1002/cncr.11416
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发表时间：
2003-06-01
期刊：
影响因子：
6.2
通讯作者：
Kantarjian, H
中科院分区：
文献类型：
--
作者：
Cortes, J;Giles, F;Kantarjian, H
背景资料。甲磺酸伊马替尼是c-abl、bcr/abl、c-kit和血小板衍生生长因子受体(PDGF-R)的选择性酪氨酸激酶抑制剂。C-KIT在大多数急性髓系白血病(AML)和骨髓增生异常综合征(MDS)患者中表达，PDGF参与了骨髓增生性疾病(MPD)的发病机制。48例AML(n=10)、MDS(n=8)、骨髓纤维化(n=18)、不典型慢性粒细胞白血病(CML；n；7)、慢性粒细胞白血病(CMML；n=3)、真性红细胞增多症(n=2)患者接受伊马替尼400 mg/d治疗。在骨髓纤维化患者中，14例脾肿大患者中有10例(71%)脾大小缩小30%或以上，1例三系血液学改善，2例红系血液学改善，1例血小板计数改善。1例不典型CML患者红系血液学改善。两名真性红细胞增多症患者需要的静脉采血次数都较少(从每年2-3次减少到8个月内不需要，从每年3-6次减少到9个月内1次)。三名CMML患者均无反应。治疗耐受性良好。副作用与CML患者相似。结论在这些疾病类型的小亚组中，单药伊马替尼对AML、MDS、不典型CML或无PDGF-R融合基因的CMML患者没有显著的临床疗效。关于真性红细胞增多症的初步数据是有希望的，值得进一步研究。骨髓纤维化患者的反应很轻微。因此，包括伊马替尼在内的联合治疗方案可能更有效。(C)2003年美国癌症协会。
BACKGROUND. Imatinib mesylate is a selective tyrosine kinase inhibitor of c-abl, bcr/abl, c-kit, and platelet-derived growth factor-receptor (PDGF-R). c-kit is expressed in most patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) and PDGF has been implicated in the pathogenesis of myeloproliferative disorders (MPD).METHODS. The authors investigated the efficacy of imatinib in patients with these disorders. Forty-eight patients with AML (n = 10), MDS (n = 8), myelofibrosis (n = 18), atypical chronic myeloid leukemia (CML; n 7), chronic myelomonocytic leukemia (CMML; n = 3), or polycythemia vera (n 2) were treated with imatinib 400 mg daily.RESULTS. None of the patients with AML or MDS responded. Among patients with myelofibrosis, 10 of 14 patients with splenomegaly (71%) had a 30% or greater reduction in spleen size, 1 patient had trilineage hematologic improvement, 2 had erythroid hematologic improvement, and 1 had improvement in platelet count. One patient with atypical CML had erythroid hematologic improvement. Both patients with polycythemia vera needed fewer phlebotomies (from 2-3 per year to none during the 8 months of therapy and from 3-6 per year to 1 during 9 months of therapy). None of the three patients with CMML responded. Treatment was well tolerated. The side effects were similar to those observed in patients with CML.CONCLUSIONS. Within these small subgroups of disease types, single-agent imatinib did not achieve a significant clinical response among patients with AML, MDS, atypical CML, or CMML without PDGF-R fusion genes. Preliminary data on polycythemia vera are promising and deserve further investigation. Responses among myelofibrosis patients were minor. Therefore, a combination treatment regimen including imatinib may be more effective. (C) 2003 American Cancer Society.