Treatment of High-Risk Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in Adolescents and Adults According to Early Cytologic Response and Minimal Residual Disease After Consolidation Assessed by Flow Cytometry: Final Results of the PETHEMA ALL-AR-03 Trial
Treatment of High-Risk Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia in Adolescents and Adults According to Early Cytologic Response and Minimal Residual Disease After Consolidation Assessed by Flow Cytometry: Final Results of the PETHEMA ALL-AR-03 Trial
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DOI：
10.1200/jco.2013.52.2425
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发表时间：
2014-05-20
影响因子：
45.3
通讯作者：
Feliu, Evarist
中科院分区：
文献类型：
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作者：
Ribera, Josep-Maria;Oriol, Albert;Feliu, Evarist
目的微小残留病(MRD)是成人急性淋巴细胞白血病(ALL)的一个重要预后因素，可用于治疗决策。西班牙血液病方案(PETHEMA)ALL-AR-03试验(治疗高危成人急性淋巴细胞性白血病[LAL-AR/2003])根据早期细胞学反应(第14天)和巩固后Flow-MRD水平，将无费城(Ph)染色体的高危ALL(HR-ALL)的青少年和成人患者(年龄15-60岁)分配给化疗或异基因造血干细胞移植(allo-HSCT)。326例患者中282例(87%)获完全缓解，236例完成早期巩固的患者中179例(76%)按意向分配接受allo-HSCT或化疗(108例)。五年无病生存率(DFS)和总生存率(OS)在整个系列中分别为37%和35%，接受allo-HSCT的患者分别为32%和37%，接受化疗的患者分别为55%和59%。多变量分析显示诱导后MRD清除率差(>；=1×10(-3)，早期巩固后>；=5×10(-4))是DFS和OS的唯一预后因素。结论在避免异基因造血干细胞移植的情况下，Ph阴性HR-ALL的青少年和成人早期反应良好，巩固后低Flow-MRD水平是非常有利的预后因素。在这项研究中，MRD清除模式是DFS和OS的唯一预后因素。(C)美国临床肿瘤学会2014年
PurposeMinimal residual disease (MRD) is an important prognostic factor in adults with acute lymphoblastic leukemia (ALL) and may be used for treatment decisions. The Programa Espanol de Tratamientos en Hematologia (PETHEMA) ALL-AR-03 trial (Treatment of High Risk Adult Acute Lymphoblastic Leukemia [LAL-AR/2003]) assigned adolescent and adult patients (age 15 to 60 years) with high-risk ALL (HR-ALL) without the Philadelphia (Ph) chromosome to chemotherapy or to allogeneic hematopoietic stem-cell transplantation (allo-HSCT) according to early cytologic response (day 14) and flow-MRD level after consolidation.Patients and MethodsPatients with good early cytologic response (< 10% blasts in bone marrow at day 14 of induction) and a flow-MRD level less than 5 x 10(-4) at the end of consolidation were assigned to delayed consolidation and maintenance therapy, and allo-HSCT was scheduled in patients with poor early cytologic response or flow-MRD level >= 5 x 10(-4).ResultsComplete remission was attained in 282 (87%) of 326 patients, and 179 (76%) of 236 patients who completed early consolidation were assigned by intention-to treat to receive allo-HSCT (71) or chemotherapy (108). Five-year disease-free survival (DFS) and overall survival (OS) probabilities were 37% and 35% for the whole series, 32% and 37% for patients assigned to allo-HSCT, and 55% and 59% for those assigned to chemotherapy. Multivariable analysis showed poor MRD clearance (>= 1 x 10(-3) after induction and >= 5 x 10(-4) after early consolidation) as the only prognostic factor for DFS and OS.ConclusionPrognosis for Ph-negative HR-ALL in adolescents and adults with good early response to induction and low flow-MRD levels after consolidation is quite favorable when allo-HSCT is avoided. In this study, the pattern of MRD clearance was the only prognostic factor for DFS and OS. (C) 2014 by American Society of Clinical Oncology