Quintás-Cardama Alfonso, Kantarjian Hagop, Ravandi Farhad, O'Brien Susan, Thomas Deborah, Vidal-Senmache Gabriela, Wierda William, Kornblau Steven, Cortes Jorge
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2009 Jun 1;115(11):2482-90. doi: 10.1002/cncr.24257.
The most frequent nonhematologic side effects associated with dasatinib therapy in patients with chronic myeloid leukemia (CML) are gastrointestinal, rash, and fluid retention syndromes. However, bleeding has been observed in some patients receiving dasatinib. In the current study, the authors investigated the risk factors and management of bleeding associated with dasatinib therapy for CML after imatinib failure.
The bleeding episodes associated with dasatinib therapy in 138 patients with CML who were consecutively treated at the study institution in clinical trials were evaluated.
Bleeding occurred in 32 (23%) patients (grade >or=3 in 9 [7%] patients [according to National Cancer Institute Common Toxicity Criteria]), including in 12% of patients treated in chronic phase, 31% of patients treated in accelerated phase (AP), and 35% of patients treated in blast phase (BP) (P = .02). The majority of episodes (81%) affected the gastrointestinal tract. Basic coagulation studies were normal in 97% of patients who developed bleeding complications. Although 37% of episodes occurred with platelet counts >100 x 10(9)/L, multivariate analysis identified thrombocytopenia and advanced phase CML as risk factors for bleeding. A trend toward an increased risk with a twice-daily schedule was observed (P = .17). Management included dasatinib interruption for a median of 17 days (range, 3-51 days) in 47%, of patients and transfusions in 72% of patients.
Bleeding occurs during dasatinib therapy, particularly in patients with AP or BP disease and low platelet counts. Appropriate clinical monitoring and the timely interruption of dasatinib therapy are warranted in this subset of patients.
慢性髓性白血病（CML）患者接受达沙替尼治疗时，最常见的非血液学副作用是胃肠道反应、皮疹和液体潴留综合征。然而，在一些接受达沙替尼治疗的患者中观察到了出血情况。在本研究中，作者调查了伊马替尼治疗失败后达沙替尼治疗CML相关出血的危险因素及处理措施。
对在研究机构连续接受临床试验治疗的138例CML患者中与达沙替尼治疗相关的出血事件进行了评估。
32例（23%）患者发生出血（根据美国国立癌症研究所通用毒性标准，9例[7%]患者为3级及以上），其中慢性期治疗的患者中有12%发生出血，加速期（AP）治疗的患者中有31%发生出血，急变期（BP）治疗的患者中有35%发生出血（P = 0.02）。大多数出血事件（81%）累及胃肠道。发生出血并发症的患者中97%的基础凝血检查正常。虽然37%的出血事件发生在血小板计数>100×10⁹/L时，但多因素分析确定血小板减少和CML晚期为出血的危险因素。观察到每日两次给药方案有增加出血风险的趋势（P = 0.17）。处理措施包括47%的患者中断达沙替尼治疗，中位时间为17天（范围3 - 51天），72%的患者接受输血治疗。
达沙替尼治疗期间会发生出血，尤其是AP或BP期疾病且血小板计数低的患者。对于这部分患者，进行适当的临床监测并及时中断达沙替尼治疗是必要的。
