Nussenzveig Roberto H, Cortes Jorge, Sever Matjaz, Quintás-Cardama Alfonso, Ault Pat, Manshouri Taghi, Bueso-Ramos Carlos, Prchal Josef T, Kantarjian Hagop, Verstovsek Srdan
Department of Leukemia, M.D. Anderson Cancer Center, Box 428, 1515 Holcombe Boulevard, Houston, TX, 77030, USA.
ARUP Laboratories, Salt Lake City, UT, USA.
Int J Hematol. 2009 Jul;90(1):58-63. doi: 10.1007/s12185-009-0345-y. Epub 2009 May 30.
Polycythemia vera (PV) is a chronic myeloproliferative neoplasm (MPN) characterized by excessive production of red blood cells. Patients with PV are at a risk of thrombosis, bleeding, and transformation to myelofibrosis or acute myeloid leukemia. Therapy for PV is based on the use of phlebotomy, aspirin, and in high-risk patients, cytoreductive agents such as hydroxyurea. Anecdotal evidence suggests that imatinib mesylate, a selective tyrosine kinase inhibitor of ABL1, ARG, PDGFR, and KIT kinases has activity in PV. We conducted an open-label phase II clinical trial of imatinib at the standard dose of 400 mg daily in 24 patients with PV. The median duration of imatinib therapy was 5.1 months (range 0.2-86.4). Overall, 4 (17%) patients responded: one had a complete and three partial hematological response. The median time to response was 17.5 months (range 6-28), and the median duration of response was 17 months (range 9-68). No significant changes in JAK2(V617F) mutation burden were noted during imatinib therapy when compared with pretreatment values (P = 0.46). Therapy with imatinib was generally well tolerated. Our data indicate that imatinib has minimal clinical activity in PV.
真性红细胞增多症（PV）是一种慢性骨髓增殖性肿瘤（MPN），其特征是红细胞过度生成。PV患者有发生血栓形成、出血以及转化为骨髓纤维化或急性髓系白血病的风险。PV的治疗基于放血疗法、阿司匹林的使用，对于高危患者，则使用细胞减灭剂如羟基脲。轶事证据表明，甲磺酸伊马替尼，一种ABL1、ARG、PDGFR和KIT激酶的选择性酪氨酸激酶抑制剂，在PV中具有活性。我们对24例PV患者进行了一项开放标签的II期临床试验，使用标准剂量每日400 mg的伊马替尼。伊马替尼治疗的中位持续时间为5.1个月（范围0.2 - 86.4个月）。总体而言，4例（17%）患者有反应：1例完全缓解，3例部分血液学缓解。中位反应时间为17.5个月（范围6 - 28个月），中位缓解持续时间为17个月（范围9 - 68个月）。与治疗前值相比，伊马替尼治疗期间JAK2（V617F）突变负荷无显著变化（P = 0.46）。伊马替尼治疗一般耐受性良好。我们的数据表明，伊马替尼在PV中的临床活性极小。
