Quintas-Cardama Alfonso, Kantarjian Hagop, O'Brien Susan, Garcia-Manero Guillermo, Rios Mary B, Talpaz Moshe, Cortes Jorge
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2004 Jun 15;100(12):2592-7. doi: 10.1002/cncr.20285.
Imatinib mesylate administration has become standard treatment for patients with chronic myelogenous leukemia (CML). Although the safety profile of imatinib is favorable, Grade > or = 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria) occurs in 35-45% of patients with CML in chronic phase who receive standard-dose imatinib. Myelosuppression results in treatment interruptions, which may compromise responses to imatinib. The authors investigated the ability of granulocyte-colony-stimulating factor (filgrastim) to reverse imatinib-associated neutropenia, thereby allowing for more continuous imatinib administration.
Thirteen patients with chronic-phase CML and Grade > or = 3, imatinib-induced neutropenia were treated with filgrastim. Treatment with filgrastim was initiated after a median of 22 months from the start of imatinib. Eleven patients received filgrastim 5 microg/kg 1-3 times weekly, and 2 patients received filgrastim 5 microg/kg daily; doses were titrated to maintain an absolute neutrophil count (ANC) > or = 10(9)/L.
Seven of 11 patients (64%) who began treatment with an ANC < 1.5 x 10(9)/L had responses (i.e., their ANC improved to > or = 2 x 10(9)/L within 21 days); the other 4 patients experienced slower recovery but were able to continue receiving imatinib uninterrupted. Before filgrastim administration was initiated, patients did not receive imatinib (due to neutropenia-related treatment interruptions) for an average of 21% of the total time since the start of imatinib. This figure decreased to 6% after the start of filgrastim treatment (P = 0.0008). Before filgrastim treatment was initiated, only one patient had achieved a major (partial) cytogenetic response. After the start of filgrastim treatment, five patients had major cytogenetic responses (including two complete responses).
The authors concluded that filgrastim may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Some patients may experience improvements in their responses to therapy as a result.
甲磺酸伊马替尼给药已成为慢性粒细胞白血病（CML）患者的标准治疗方法。尽管伊马替尼的安全性良好，但接受标准剂量伊马替尼治疗的慢性期CML患者中，35% - 45%会出现≥3级中性粒细胞减少（根据美国国立癌症研究所通用毒性标准）。骨髓抑制导致治疗中断，这可能会影响对伊马替尼的反应。作者研究了粒细胞集落刺激因子（非格司亭）逆转伊马替尼相关中性粒细胞减少的能力，从而使伊马替尼能够更持续地给药。
13例慢性期CML且伊马替尼诱导的≥3级中性粒细胞减少患者接受非格司亭治疗。非格司亭治疗在伊马替尼开始使用中位数22个月后开始。11例患者每周接受1 - 3次5μg/kg的非格司亭治疗，2例患者每天接受5μg/kg的非格司亭治疗；剂量进行滴定以维持绝对中性粒细胞计数（ANC）≥10⁹/L。
11例开始治疗时ANC < 1.5×10⁹/L的患者中有7例（64%）有反应（即其ANC在21天内改善至≥2×10⁹/L）；其他4例患者恢复较慢，但能够继续不间断地接受伊马替尼治疗。在开始非格司亭给药之前，患者因中性粒细胞减少相关的治疗中断，在伊马替尼开始使用后的总时间里平均有21%的时间未接受伊马替尼治疗。非格司亭治疗开始后，这一数字降至6%（P = 0.0008）。在开始非格司亭治疗之前，只有1例患者达到主要（部分）细胞遗传学反应。非格司亭治疗开始后，5例患者有主要细胞遗传学反应（包括2例完全反应）。
作者得出结论，非格司亭可能克服伊马替尼相关的中性粒细胞减少，并使伊马替尼的给药得到改善。一些患者可能因此在治疗反应方面有所改善。
