Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group
Prognostic impact of t(16;21)(p11;q22) and t(16;21)(q24;q22) in pediatric AML: a retrospective study by the I-BFM Study Group
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DOI：
10.1182/blood-2018-05-849059
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发表时间：
2018-10-11
期刊：
影响因子：
20.3
通讯作者：
Zwaan, C. Michel
中科院分区：
文献类型：
--
作者：
Noort, Sanne;Zimmermann, Martin;Zwaan, C. Michel
为了研究急性髓系白血病（AML）中罕见遗传畸变（如t（16：21））的预后相关性，需要国际合作。可以区分两种不同类型的t（16：21）易位：t（16：21）（p11;q22），导致FUS-ERG融合基因; t（16：21）（q24;q22），导致RUNX 1-核心结合因子（CBFA 2 T3）。我们收集了来自14个国际合作研究组的54例t（16：21）重排的儿童AML病例的临床和生物学特征数据，这些研究组参加了国际柏林-法兰克福-米因斯特（I-BFM）AML研究组。1997年至2013年诊断的AML-BFM队列用作参考队列。与参考队列相比，RUNX 1-CBFA 2 T3（n = 23）的中位白色血细胞计数（12.5 x 10（9）/L，P = .03）显著降低。FUS-ERG重排的AML（n = 31）没有主要的法国-美国-英国（FAB）类型，而76%的RUNX 1-CBFA 2 T3具有M1/M2 FAB类型（M1，M2），与参考队列有显著差异（P = .004）。FUS-ERG患者的4年无事件生存率（EFS）为7%（标准误[SE] = 5%），显著低于参考队列（51%，SE = 1%，P <0.001）。RUNX 1-CBFA 2 T3的4年EFS为77%（SE = 8%，P = 0.06），显著高于参考队列。FUS-ERG的累积复发率为74%（SE = 8%），RUNX 1-CBFA 2 T3为0%（SE = 0%），而参考队列为32%（SE = 1%）（P <0.001）。多变量分析将FUS-ERG和RUNX 1-CBFA 2 T3确定为独立风险因素，风险比分别为1.9（P < .0001）和0.3（P = .025）。这些结果描述了2种临床相关的不同儿科AML亚型。与其他核心结合因子AML相似，RUNX 1-CBFA 2 T3重排AML患者可能受益于标准风险治疗的分层，而FUS-ERG重排AML患者应视为高风险。
To study the prognostic relevance of rare genetic aberrations in acute myeloid leukemia (AML), such as t(16:21), international collaboration is required. Two different types of t(16:21) translocations can be distinguished: t(16:21)(p11;q22), resulting in the FUS-ERG fusion gene; and t(16:21)(q24;q22), resulting in RUNX1-core binding factor (CBFA2T3). We collected data on clinical and biological characteristics of 54 pediatric AML cases with t(16:21) rearrangements from 14 international collaborative study groups participating in the international Berlin-Frankfurt-Miinster (I-BFM) AML study group. The AML-BFM cohort diagnosed between 1997 and 2013 was used as a reference cohort. RUNX1-CBFA2T3 (n = 23) had significantly lower median white blood cell count (12.5 x 10(9)/L, P = .03) compared with the reference cohort. FUS-ERG rearranged AML (n = 31) had no predominant French-American-British (FAB) type, whereas 76% of RUNX1-CBFA2T3 had an M1/M2 FAB type (M1, M2), significantly different from the reference cohort (P = .004). Four-year event-free survival (EFS) of patients with FUS-ERG was 7% (standard error [SE] = 5%), significantly lower compared with the reference cohort (51%, SE = 1%, P < .001). Four-year EFS of RUNX1-CBFA2T3 was 77% (SE = 8%, P = .06), significantly higher compared with the reference cohort. Cumulative incidence of relapse was 74% (SE = 8%) in FUS-ERG, 0% (SE = 0%) in RUNX1-CBFA2T3, compared with 32% (SE = 1%) in the reference cohort (P < .001). Multivariate analysis identified both FUS-ERG and RUNX1-CBFA2T3 as independent risk factors with hazard ratios of 1.9 (P < .0001) and 0.3 (P = .025), respectively. These results describe 2 clinically relevant distinct subtypes of pediatric AML. Similarly to other core-binding factor AMLs, patients with RUNX1-CBFA2T3 rearranged AML may benefit from stratification in the standard risk treatment, whereas patients with FUS-ERG rearranged AML should be considered high-risk.