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α干扰素治疗慢性粒细胞白血病的细胞遗传学及荧光原位杂交评估

A cytogenetic and fluorescence in situ hybridization evaluation of interferon-alpha in the treatment of chronic myeloid leukemia.

作者信息

Itoh T, Tamura S, Takemoto Y, Kakishita E

机构信息

Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.

出版信息

Int J Mol Med. 1999 Dec;4(6):659-63. doi: 10.3892/ijmm.4.6.659.

DOI:10.3892/ijmm.4.6.659
PMID:10567680
Abstract

The effect of interferon-alpha (IFN) for chronic myeloid leukemia (CML) in the chronic phase (CP) was retrospectively evaluated in comparison with that of busulfan (BU) or hydroxyurea (HU) given alone. Among 107 patients diagnosed with CML between 1982 and 1997, 72 CP cases evaluable for long-term follow-up included 13 patients treated with BU alone, 18 with HU alone, and 41 with IFN-based therapy. Complete cytogenetic response (CCR) was achieved in 4/41 IFN cases (10%), and partial or minimal cytogenetic response occurred in 18/41 IFN cases (44%). In contrast, no cytogenetic response (NCR) was achieved in any BU or HU case. IFN treatment for 6 to 60 months was needed to achieve CCR. Overall survival curves revealed that the IFN group had significantly better survival than BU and HU groups (p=0.008 and 0.04, respectively). A significant correlation was found between karyotypic findings and fluorescence in situ hybridization (FISH) analyses in IFN-treated cases (r=0.739, p=0.0001). In some cases, however, the two methods showed discrepancy; BCR/ABL-positive cells represented only 20-75% of interphase bone marrow cells in NCR cases, although all metaphases examined were positive for the Philadelphia chromosome (Ph). A discrepancy was also seen in CCR cases; up to 22% of cells assessed were BCR/ABL-positive. These findings suggest that IFN is a useful therapy for CML in CP, and may have a suppressive effect on the CML clone even in NCR cases. The results also indicate that a combination of FISH and cytogenetic analyses may provide more detailed information for evaluating the efficacy of IFN than conventional cytogenetics alone.

摘要

回顾性评估了α干扰素(IFN)对慢性期慢性髓性白血病(CML)的疗效,并与单独使用白消安(BU)或羟基脲(HU)的疗效进行比较。在1982年至1997年间确诊为CML的107例患者中,72例可进行长期随访的慢性期病例包括13例单独接受BU治疗的患者、18例单独接受HU治疗的患者以及41例接受基于IFN治疗的患者。41例IFN治疗病例中有4例(10%)达到完全细胞遗传学缓解(CCR),18例(44%)出现部分或微小细胞遗传学缓解。相比之下,任何BU或HU治疗病例均未达到细胞遗传学缓解(NCR)。达到CCR需要进行6至60个月的IFN治疗。总体生存曲线显示,IFN组的生存率显著高于BU组和HU组(p值分别为0.008和0.04)。在IFN治疗的病例中,核型分析结果与荧光原位杂交(FISH)分析之间存在显著相关性(r = 0.739,p = 0.0001)。然而,在某些情况下,这两种方法结果存在差异;在NCR病例中,尽管所有检测的中期细胞费城染色体(Ph)均为阳性,但间期骨髓细胞中BCR/ABL阳性细胞仅占20%至75%。在CCR病例中也存在差异;高达22%的评估细胞为BCR/ABL阳性。这些发现表明,IFN是慢性期CML的一种有效治疗方法,即使在NCR病例中也可能对CML克隆有抑制作用。结果还表明,与单独的传统细胞遗传学相比,FISH和细胞遗传学分析相结合可能为评估IFN疗效提供更详细的信息。

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