The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study.
The selective use of AMSA following high-dose cytarabine in patients with acute myeloid leukaemia in relapse: a Leukemia Intergroup study.
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在急性髓系白血病复发患者中高剂量阿糖胞苷后选择性使用 AMSA：一项白血病组间研究。
DOI：
10.1111/j.1365-2141.1992.tb06427.x
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发表时间：
1992
影响因子：
6.5
通讯作者：
Raza,A
中科院分区：
文献类型：
--
作者：
Larson,RA;Day,RS;Azarnia,N;Bennett,JM;Browman,G;Goldberg,J;Gottlieb,A;Grunwald,H;Miller,K;Raza,A
总结：本临床试验旨在评估大剂量阿糖胞苷（ara-C）在治疗首次复发的成人急性髓性白血病（AML）中的作用。我们还检验了以下假设：选择性使用AMSA（100 mg/m2/d，第7、8和9天）将增加完全缓解（CR）率，此时白血病细胞在单独使用Ara-C（2-3 g/m2/12 h）6天后立即保留在骨髓中。在155例可评价反应的患者中，115例（74%）在第6天出现明显的细胞减少，未接受进一步诱导化疗;其中53例（45%）在一个疗程后达到CR，45例（38%）出现耐药疾病。36例（23%）在单独使用ara-C 6天后细胞减少不充分的患者被随机分配到没有进一步化疗（21例患者）或AMSA 3天（15例患者）。一个疗程后的CR率分别为14%和53%（P= 0.001）。抗病组分分别为76%和40%。在单变量分析中，第6天骨髓穿刺标本中白血病细胞的分数减少（P<0.0001）和第6天骨髓活检中测量的白血病细胞质量减少（P= 0.001）是实现CR与残留疾病的最强预测因子。中位缓解持续时间为5个月，但7例患者（10%）在30-92+个月后仍处于CR状态。在140例仅接受6天ara-C治疗的患者中，治疗前白蛋白（P= 0.002）和乳酸脱氢酶（P= 0.01）水平是单变量分析中最强的反应预测因子，但在逐步logistic回归分析中，只有白蛋白仍具有显著性（P= 0.01）。白蛋白> 4.0mg/dl、LDH <125%的患者CR率为71%，耐药率仅为16%。在缺乏这两个有利特征的患者中，只有38%的患者获得CR，39%的患者患有耐药疾病。因此，治疗前特征和第6天骨髓样本中的快速细胞减少确定了首次复发的AML患者的有利子集，其中一些人对6天单独的ara-C反应良好，并且长期无疾病缓解。
Summary.This clinical trial was designed to evaluate the role of high‐dose cytarabine (ara‐C) in the treatment of adults with acute myeloid leukaemia (AML) in first relapse. We also tested the hypothesis that the selective use of AMSA (100 mg/m2/d on days 7, 8 and 9) would increase the complete remission (CR) rate when leukaemia cells remained in the bone marrow immediately following 6 d of Ara‐C (2–3 g/m2/12 h) alone. Of 155 patients evaluable for response, 115 (74%) experienced marked cytoreduction by day 6 and received no further induction chemotherapy; 53 (45%) of these patients achieved CR after one course and 45 (38%) had resistant disease. The 36 patients (23%) with inadequate cytoreduction after the 6 d of ara‐C alone were randomly assigned either to no further chemotherapy (21 patients) or to 3 d of AMSA (15 patients). The CR rates after one course were 14% and 53%, respectively (P= 0001). and the fractions with resistant disease were 76% and 40%, respectively. The fractional reduction of leukaemia cells in the day 6 bone marrow aspirate specimen (P<0.0001) and the reduction in the leukaemia cell mass measured in the day 6 marrow biopsy (P= 0.001) were the strongest predictors for achieving CR versus having residual disease in univariate analyses. The median duration of remission was 5 months, but seven patients (10%) remain in CR after 30–92+ months. Among the 140 patients who received only the 6 d of ara‐C, the pretreatment albumin (P= 0.002) and lactate dehydrogenase (P= 0.01) levels were the strongest predictors of response in univariate analyses, but only the albumin remained significant (P= 0.01) in a stepwise logistic regression analysis. Those patients with albumin >4.0 mg/dl and LDH <125% of normal had a 71% CR rate, and only 16% had resistant disease. Among patients lacking both of these favourable characteristics, only 38% had a CR and 39% had resistant disease. Thus, pretreatment characteristics and rapid cytoreduction in the day 6 bone marrow sample identified a favourable subset of patients with AML in first relapse, some of whom responded quite well to 6 d of ara‐C alone and have had long disease‐free remissions.