RESULTS OF MEDICAL-RESEARCH-COUNCIL CHILDHOOD LEUKEMIA TRIAL UKALL-VIII (REPORT TO THE MEDICAL-RESEARCH-COUNCIL ON BEHALF OF THE WORKING PARTY ON LEUKEMIA IN CHILDHOOD)
RESULTS OF MEDICAL-RESEARCH-COUNCIL CHILDHOOD LEUKEMIA TRIAL UKALL-VIII (REPORT TO THE MEDICAL-RESEARCH-COUNCIL ON BEHALF OF THE WORKING PARTY ON LEUKEMIA IN CHILDHOOD)
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DOI：
10.1111/j.1365-2141.1991.tb04415.x
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发表时间：
1991-06-01
影响因子：
6.5
通讯作者：
PETO, J
中科院分区：
文献类型：
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作者：
EDEN, OB;LILLEYMAN, JS;PETO, J
在20世纪70年代，尽管表面上类似的治疗，淋巴细胞性白血病(ALL)儿童的预后在一些国家，特别是美国和西德，比其他国家改善得更多。为了找出原因，英国(UK)医学研究理事会(MRC)第一阶段进行了儿童ALL试验。UKALL VIII的设计目的是看看是否可以在英国使用相同的方案(CCG 162)获得类似于美国儿童癌症研究小组(CCSG)的结果。162方案是美国儿童癌症研究小组在20世纪70年代设计的一系列方案之一，专门用于他们的平均风险患者(除3-6岁的白细胞低于10×10(9)/L的儿童外，所有ALL初始白细胞计数高于50×10(9)/L的儿童)。他们研究的一个ARM(1A)被MRC应用于英国所有确诊为ALL的0-14岁儿童。829名连续患者进入1980至1984年间。最初的199名患者按照最初的方案162(ARM 1A)组成单组研究，但随后的630名儿童在诱导的第一个2d被随机接受或不接受两剂柔红霉素治疗。这一随机化尝试回答了一个重要的问题，即是否使用四种诱导剂而不是三种诱导剂影响了无事件生存率。与CCSG在他们的方案中所做的一样，在这个阶段也引入了第二个在2到3年间继续治疗的随机分组。在至少5年的随访期内，整个组的无瘤存活率为55%，与之前所有的UKALL试验相比，这是一个相当大的进步。结果直接与CCSG162(“平均风险”患者)和他们的美国同行相比较的患者的结果相似。柔红霉素与更多的早期死亡相关，但对于那些获得缓解的患者来说，提高了无病生存率。两年后停止治疗的儿童比继续治疗三年的儿童复发更多，但这被第三年治疗死亡率的增加所平衡。UKALL VIII的结果与CCSG的结果相似，这表明以前的MRC方案没有足够的持续性和强度，特别是在治疗的维持阶段。柔红霉素可能提供了更好的疾病控制，尽管毒性增加，3年的维持治疗在长期存活方面没有任何优势，尽管它可能降低了早期复发率。
During the 1970s, despite apparently similar treatment, the prognosis for children with lymphoblastic leukaemia (ALL) improved more in some countries, notably the United States and West Germany, than in others. To find out why, the first phase of the United Kingdom (UK) Medical Research Council (MRC) childhood ALL trial. UKALL VIII, was designed to see whether similar results to the United States Children's Cancer Study Group (CCSG) could be obtained in the U.K. using an identical protocol (CCG 162). Protocol 162 was one of a series of regimens devised by the American Children's Cancer Study Group in the 1970s and was used specifically for their average risk patients (all children with ALL with an initial white cell count up to 50 x 10(9)/l except those aged 3-6 years with white cell counts under 10 x 10(9)/l). One arm (1A) of their study was adopted by the MRC for all children in the U.K. aged 0-14 years with confirmed ALL.Eight hundred and twenty-nine consecutive patients were entered between 1980 and 1984. The first 199 patients formed a single arm study as per the original protocol 162 (arm 1A), but the subsequent 630 children were randomized to receive or not two doses of daunorubicin on the first 2 d of induction. This randomization was an attempt to answer the important question as to whether event-free survival was influenced by the use of four rather than three induction agents. A second randomization between 2 and 3 years continuing therapy was also introduced at this stage as it had been by the CCSG in their protocol. With a minimum follow up period of more than 5 years, disease-free survival for the whole group is 55%, a considerable improvement on all previous UKALL trials. Results for patients directly comparable with those in CCSG 162 ('average risk' patients) and their American counterparts were similar.Daunorubicin was associated with more early deaths but improved disease-free survival for those achieving remission. More children relapsed who stopped treatment after 2 years than those who continued for 3, but this was balanced by increased treatment mortality in the third year.The fact that for UKALL VIII the results were similar to those of the CCSG suggests that previous MRC protocols were not sufficiently sustained and intensive, particularly during the maintenance phase of treatment. Daunorubicin may have provided better disease control, albeit with increased toxicity, and 3 years of maintenance therapy did not confer any advantage in long-term survival over 2 even though it may have reduced the rate of early relapse.