Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, Rees J, Hann I, Stevens R, Burnett A, Goldstone A
Departments of Haematology, University College London; the Royal Free and Great Ormond St Children's Hospitals, London, UK.
Blood. 1998 Oct 1;92(7):2322-33.
Cytogenetics is considered one of the most valuable prognostic determinants in acute myeloid leukemia (AML). However, many studies on which this assertion is based were limited by relatively small sample sizes or varying treatment approach, leading to conflicting data regarding the prognostic implications of specific cytogenetic abnormalities. The Medical Research Council (MRC) AML 10 trial, which included children and adults up to 55 years of age, not only affords the opportunity to determine the independent prognostic significance of pretreatment cytogenetics in the context of large patient groups receiving comparable therapy, but also to address their impact on the outcome of subsequent transplantation procedures performed in first complete remission (CR). On the basis of response to induction treatment, relapse risk, and overall survival, three prognostic groups could be defined by cytogenetic abnormalities detected at presentation in comparison with the outcome of patients with normal karyotype. AML associated with t(8;21), t(15;17) or inv(16) predicted a relatively favorable outcome. Whereas in patients lacking these favorable changes, the presence of a complex karyotype, -5, del(5q), -7, or abnormalities of 3q defined a group with relatively poor prognosis. The remaining group of patients including those with 11q23 abnormalities, +8, +21, +22, del(9q), del(7q) or other miscellaneous structural or numerical defects not encompassed by the favorable or adverse risk groups were found to have an intermediate prognosis. The presence of additional cytogenetic abnormalities did not modify the outcome of patients with favorable cytogenetics. Subgroup analysis demonstrated that the three cytogenetically defined prognostic groups retained their predictive value in the context of secondary as well as de novo AML, within the pediatric age group and furthermore were found to be a key determinant of outcome from autologous or allogeneic bone marrow transplantation (BMT) in first CR. This study highlights the importance of diagnostic cytogenetics as an independent prognostic factor in AML, providing the framework for a stratified treatment approach of this disease, which has been adopted in the current MRC AML 12 trial.
细胞遗传学被认为是急性髓系白血病（AML）中最有价值的预后决定因素之一。然而，许多基于这一论断的研究受到样本量相对较小或治疗方法各异的限制，导致关于特定细胞遗传学异常的预后意义的数据相互矛盾。医学研究委员会（MRC）的AML 10试验纳入了儿童及55岁以下的成年人，这不仅为在接受可比治疗的大型患者群体中确定预处理细胞遗传学的独立预后意义提供了机会，还能探讨其对首次完全缓解（CR）后进行的后续移植程序结果的影响。根据诱导治疗反应、复发风险和总生存期，与核型正常患者的结果相比，可通过初诊时检测到的细胞遗传学异常定义三个预后组。与t(8;21)、t(15;17)或inv(16)相关的AML预后相对较好。而在缺乏这些有利变化的患者中，复杂核型、-5、del(5q)、-7或3q异常定义了一个预后相对较差的组。其余患者组，包括那些有11q23异常、+8、+21、+22、del(9q)、del(7q)或其他未被有利或不利风险组涵盖的杂项结构或数字缺陷的患者，预后中等。额外细胞遗传学异常的存在并未改变具有有利细胞遗传学患者的结果。亚组分析表明，这三个由细胞遗传学定义的预后组在继发性和原发性AML中、在儿童年龄组中均保留了其预测价值，并且还被发现是首次CR时自体或异基因骨髓移植（BMT）结果的关键决定因素。这项研究强调了诊断细胞遗传学作为AML独立预后因素的重要性，为这种疾病的分层治疗方法提供了框架，目前的MRC AML 12试验已采用该方法。
