Giordano M, Danova M, Mazzini G, Gobbi P, Riccardi A
Department of Internal Medicine, Second Medical Clinic, University, Pavia, Italy.
Cancer. 1993 May 1;71(9):2739-45. doi: 10.1002/1097-0142(19930501)71:9<2739::aid-cncr2820710909>3.0.co;2-b.
The proliferative characteristics of acute nonlymphoblastic leukemia (ANLL) were studied in vivo, and data were correlated with response to chemotherapy and survival.
Sixty-five patients with untreated ANLL and 15 patients with solid tumors and normal bone marrow (BM) received 250 mg/m2 of bromodeoxyuridine (BUdR); bivariate flow cytometric (FCM) analysis then was used to measure cell BUdR incorporation and DNA content to obtain a complete set of kinetic parameters (i.e., BM BUdR-labeling index, DNA-synthesis time, potential doubling time [Tpot], and cell production rate). The percentage of blasts with positive results for proliferating cell nuclear antigen (PCNA) also was obtained by FCM analysis on the same BM samples, and these kinetic parameters were derived specifically for the ANLL proliferating compartment (growth fraction). Induction therapy, consisting of vincristine, arabinosylcytosine, and daunomycin, was administered subsequently to the patients with ANLL.
Overall ANLL proliferative activity was lower than normal myelopoiesis, and a short Tpot was found to be a favorable factor for achieving complete remission (CR), the duration of CR, and survival. When the growth fraction was considered, however, ANLL proliferative activity was higher and more like that of normal BM. The kinetic differences detected in the PCNA-positive cells of patients with CR and no response and those with CR and survival durations above and below the median values for the entire series were highly significant in univariate analysis and retained a strong independent prognostic value when multivariate analysis was performed.
These data show the clinical feasibility of a detailed study of cell kinetics by means of new FCM-based techniques and reinforce the clinical value of pretreatment proliferative activity in ANLL.
对急性非淋巴细胞白血病（ANLL）的增殖特性进行了体内研究，并将数据与化疗反应和生存率相关联。
65例未经治疗的ANLL患者和15例实体瘤且骨髓（BM）正常的患者接受了250mg/m²的溴脱氧尿苷（BUdR）；然后采用双变量流式细胞术（FCM）分析来测量细胞BUdR掺入量和DNA含量，以获得完整的动力学参数集（即BM BUdR标记指数、DNA合成时间、潜在倍增时间[Tpot]和细胞产生率）。通过对相同BM样本进行FCM分析，还获得了增殖细胞核抗原（PCNA）检测结果为阳性的原始细胞百分比，并且这些动力学参数是专门针对ANLL增殖区室（生长分数）得出的。随后对ANLL患者给予由长春新碱、阿糖胞苷和柔红霉素组成的诱导治疗。
总体而言，ANLL的增殖活性低于正常骨髓生成，并且发现短的Tpot是实现完全缓解（CR）、CR持续时间和生存的有利因素。然而，当考虑生长分数时，ANLL的增殖活性更高，更类似于正常BM。在CR与无反应以及CR且生存持续时间高于和低于整个系列中位数的患者的PCNA阳性细胞中检测到的动力学差异，在单变量分析中具有高度显著性，并且在进行多变量分析时保留了强大的独立预后价值。
这些数据表明通过基于FCM的新技术详细研究细胞动力学的临床可行性，并强化了ANLL预处理增殖活性的临床价值。
