Simon William, Segel George B, Lichtman Marshall A
Department of Biochemistry and Biophysics, University of Rochester School of Medicine, NY 14642, USA.
Blood Cells Mol Dis. 2006 Sep-Oct;37(2):116-24; discussion 125-7. doi: 10.1016/j.bcmd.2006.06.006. Epub 2006 Aug 10.
We have examined the role of early allogeneic hematopoietic stem cell transplantation in patients with chronic phase chronic myelogenous leukemia (CML) who enter a complete cytogenetic remission with imatinib mesylate. Three kinds of data were used to examine the effect of the outcome of current BCR-ABL inhibitor treatment compared to early allogeneic stem cell transplantation: (1) the life expectancy of the general population of the United States as a function of age, (2) the life expectancy of CML patients as a function of the age of patients treated with imatinib mesylate (imatinib) who achieve a complete cytogenetic remission, and (3) the life expectancy of patients with CML treated with matched-related or matched-unrelated stem cell transplantation as a function of age, derived from data provided by the Center for International Blood and Marrow Transplant Research (CIBMTR). We also considered separately the transplant results of the Fred Hutchinson Cancer Research Center (FHCRC), which are substantially better than the "average" outcome from the CIBMTR. We have calculated the projected life expectancy from the age at which patients with CML enter complete cytogenetic remission with imatinib and that of those who receive allogeneic stem cell transplantation. The outcome with imatinib therapy of newly diagnosed patients with CML has been documented for only 4 and 1/2 years, whereas transplant data were available for up to 25 years. Thus, in order to compare life expectancy and 10-year survival probability, it was necessary to extrapolate the imatinib data. A basis for extrapolation is offered and conservative estimates have been used for comparison. Our best estimate is that patients receiving imatinib who have a complete cytogenetic remission have a higher projected probability of 10-year survival than patients who are transplanted, based on results provided by the CIBMTR, and have about the same probability compared to the data from the Fred Hutchinson Cancer Center for patients in the 30- to 60-year-old range. The mathematical approach used here permits reexamining the analysis using future data on BCR-ABL inhibitor therapy or allogeneic stem cell transplantation therapy or both.
我们研究了早期异基因造血干细胞移植在慢性期慢性髓性白血病（CML）患者中的作用，这些患者使用甲磺酸伊马替尼后实现了完全细胞遗传学缓解。我们使用了三类数据来检验当前BCR-ABL抑制剂治疗结果与早期异基因干细胞移植相比的效果：（1）美国普通人群的预期寿命作为年龄的函数；（2）接受甲磺酸伊马替尼（伊马替尼）治疗且实现完全细胞遗传学缓解的CML患者的预期寿命作为患者年龄的函数；（3）接受匹配相关或匹配不相关干细胞移植的CML患者的预期寿命作为年龄的函数，数据来源于国际血液和骨髓移植研究中心（CIBMTR）。我们还分别考虑了弗雷德·哈钦森癌症研究中心（FHCRC）的移植结果，该中心的结果明显优于CIBMTR的“平均”结果。我们计算了CML患者使用伊马替尼实现完全细胞遗传学缓解时的年龄以及接受异基因干细胞移植患者的预期寿命。新诊断的CML患者接受伊马替尼治疗的结果仅记录了4年半，而移植数据的时间跨度长达25年。因此，为了比较预期寿命和10年生存概率，有必要对伊马替尼数据进行外推。我们提供了外推的依据，并使用保守估计进行比较。根据CIBMTR提供的结果，我们的最佳估计是，实现完全细胞遗传学缓解的接受伊马替尼治疗的患者10年生存的预测概率高于接受移植的患者；对于30至60岁的患者，与弗雷德·哈钦森癌症中心的数据相比，两者的概率大致相同。这里使用的数学方法允许使用未来关于BCR-ABL抑制剂治疗或异基因干细胞移植治疗或两者的数据重新审视该分析。
