Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232
Prognostic significance of minimal residual disease in high risk B-ALL: a report from Children's Oncology Group study AALL0232
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DOI：
10.1182/blood-2015-03-633685
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发表时间：
2015-08-20
期刊：
影响因子：
20.3
通讯作者：
Larsen, Eric
中科院分区：
文献类型：
--
作者：
Borowitz, Michael J.;Wood, Brent L.;Larsen, Eric
微量残留病（MRD）在儿童b前体急性淋巴细胞白血病（B-ALL）中具有很高的预后。在儿童肿瘤组高风险B-ALL研究AALL0232中，我们调查了随机分为2 × 2因子设计的受试者的MRD，这些受试者在中期维持（IM）期间接受高剂量甲氨蝶呤（HD-MTX）或卡皮兹甲氨蝶呤（C-MTX），或在诱导期间接受强的松或地塞米松。末诱导MRD >= 0.1%或早期形态学反应缓慢的受试者非随机分配接受第二次IM和延迟强化期。MRD在2个参考实验室中的1个用6色流式细胞仪测量，两者之间具有良好的一致性。终末诱导MRD = 0.01%。虽然HD-MTX优于C-MTX，但MRD在两组中仍具有预后意义（MRD阴性和C-MTX阳性受试者中为86% +/- 2% vs 58% +/- 4%； HD-MTX受试者中为88% +/- 2% vs 68% +/- 4%）。对MRD为0.1%的患者进行强化治疗并没有改善5年EFS或总生存期（OS）。然而，这些患者的早期复发率与MRD阴性患者相似，0.1%至1% MRD患者的EFS/OS曲线在3年和4年时与0.01%至0.1% MRD患者的曲线交叉，这表明强化治疗改变了MRD阳性患者的病程。针对mrd阳性组的额外干预可能会进一步改善结果。
Minimal residual disease (MRD) is highly prognostic in pediatric B-precursor acute lymphoblastic leukemia (B-ALL). In Children's Oncology Group high-risk B-ALL study AALL0232, we investigated MRD in subjects randomized in a 2 x 2 factorial design to receive either high-dose methotrexate (HD-MTX) or Capizzi methotrexate (C-MTX) during interim maintenance (IM) or prednisone or dexamethasone during induction. Subjects with end-induction MRD >= 0.1% or those with morphologic slow early response were nonrandomly assigned to receive a second IM and delayed intensification phase. MRD was measured by 6-color flow cytometry in 1 of 2 reference labs, with excellent agreement between the two. Subjects with end-induction MRD = 0.01%. Although HD-MTX was superior to C-MTX, MRD retained prognostic significance in both groups (86% +/- 2% vs 58% +/- 4% for MRD-negative vs positive C-MTX subjects; 88% +/- 2% vs 68% +/- 4% for HD-MTX subjects). Intensified therapy given to subjects with MRD > 0.1% did not improve either 5-year EFS or overall survival (OS). However, these subjects showed an early relapse rate similar to that seen in MRD-negative ones, with EFS/OS curves for patients with 0.1% to 1% MRD crossing those with 0.01% to 0.1% MRD at 3 and 4 years, thus suggesting that the intensified therapy altered the disease course of MRD-positive subjects. Additional interventions targeted at the MRD-positive group may further improve outcome.