A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial
A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial
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DOI：
10.1182/blood.2019004741
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发表时间：
2020-10-15
期刊：
影响因子：
20.3
通讯作者：
Koh, Katsuyoshi
中科院分区：
文献类型：
--
作者：
Tomizawa, Daisuke;Miyamura, Takako;Koh, Katsuyoshi
婴儿急性淋巴细胞白血病（ALL），特别是KMT 2A基因重排（KMT 2A-r）的预后是令人沮丧的。日本一直在努力研究造血干细胞移植（HSCT）对KMT 2A-r ALL婴儿的作用，但结果改善不大。在日本儿童白血病/淋巴瘤研究组MLL-10试验中，根据KMT 2A状态、年龄和中枢神经系统白血病的存在，将ALL婴儿分为3个风险组（低风险[LR]、中等风险[IR]和高风险[HR]）。儿童肿瘤组AALL 0631改良化疗，在早期强化中添加高剂量阿糖胞苷，被引入KMT 2A-r患者，HSCT的选择仅限于HR患者。还评估了微小残留病（MRD）的作用。将90名合格婴儿分为LR（n=15）、IR（n=19）或HR（n=56）风险组。KMT 2A-r ALL（IR + HR）患者的3年无事件生存率（EFS）为66.2%（标准误[SE]，5.6%），而KMT 2A（KMT 2A-g）ALL（LR）患者的3年EFS率为93.3%（SE，6.4%）。IR患者的3年EFS率为94.4%（SE，5.4%），HR患者为56.6%（SE，6.8%）。多因素分析中，女性和早期巩固治疗结束时MRD ≥ 0.01%是预后不良的重要因素。本研究中的风险分层和强化化疗的引入是有效的，并且能够消除KMT 2A-r ALL婴儿亚组的HSCT。早期清除MRD似乎已转化为有利的结局，应纳入未来试验的风险分层中。
The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children's Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n=15), IR (n=19), or HR (n=56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD >= 0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials.