Hughes Tim P, Kaeda Jaspal, Branford Susan, Rudzki Zbigniew, Hochhaus Andreas, Hensley Martee L, Gathmann Insa, Bolton Ann E, van Hoomissen Iris C, Goldman John M, Radich Jerald P
Institute of Medical and Veterinary Science, Adelaide, SA, Australia.
N Engl J Med. 2003 Oct 9;349(15):1423-32. doi: 10.1056/NEJMoa030513.
In a randomized trial, 1106 patients with chronic myeloid leukemia (CML) in chronic phase were assigned to imatinib or interferon alfa plus cytarabine as initial therapy. We measured levels of BCR-ABL transcripts in the blood of all patients in this trial who had a complete cytogenetic remission.
Levels of BCR-ABL transcripts were measured by a quantitative real-time polymerase-chain-reaction assay. Results were expressed relative to the median level of BCR-ABL transcripts in the blood of 30 patients with untreated CML in chronic phase.
In patients who had a complete cytogenetic remission, levels of BCR-ABL transcripts after 12 months of treatment had fallen by at least 3 log in 57 percent of those in the imatinib group and 24 percent of those in the group given interferon plus cytarabine (P=0.003). On the basis of the rates of complete cytogenetic remission of 68 percent in the imatinib group and 7 percent in the group given interferon plus cytarabine at 12 months, an estimated 39 percent of all patients treated with imatinib but only 2 percent of all those given interferon plus cytarabine had a reduction in BCR-ABL transcript levels of at least 3 log (P<0.001). For patients who had a complete cytogenetic remission and a reduction in transcript levels of at least 3 log at 12 months, the probability of remaining progression-free was 100 percent at 24 months, as compared with 95 percent for such patients with a reduction of less than 3 log and 85 percent for patients who were not in complete cytogenetic remission at 12 months (P<0.001).
The proportion of patients with CML who had a reduction in BCR-ABL transcript levels of at least 3 log by 12 months of therapy was far greater with imatinib treatment than with treatment with interferon plus cytarabine. Patients in the imatinib group with this degree of molecular response had a negligible risk of disease progression during the subsequent 12 months.
在一项随机试验中，1106例慢性期慢性髓性白血病（CML）患者被分配接受伊马替尼或干扰素α加阿糖胞苷作为初始治疗。我们测量了该试验中所有获得完全细胞遗传学缓解的患者血液中的BCR-ABL转录本水平。
采用定量实时聚合酶链反应测定法测量BCR-ABL转录本水平。结果以相对于30例未经治疗的慢性期CML患者血液中BCR-ABL转录本的中位数水平表示。
在获得完全细胞遗传学缓解的患者中，伊马替尼组57%的患者在治疗12个月后BCR-ABL转录本水平下降至少3个对数，干扰素加阿糖胞苷组为24%（P=0.003）。基于伊马替尼组12个月时68%的完全细胞遗传学缓解率和干扰素加阿糖胞苷组7%的缓解率，估计接受伊马替尼治疗的所有患者中有39%的BCR-ABL转录本水平降低至少3个对数，而接受干扰素加阿糖胞苷治疗的所有患者中只有2%（P<0.001）。对于在12个月时获得完全细胞遗传学缓解且转录本水平降低至少3个对数的患者，24个月时无进展的概率为100%，而转录本水平降低少于3个对数的此类患者为95%，12个月时未获得完全细胞遗传学缓解的患者为85%（P<0.001）。
与干扰素加阿糖胞苷治疗相比，伊马替尼治疗使治疗12个月时BCR-ABL转录本水平降低至少3个对数的CML患者比例要高得多。伊马替尼组中具有这种分子反应程度的患者在随后12个月内疾病进展的风险可忽略不计。
