Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status:: results of the Japan Infant Leukaemia Study (MLL96)
Risk-directed treatment of infant acute lymphoblastic leukaemia based on early assessment of MLL gene status:: results of the Japan Infant Leukaemia Study (MLL96)
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DOI：
10.1046/j.1365-2141.2002.03754.x
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发表时间：
2002-09-01
影响因子：
6.5
通讯作者：
Ishii, E
中科院分区：
文献类型：
--
作者：
Isoyama, K;Eguchi, M;Ishii, E
我们研究了13个月以下急性淋巴细胞白血病（ALL）婴儿风险导向治疗的有效性。55名婴儿被分配到不同的治疗方案（1995年12月至1998年12月）的基础上，他们的MLL基因状态在诊断。42例（76.3%）有MLL基因重排（MLL（+）），并接受缓解诱导治疗，随后接受序贯强化化疗，包括多种遗传毒性药物（MLL 9601方案）。如果有合适的供体，则尝试造血干细胞移植（HSCT）。13名婴儿（23.7%）被归类为MLL（-），并接受了2.5年的高危B-ALL强化化疗（MLL 9602方案）。42例MLL（+）ALL患儿中38例（90.5%）完全缓解，13例MLL（-）患儿完全缓解。在MLL（+）亚组中，诊断后3年的估计无事件生存率（EFS）为34.0% ± 7.5%，而MLL（-）亚组为92.3% ± 7.4%（总体比较，对数秩分析P = 0.001）。诊断时年龄小于6个月（风险比= 6.87，95%CI = 0.91-52.3; P = 0.013）和中枢神经系统（CNS）受累（风险比= 2.92，95%CI = 1.29-6.63; P = 0.015）均为较差结局的显著独立预测因素。这些发现表明在临床病程早期将婴儿ALL分类为MLL（+）或MLL（-）并相应选择治疗具有战略优势。高危B系ALL的标准化疗似乎足以治疗MLL（-）病例。对于患有MLL（+）疾病的婴儿，特别是那些最初累及CNS白血病或年龄小于6个月或两者兼而有之的婴儿，需要采取新的治疗措施。
We studied the effectiveness of risk-directed therapy for infants younger than 13 months of age with acute lymphoblastic leukaemia (ALL). Fifty-five infants were assigned to different treatment programs (from December 1995 to December 1998) on the basis of their MLL gene status at diagnosis. Forty-two cases (76.3%) had a rearranged MLL gene (MLL (+) ) and were treated with remission induction therapy followed by sequential intensive chemotherapy, including multiple genotoxic agents (MLL9601 protocol). Haematopoietic stem cell transplantation (HSCT) was attempted if suitable donors were available. Thirteen infants (23.7%) were classified as MLL (-) and treated for 2.5 years with intensive chemotherapy for high-risk B-ALL (MLL9602 protocol). Complete remission was induced in 38 of the 42 infants (90.5%) with MLL (+) ALL and in all 13 patients (100%) with MLL (-) disease. In the MLL (+) subgroup, the estimated event-free survival (EFS) rate at 3 years post diagnosis was 34.0% +/- 7.5%, compared with 92.3% +/- 7.4% in the MLL (-) subgroup (overall comparison, P = 0.001 by log-rank analysis). Both age less than 6 months (hazard ratio = 6.87, 95% CI = 0.91-52.3; P = 0.013) and central nervous system (CNS) involvement at diagnosis (hazard ratio = 2.92 95% CI = 1.29-6.63; P = 0.015) were significant independent predictors of an inferior outcome. These findings indicate a strategic advantage in classifying infant ALL as either MLL (+) or MLL (-) early in the clinical course and selecting therapy accordingly. Standard chemotherapy for high-risk B-lineage ALL appeared adequate for MLL (-) cases. Novel therapeutic initiatives are warranted for infants with MLL (+) disease, particularly those with initial CNS leukaemic involvement or age less than 6 months, or both.