Angstreich Greg R, Smith B Douglas, Jones Richard J
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Bunting-Blaustein Cancer Research Building, 1650 Orleans Street, Room 207, Baltimore, MD 21231, USA.
Curr Opin Oncol. 2004 Mar;16(2):95-9. doi: 10.1097/00001622-200403000-00002.
This review considers recent developments in the treatment of chronic myeloid leukemia with attention to current data evaluating the relative roles of imatinib mesylate, interferon-alpha, and allogeneic blood or marrow transplantation. Additionally, the review discusses advances in the basic understanding of the mechanisms by which these three different therapies function against chronic myeloid leukemia.
Long-term follow-up has found that interferon-alpha was able to produce complete cytogenetic remission in15 to 25% of patients, with some of these patients achieving a molecular remission. Some patients who achieve a complete cytogenetic remission also achieve long-term disease-free survival and possibly cure. Imatinib has produced remarkable hematologic and cytogenetic responses in newly treated and in interferon-alpha-refractory patients, yet there are no long-term survival data at this point. Some laboratory findings imply that imatinib may primarily affect mature chronic myeloid leukemia progenitors and not chronic myeloid leukemia stem cells, leaving doubt that the improved rate of complete cytogenetic remissions will result in increased overall survival. Other clonal cytogenetic abnormalities have also been reported in the Philadelphia chromosome-negative cells present in complete cytogenetic remissions to imatinib. The use of donor lymphocytes infusion (DLI) continues to treat relapsed chronic myeloid leukemia effectively after allogeneic blood or marrow transplantation whereas the use of nonmyeloablative therapy has effectively reduced transplant-related mortality.
Patients with chronic myeloid leukemia now have several potential treatment options from which to choose. Imatinib mesylate currently provides excellent hematologic and cytogenetic response rates with minimal toxicity. However, long-term data of efficacy is lacking. Emerging evidence that imatinib rarely leads to molecular complete remission and that many patients are still at risk of relapse and other clonal disorders is concerning and suggest the possibility that imatinib's early high response rates may not translate into survival advantage. Interferon-alpha continues to be effective therapy for many patients and, along with blood or marrow transplantation, is proved to prolong survival. The impacts of both are in part limited because of their toxicity profiles. Ongoing laboratory investigations and clinical trials remain paramount to providing the best treatment approach for our patients with chronic myeloid leukemia.
本综述探讨慢性髓性白血病治疗的最新进展，重点关注评估甲磺酸伊马替尼、α干扰素以及异基因血液或骨髓移植相对作用的当前数据。此外，还讨论了对这三种不同疗法针对慢性髓性白血病发挥作用机制的基础认识进展。
长期随访发现，α干扰素能够使15%至25%的患者实现完全细胞遗传学缓解，其中部分患者达到分子学缓解。一些实现完全细胞遗传学缓解的患者也实现了长期无病生存甚至可能治愈。伊马替尼在初治患者及α干扰素难治性患者中产生了显著的血液学和细胞遗传学反应，但目前尚无长期生存数据。一些实验室研究结果表明，伊马替尼可能主要影响成熟的慢性髓性白血病祖细胞，而非慢性髓性白血病干细胞，这使得完全细胞遗传学缓解率的提高是否会带来总生存率的增加存疑。在伊马替尼治疗后达到完全细胞遗传学缓解的费城染色体阴性细胞中，也报道了其他克隆性细胞遗传学异常。异基因血液或骨髓移植后，供体淋巴细胞输注（DLI）继续有效治疗复发的慢性髓性白血病，而非清髓性疗法有效降低了移植相关死亡率。
慢性髓性白血病患者现在有多种潜在治疗选择。甲磺酸伊马替尼目前提供了优异的血液学和细胞遗传学反应率，且毒性极小。然而，缺乏疗效的长期数据。新出现的证据表明，伊马替尼很少导致分子学完全缓解，许多患者仍有复发和其他克隆性疾病的风险，这令人担忧，并提示伊马替尼早期的高反应率可能无法转化为生存优势。α干扰素对许多患者仍然是有效的治疗方法，并且与血液或骨髓移植一样，被证明可延长生存期。两者的影响部分受到其毒性特征的限制。正在进行的实验室研究和临床试验对于为慢性髓性白血病患者提供最佳治疗方法仍然至关重要。
