Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913.
Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913.
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DOI：
10.3324/haematol.2020.247973
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发表时间：
2021-06-01
期刊：
影响因子：
10.1
通讯作者：
Foà R
中科院分区：
文献类型：
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作者：
Chiaretti S;Messina M;Della Starza I;Piciocchi A;Cafforio L;Cavalli M;Taherinasab A;Ansuinelli M;Elia L;Albertini Petroni G;La Starza R;Canichella M;Lauretti A;Puzzolo MC;Pierini V;Santoro A;Spinelli O;Apicella V;Capria S;Di Raimondo F;De Fabritiis P;Papayannidis C;Candoni A;Cairoli R;Cerrano M;Fracchiolla N;Mattei D;Cattaneo C;Vitale A;Crea E;Fazi P;Mecucci C;Rambaldi A;Guarini A;Bassan R;Foà R
费城样（Ph样）急性淋巴细胞白血病（ALL）病例的早期识别可能会影响该B系ALL亚群的管理和结局。为了评估Ph样状态在儿科启发、微小残留病（MRD）驱动的试验中的预后价值，我们筛选了88例主要融合基因（BCR-ABL 1、ETV 6-RUNX 1、TCF 3-PBX 1和KTM 2Ar）阴性的B系ALL病例，这些病例入组了GIMEMA LAL 1913成人BCR/ABL 1阴性ALL一线方案。使用“BCR/ABL 1样预测因子”进行的筛查确定了28例Ph样病例（31.8%），其特征为CRLF 2过表达（35.7%）、JAK/STAT通路突变（33.3%）、IKZF 1（63.6%）、BTG 1（50%）和EBF 1（27.3%）缺失以及靶向酪氨酸激酶或CRLF 2的重排（40%）。与结果的相关性强调：i）与非Ph样病例相比，Ph样病例的完全缓解率显著降低（74.1% vs. 91.5%，P=0.044）; ii）在时间点2，决定移植分配时，52.9%的Ph样病例与20%的非Ph样病例为MRD阳性（P=0.025）; iii）Ph样特征是与时间点2时MRD阳性风险较高相关的唯一参数（P=0.014）; iv）在24个月时，与非Ph样患者相比，Ph样患者的无事件和无疾病生存率显著较低（分别为33.5%和66.2%，P=0.005和45.5%和72.3%，P=0.062）。本研究记录了Ph样患者的完全缓解率、无事件生存期和无疾病生存期较低，以及在面向儿科和MRD驱动的成人ALL方案中MRD持续性较高，因此加强了诊断时Ph样ALL患者的早期识别对于完善风险分层和优化治疗策略至关重要。临床试验政府标识符：02067143。
Early recognition of Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) cases could impact on the management and outcome of this subset of B-lineage ALL. In order to assess the prognostic value of the Ph-like status in a pediatric-inspired, minimal residual disease (MRD)- driven trial, we screened 88 B-lineage ALL cases negative for major fusion genes (BCR-ABL1, ETV6-RUNX1, TCF3-PBX1 and KTM2Ar) enrolled in the GIMEMA LAL1913 front-line protocol for adult BCR/ABL1-negative ALL. The screening - performed using the “BCR/ABL1-like predictor” - identified 28 Ph-like cases (31.8%), characterized by CRLF2 overexpression (35.7%), JAK/STAT pathway mutations (33.3%), IKZF1 (63.6%), BTG1 (50%) and EBF1 (27.3%) deletions, and rearrangements targeting tyrosine kinases or CRLF2 (40%). The correlation with outcome highlighted that: i) the complete remission rate was significantly lower in Ph-like compared to non-Phlike cases (74.1% vs. 91.5%, P=0.044); ii) at time point 2, decisional for transplant allocation, 52.9% of Ph-like cases versus 20% of non-Ph-like were MRD-positive (P=0.025); iii) the Ph-like profile was the only parameter associated with a higher risk of being MRD-positive at time point 2 (P=0.014); iv) at 24 months, Ph-like patients had a significantly inferior event-free and disease-free survival compared to non-Ph-like patients (33.5% vs. 66.2%, P=0.005 and 45.5% vs. 72.3%, P=0.062, respectively). This study documents that Ph-like patients have a lower complete remission rate, event-free survival and disease-free survival, as well as a greater MRD persistence also in a pediatric-oriented and MRD-driven adult ALL protocol, thus reinforcing that the early recognition of Ph-like ALL patients at diagnosis is crucial to refine risk-stratification and to optimize therapeutic strategies. Clinicaltrials gov. Identifier: 02067143.