Kantarjian H M, Barlogie B, Keating M J, Hall R R, Smith T L, McCredie K B, Freireich E J
J Clin Invest. 1985 Jul;76(1):319-24. doi: 10.1172/JCI111964.
To determine the clinical and biologic relevance of cellular kinetics in leukemia, DNA flow cytometric analysis was performed on bone marrow biopsy specimens from 148 previously untreated adult patients with acute myelogenous leukemia. The proportion of cells in synthesis, second growth, and mitosis (S + G2M) ranged from 4% to 33% with a median of 14%. The overall incidence of complete remission was not affected by the pretreatment cell cycle distribution. As in earlier studies, there was a marked decline in remission rate with advancing age from 73% for patients age less than or equal to 50 yr to 50% for those greater than 50 (P less than 0.01). Although not affecting remission induction overall, an increasing proportion of cells in S + G2M phase was favorable in patients under the age of 50 yr, but was associated with a progressive decline in remission rate in older patients (P = 0.01). This age-related divergent effect of cell cycle kinetics on initial response to therapy was confined to the less favorable subgroup of patients with karyotypic abnormalities, whereas patients with normal diploid cytogenetics had a consistently higher response rate regardless of proliferative activity. A positive correlation was also observed between percent of S + G2M cells and the proportion of diploid metaphases in young patients, contrasting with a negative correlation in the older age group. Our observations strongly suggest that the well-recognized prognostic effect of age on remission induction is not entirely host-mediated, but is at least partly an expression of disease-intrinsic differences between young and older patients.
为了确定白血病细胞动力学的临床和生物学相关性，对148例未经治疗的成年急性髓性白血病患者的骨髓活检标本进行了DNA流式细胞术分析。处于合成期、第二生长期和有丝分裂期（S + G2M）的细胞比例为4%至33%，中位数为14%。完全缓解的总体发生率不受预处理细胞周期分布的影响。与早期研究一样，随着年龄增长，缓解率显著下降，年龄小于或等于50岁的患者为73%，大于50岁的患者为50%（P < 0.01）。虽然总体上不影响缓解诱导，但S + G2M期细胞比例增加对50岁以下患者有利，但与老年患者的缓解率逐渐下降相关（P = 0.01）。细胞周期动力学对治疗初始反应的这种年龄相关的不同影响仅限于核型异常的预后较差亚组患者，而正常二倍体细胞遗传学的患者无论增殖活性如何，缓解率始终较高。在年轻患者中，还观察到S + G2M细胞百分比与二倍体中期比例之间呈正相关，而在老年组中呈负相关。我们的观察结果强烈表明，年龄对缓解诱导的公认预后影响并非完全由宿主介导，至少部分是年轻和老年患者疾病内在差异的表现。
