Emergence of clonal chromosomal abnormalities in Philadelphia negative hematopoiesis in chronic myeloid leukemia patients treated with nilotinib after failure of imatinib therapy.
Emergence of clonal chromosomal abnormalities in Philadelphia negative hematopoiesis in chronic myeloid leukemia patients treated with nilotinib after failure of imatinib therapy.
复制标题
DOI：
10.1016/j.leukres.2009.05.010
复制
发表时间：
2009-12
影响因子：
2.7
通讯作者：
Carmen Baldazzi;S. Luatti;G. Marzocchi;Monica Stacchini;C. Gamberini;F. Castagnetti;F. Palandri;G. Rosti;M. Baccarani;N. Testoni
中科院分区：
文献类型：
--
作者：
Carmen Baldazzi;S. Luatti;G. Marzocchi;Monica Stacchini;C. Gamberini;F. Castagnetti;F. Palandri;G. Rosti;M. Baccarani;N. Testoni
在伊马替尼治疗慢性粒细胞白血病（CML）患者期间，广泛观察到费城阴性（Ph−）中期细胞克隆性细胞遗传学异常（CA）[1，2]。最近，已经描述了在伊马替尼治疗失败后接受达沙替尼治疗的一些CML患者中出现这种异常[3，4]。据我们所知，仅1例患者在伊马替尼治疗后尼洛替尼治疗期间报告Ph−克隆细胞遗传学异常[5]。第二代酪氨酸激酶抑制剂（TKI）治疗期间Ph−细胞CA的发生率和后果应进行广泛研究;这个问题值得特别关注，因为这些新药对白血病和残留正常造血的压力远高于伊马替尼。在我们的研究所，我们分析了30例晚期慢性期（CP）CML患者在伊马替尼治疗失败后，通过常规细胞遗传学（CC）和荧光原位杂交（FISH）进行尼洛替尼治疗。在诊断时、伊马替尼治疗期间、开始尼洛替尼治疗前和尼洛替尼治疗第一年期间每3-6个月进行一次骨髓（BM）细胞遗传学分析;此后每12个月或在疾病进展的情况下进行一次骨髓细胞遗传学分析。使用DNA商业探针进行FISH。诊断时，使用LSI双色双融合BCR-ABL DNA探针（Vysis，Downers格罗夫，IL，美国）表征BCR-ABL重排。根据CC的结果，使用适当的探针进行后续分析。患者为18名女性和12名男性，中位年龄为51岁（范围18-77）。伊马替尼治疗的中位时间为34个月（范围7-71）。14例患者仅接受伊马替尼作为既往治疗，而16例患者接受了其他治疗，如：羟基脲，干扰素，胞嘧啶核苷，白消安。在尼洛替尼治疗期间，18例（60%）患者在中位时间4.7个月（范围1-10）内实现了完全细胞遗传学缓解（CCyR）。在开始尼洛替尼治疗后，对患者进行了中位18个月（范围4-42）的随访（表1）。
Clonal cytogenetic abnormalities (CAs) in Philadelphia negative (Ph−) metaphases have been widely observed during imatinib treatment in patients with chronic myeloid leukemia (CML)[1, 2]. Recently, the appearance of such abnormalities in some CML patients, treated with dasatinib after imatinib failure, has been described [3, 4]. To the best of our knowledge, only one patient has been reported to develop a cytogenetic abnormality in Ph− clone during nilotinib treatment, following imatinib [5]. The incidence and consequences of CAs in Ph− cells during treatment with second generation tyrosine kinase inhibitors (TKIs) should be extensively investigated; this issue, deserves a particular attention, since these new drugs put a far higher pressure on the leukemic and the residual normal hematopoiesis than imatinib. At our institute we analyzed 30 late chronic phase (CP) CML patients treated with nilotinib after imatinib failure by conventional cytogenetic (CC) and fluorescence in situ hybridization (FISH). Cytogenetic analysis of bone marrow (BM) was performed at diagnosis, during imatinib treatment, before starting nilotinib and every 3–6 months during the first year of nilotinib therapy; thereafter every 12 months or in case of disease progression. FISH was performed using DNA commercial probes. At diagnosis LSI Dual Color Dual Fusion BCR-ABL DNA probe (Vysis, Downers Grove, IL, USA) was used to characterize BCR-ABL rearrangement. The subsequent analysis was performed using appropriate probes, depending on the results of CC.The patients were 18 females and 12 males, median age was 51 years (range 18–77). The median time of imatinib therapy was 34 months (range 7–71). Fourteen patients received only imatinib as previous therapy, whereas 16 patients were treated with additional therapies, such as: hydroxyurea, interferon-, cytosinearabinoside, busulphan. During nilotinib therapy 18 (60%) patients achieved a complete cytogenetic response (CCyR), within a median time of 4.7 months (range 1–10). Patients were followed for a median time of 18 months (range 4–42) after commencing nilotinib therapy (Table 1).