Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia
Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia
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DOI：
10.1200/jco.2001.19.4.1040
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发表时间：
2001-02-15
影响因子：
45.3
通讯作者：
Sallan, SE
中科院分区：
文献类型：
--
作者：
Schwartz, CL;Thompson, EB;Sallan, SE
目的：探讨糖皮质激素在儿童急性淋巴细胞性白血病(ALL)中的应用是否存在剂量-反应关系。患者和方法：369例1~18岁的ALL患者在开始标准的多药诱导化疗前，随机分为四种不同剂量的糖皮质激素(强的松龙40 mg/m(2)/d或地塞米松6、18或150 mg/m(2)/d)，作为一个为期3天的单药窗口。3天后，通过骨髓原始细胞计数和外周血细胞绝对计数的减少来衡量皮质类固醇的药物反应。结果：随着地塞米松剂量的增加，骨髓原始细胞反应增强(P=0.007)，外周血原始细胞反应也呈类似趋势。大剂量糖皮质激素方案(地塞米松18或150 mg/m2/d)的疗效优于标准剂量的地塞米松或泼尼松(骨髓，P=0.002；外周原始细胞，P=0.05)。在接受标准剂量皮质激素治疗的患者中，耐药(EC-50和10(-7))外周原始细胞的有效率为38%，而敏感(EC-50和10(-7))外周原始细胞的有效率为92%(P=0.01)。相比之下，EC-50组在大剂量皮质类固醇治疗后没有出现差异反应。类似地，在标准剂量糖皮质激素方案后，外周血母细胞的反应与GCR之间存在关联，而在大剂量糖皮质激素方案后则不存在关联。大剂量皮质类固醇治疗消除了相对药物不敏感和低GCR对外周血母细胞的影响。
Purpose: We investigated whether there was a dose-response relationship for the use of corticosteroids in childhood acute lymphoblastic leukemia (ALL).Patients and Methods: Three hundred sixty-nine patients, ages 1 to 18 years with ALL, were randomly assigned to receive one of four different doses of corticosteroid (prednisolone 40 mg/m(2)/d or dexamethasone 6, 18, or 150 mg/m(2)/d) administered as a 3-day, single-drug window before initiation of standard, multidrug induction chemotherapy. Corticosteroid drug response was measured by reduction in bone marrow blast counts and absolute peripheral blast counts after 3 days. Glucocarticoid receptor (GCR) number and the effective concentration of dexamethasone resulting in a 50% reduction of leukemic cell viability in vitro (EC-50) were evaluated at days 0 and 3.Results: Increasing dexamethasone doses resulted in greater marrow blast response (P = .007), with a similar trend in peripheral-blood blast response. High-dose carticosteroid regimens (dexamethasone 18 or 150 mg/m2/d) elicited better responses than standard doses of dexamethasone or prednisone (bone marrow, P = .002; peripheral blasts, P = .05). Among patients treated with standard-dose corticosteroids, 38% with resistant (EC-50 > 10(-7)) peripheral blasts had a good response compared with 92% with sensitive (EC-50 < 10(-7)) peripheral blasts (P = .01). In contrast, there was no differential response according to EC-50 group after high-dose corticosteroids. Similarly, an association between response and GCR on peripheral-blood blasts was noted after standard-dose corticosteroid regimens but not after high-dose corticosteroid regimens.Conclusion: Response of ALL to glucacorticoid therapy increased with dose. Higher-dose corticosteroid treatment abrogated the effect of relative drug insensitivity and of low GCR on peripheral blasts.