Raza A, Preisler H, Lampkin B, Lykins J, Kukla C, Gartside P, Sheikh Y, Yousuf N, White M, Barcos M
Roswell Park Memorial Institute, Buffalo, New York.
Am J Hematol. 1993 Feb;42(2):147-57. doi: 10.1002/ajh.2830420202.
Bromodeoxyuridine (BrdU) was administered to 86 newly diagnosed patients with standard risk acute myeloid leukemia (AML) prior to starting induction therapy and the labeling index (LI), durations of S-phase (Ts), and the cell cycle (Tc) of myeloblasts were determined. Induction therapy with cytosine arabinoside and daunomycin was subsequently started. Bone marrow biopsies were obtained on days 6 and 17 and weekly thereafter, and were treated with a monoclonal anti-BrdU antibody to determine the fate of cells labeled on day 0 by BrdU. BrdU labeled granulocytes indicating the presence of in vivo differentiation (Diff+) were identified in 48 patients ranging from 1+ (1-10 labeled cells) to 4+ (greater than 31 labeled granulocytes). When compared to 38 differentiation negative (Diff-) patients, Diff+ group had longer Ts (14.5 hr vs. 10.95 hr, P = 0.015) and Tc (59.7 hr vs. 41.7 hr, P = 0.017). Remission duration was significantly longer (no median) for 3-4+ Diff+ as compared to Diff- (median = 220 days) patients (Wilcoxon P = 0.04). We conclude that the detection of in vivo differentiation in AML patients indicates a favorable long-term prognosis either due to the presence of a substantial amount of normal residual hematopoiesis prior to starting induction therapy or due to the ability of leukemic cells to undergo differentiation.
在开始诱导治疗前,对86例新诊断的标准风险急性髓系白血病(AML)患者给予溴脱氧尿苷(BrdU),并测定其标记指数(LI)、髓母细胞的S期持续时间(Ts)和细胞周期(Tc)。随后开始用阿糖胞苷和柔红霉素进行诱导治疗。在第6天和第17天以及此后每周进行骨髓活检,并用单克隆抗BrdU抗体处理,以确定在第0天被BrdU标记的细胞的命运。在48例患者中鉴定出BrdU标记的粒细胞,表明存在体内分化(Diff+),范围从1+(1 - 10个标记细胞)到4+(大于31个标记粒细胞)。与38例分化阴性(Diff-)患者相比,Diff+组的Ts更长(14.5小时对10.95小时,P = 0.015),Tc更长(59.7小时对41.7小时,P = 0.017)。与Diff-患者(中位数 = 220天)相比,3 - 4+ Diff+患者的缓解期明显更长(无中位数)(Wilcoxon P = 0.04)。我们得出结论,AML患者体内分化的检测表明长期预后良好,这要么是因为在开始诱导治疗前存在大量正常残余造血,要么是因为白血病细胞具有分化能力。