Kantarjian H M, Keating M J, Talpaz M, Walters R S, Smith T L, Cork A, McCredie K B, Freireich E J
Department of Hematology, University of Texas M.D. Anderson Hospital and Tumor Institute at Houston.
Am J Med. 1987 Sep;83(3):445-54. doi: 10.1016/0002-9343(87)90754-6.
Two hundred forty-two patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant biologic and prognostic associations. Twenty percent of patients had lymphoid blast crisis. Clonal evolution was present in 60 percent of patients at blast crisis and involved most frequently the development of a double Philadelphia chromosome, trisomy 8, or isochromosome 17. The overall median survival from blast crisis was 18 weeks. Patient characteristics demonstrated to have significant association with short survival were: anemia; thrombocytopenia; myeloid or undifferentiated blast cell morphology; clonal evolution involving the presence of a double Philadelphia chromosome, trisomy 8, or isochromosome 17; and low marrow blast percentage. Of 195 patients who received therapy for blast crisis, complete remission was achieved in 44 (23 percent) patients, and 24 (13 percent) patients had a partial remission or hematologic improvement. Lower complete remission rates were associated with old age, thrombocytopenia, myeloid or undifferentiated blast cell morphology, clonal evolution--especially isochromosome 17 and trisomy 8--and long interval from diagnosis to onset of blast crisis. A multivariate analysis identified two characteristics to have independent prognostic importance for both survival and remission: platelet counts and blast cell morphology. In addition, clonal evolution had additive prognostic value for survival (double Philadelphia chromosome) and for response (isochromosome 17). The beneficial association of therapy with survival was demonstrated by the significantly longer median survival of patients treated since 1981 compared with those treated earlier, even after accounting for the pretreatment prognostic factors, and by the significant improvement in survival of patients achieving remission using the "landmark" analysis technique.
对242例处于急变期的费城染色体阳性慢性髓性白血病患者进行了回顾性研究，以确定显著的生物学和预后相关性。20%的患者为淋巴细胞急变期。60%的患者在急变期出现克隆演变，最常见的是双费城染色体、8号染色体三体或17号等臂染色体的出现。急变期后的总体中位生存期为18周。与生存期短显著相关的患者特征包括：贫血；血小板减少；髓系或未分化原始细胞形态；涉及双费城染色体、8号染色体三体或17号等臂染色体的克隆演变；以及低骨髓原始细胞百分比。在195例接受急变期治疗的患者中，44例（23%）患者达到完全缓解，24例（13%）患者部分缓解或血液学改善。完全缓解率较低与老年、血小板减少、髓系或未分化原始细胞形态、克隆演变（尤其是17号等臂染色体和8号染色体三体）以及从诊断到急变期发作的间隔时间长有关。多因素分析确定了两个特征对生存和缓解具有独立的预后重要性：血小板计数和原始细胞形态。此外，克隆演变对生存（双费城染色体）和反应（17号等臂染色体）具有附加预后价值。自1981年以来接受治疗的患者中位生存期明显长于早期治疗的患者，即使在考虑了预处理预后因素之后，以及使用“标志性”分析技术实现缓解的患者生存期显著改善，均表明治疗与生存之间存在有益关联。
