期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2004
卷号:101
期号:15
页码:5328-5335
DOI:10.1073/pnas.0400053101
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Both all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As2O3, and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR{alpha} (promyelocytic leukemia-retinoic acid receptor {alpha}) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high ([≥]90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RAR{alpha} transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As2O3 mono-therapy (P < 0.01). This difference persisted after consolidation (P < 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed (P < 0.05) after a follow-up of 8-30 months (median: 18 months). Synergism of ATRA and As2O3 on apoptosis and degradation of PML-RAR{alpha} oncoprotein might provide a plausible explanation for superior efficacy of combinative therapy in clinic. In conclusion, the ATRA/As2O3 combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.