Fredly Hanne, Stapnes Bjørnsen Camilla, Gjertsen Bjørn Tore, Bruserud Øystein
Section for Hematology, Institute of Medicine and Dentistry, University of Bergen, Bergen, Norway.
Hematology. 2010 Oct;15(5):338-43. doi: 10.1179/102453310X12647083620967.
Disease-stabilizing therapy with the histone deacetylase inhibitor valproic acid and all-trans retinoic acid (ATRA) has been investigated in acute myelogenous leukemia (AML) in a number of trials. Experimental studies suggest that valproic acid induces a broad chemoresistant phenotype in human AML cells; however, clinical observations combining valproic acid with conventional therapy in a disease-stabilizing setting have not been reported that would confirm this as a clinical issue. We describe five patients receiving oral treatment with low-dose oral 6-mercaptopurin and/or hydroxyurea together with ATRA+valproric acid+theophylline. Hyperleukocytosis was controlled by low doses of the cytotoxic drugs, no unexpected toxicity appeared and the increases in normal peripheral blood cell counts induced by ATRA+valproic acid+theophylline were maintained during therapy. In two patients increasing blast counts later occurred during chemotherapy; a change to the alternative cytotoxic drug was then effective in controlling hyperleukocytosis. We conclude that valproic acid+ATRA+theophylline combined with 6-mercaptopurin or hydroxyurea can be safe and effective in palliative treatment of human AML.
在多项试验中，已对组蛋白去乙酰化酶抑制剂丙戊酸和全反式维甲酸（ATRA）用于急性髓性白血病（AML）的疾病稳定治疗进行了研究。实验研究表明，丙戊酸可在人AML细胞中诱导广泛的化学抗性表型；然而，尚未有关于在疾病稳定环境中将丙戊酸与传统疗法联合应用的临床观察报告来证实这是一个临床问题。我们描述了5例接受低剂量口服6-巯基嘌呤和/或羟基脲与ATRA +丙戊酸+茶碱联合口服治疗的患者。高白细胞血症通过低剂量的细胞毒性药物得到控制，未出现意外毒性，并且在治疗期间由ATRA +丙戊酸+茶碱诱导的正常外周血细胞计数增加得以维持。在两名患者中，化疗后期出现了原始细胞计数增加；随后改用替代细胞毒性药物有效地控制了高白细胞血症。我们得出结论，丙戊酸+ ATRA +茶碱联合6-巯基嘌呤或羟基脲在人类AML的姑息治疗中可能是安全有效的。
