Anthony V. Moorman, Hazel Robinson, Claire Schwab, and Christine J. Harrison, Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle; Sue M. Richards, University of Oxford; Christopher D. Mitchell, John Radcliffe Hospital, Oxford; Jeremy Hancock, Bristol Genetics Laboratory, North Bristol National Health Service Trust, Bristol; Nicholas Goulden, Great Ormond Street Hospital, London; and Ajay Vora, Sheffield Children's Hospital, Sheffield, United Kingdom.
J Clin Oncol. 2013 Sep 20;31(27):3389-96. doi: 10.1200/JCO.2013.48.9377. Epub 2013 Aug 12.
To evaluate the effect on outcome of intensifying therapy for patients with acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21).
We report two cohorts of patients treated on Medical Research Council ALL97 or United Kingdom (UK) ALL2003. iAMP21 was identified retrospectively in ALL97 and was not used to guide therapy. However, in UKALL2003, iAMP21 was determined prospectively, and patients were allocated to the most intensive treatment arm (regimen C), which included augmented Berlin-Frankfurt-Munster consolidation, escalating Capizzi maintenance, double delayed intensification, and an option for first remission transplantation. The presence of iAMP21 was determined by fluorescence in situ hybridization using probes specific for the RUNX1 gene.
iAMP21 was identified in 2% of patients with B-cell precursor ALL treated on UKALL2003 and ALL97. The event-free survival, relapse, and overall survival rates at 5 years for iAMP21 patients treated on ALL97 and UKALL2003 were 29% and 78%, 70% and 16%, and 67% and 89%, respectively (all P < .01). Patients treated on ALL97 had an increased risk of relapse compared with patients treated on UKALL2003 (hazard ratio, 7.2; 95% CI, 2.91 to 17.87; P < .001).
iAMP21 patients with ALL benefitted from receiving more intensive therapy in UKALL2003. In UKALL2011, they will continue to be treated as cytogenetic high risk, receive intensive chemotherapy (regimen C), and will only be recommended for transplantation if they do not achieve a complete remission by the end of induction therapy. This study illustrates how the discovery and characterization of disease-specific genetic aberrations can be used to tailor therapy more precisely.
评估强化治疗对伴有 21 号染色体内部扩增（iAMP21）的急性淋巴细胞白血病（ALL）患者结局的影响。
我们报告了在医学研究理事会 ALL97 或英国 ALL2003 中接受治疗的两批患者。在 ALL97 中，iAMP21 是回顾性识别的，并未用于指导治疗。然而，在 UKALL2003 中，iAMP21 是前瞻性确定的，并且患者被分配到最强化的治疗组（方案 C），其中包括强化柏林-法兰克福-慕尼黑巩固治疗、逐步增加的 Capizzi 维持治疗、双重延迟强化治疗，以及第一次缓解移植的选择。使用针对 RUNX1 基因的特异性荧光原位杂交探针来确定 iAMP21 的存在。
在接受 UKALL2003 和 ALL97 治疗的 B 细胞前体 ALL 患者中，有 2%的患者存在 iAMP21。在 ALL97 和 UKALL2003 中接受治疗的 iAMP21 患者的无事件生存、复发和总生存率分别为 29%和 78%、70%和 16%、67%和 89%（均 P <.01）。与接受 UKALL2003 治疗的患者相比，接受 ALL97 治疗的患者复发风险增加（危险比，7.2；95%置信区间，2.91 至 17.87；P <.001）。
在 UKALL2003 中，患有 iAMP21 的 ALL 患者从接受更强化的治疗中获益。在 UKALL2011 中，他们将继续被视为细胞遗传学高危，接受强化化疗（方案 C），并且只有在诱导治疗结束时未达到完全缓解的情况下，才会被推荐进行移植。本研究说明了如何利用疾病特异性遗传异常的发现和特征来更精确地定制治疗。
