Takachi Takayuki, Watanabe Tomoyuki, Miyamura Takako, Moriya Saito Akiko, Deguchi Takao, Hori Toshinori, Yamada Tomomi, Ohmori Shigeru, Haba Masami, Aoki Yuki, Ishimaru Sae, Sasaki Shinya, Ohshima Junjiro, Iguchi Akihiro, Takahashi Yoshiyuki, Hyakuna Nobuyuki, Manabe Atsushi, Horibe Keizo, Ishii Eiichi, Koh Katsuyoshi, Tomizawa Daisuke
Department of Hematology and Oncology, Shizuoka Children's Hospital, Shizuoka, Japan.
Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, Nisshin, Japan.
Blood Adv. 2021 Oct 12;5(19):3891-3899. doi: 10.1182/bloodadvances.2020004157.
The role of allogeneic hematopoietic stem cell transplantation (HSCT) for infants with acute lymphoblastic leukemia (ALL) and KMT2A gene rearrangement (KMT2A-r) is controversial in terms of both its efficacy and potential for acute and late toxicities. In Japanese Pediatric Leukemia/Lymphoma Study Group trial MLL-10, by introducing intensive chemotherapy, indication of HSCT was restricted to patients with high-risk (HR) features only (KMT2A-r and either age <180 days or presence of central nervous system leukemia). Of the 56 HR patients, 49 achieved complete remission. Forty-three patients received HSCT in first remission including 38 patients receiving protocol-specified HSCT with conditioning consisting of individualized targeted doses of busulfan, etoposide, and cyclophosphamide. Three-year event-free survival (EFS) of 56.8% (95% confidence interval [CI], 42.4% to 68.8%) and overall survival of 80.2% (95% CI, 67.1% to 88.5%) were accomplished. Univariable analysis showed that Interfant-HR criteria and flow cytometric minimal residual disease (MRD; ≥0.01%), both at the end of induction and at the end of consolidation (EOC), were significantly associated with poorer EFS. In the multivariable analysis, positive MRD at EOC was solely associated with poor EFS (P < .001). Rapid pretransplant MRD clearance and tailored HSCT strategy in the MLL-10 trial resulted in a favorable outcome for infants with HR KMT2A-r ALL. However, considering the high rate of potentially life-threatening toxicities and the risk of late effects, its indication should be further restricted or even eliminated in the future by introducing more effective therapeutic modalities with minimal toxicities. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.
对于患有急性淋巴细胞白血病（ALL）且伴有KMT2A基因重排（KMT2A-r）的婴儿，异基因造血干细胞移植（HSCT）在疗效以及急慢性毒性发生可能性方面存在争议。在日本儿童白血病/淋巴瘤研究组的MLL-10试验中，通过引入强化化疗，HSCT的适应症仅限于具有高危（HR）特征的患者（KMT2A-r且年龄<180天或存在中枢神经系统白血病）。在56例HR患者中，49例实现完全缓解。43例患者在首次缓解期接受了HSCT，其中38例接受了方案规定的HSCT，预处理方案包括个体化靶向剂量的白消安、依托泊苷和环磷酰胺。实现了3年无事件生存率（EFS）为56.8%（95%置信区间[CI]，42.4%至68.8%），总生存率为80.2%（95%CI，67.1%至88.5%）。单变量分析显示，诱导期末和巩固期末（EOC）的Interfant-HR标准以及流式细胞术检测的微小残留病（MRD；≥0.01%）与较差的EFS显著相关。在多变量分析中，EOC时MRD阳性仅与较差的EFS相关（P<.001）。MLL-10试验中快速的移植前MRD清除和定制的HSCT策略为患有HR KMT2A-r ALL的婴儿带来了良好的结果。然而，考虑到潜在的危及生命的毒性发生率较高以及迟发效应的风险，未来应通过引入毒性最小的更有效治疗方式进一步限制甚至取消其适应症。该试验已在大学医院医学信息网络临床试验注册中心（UMIN-CTR）注册，注册号为#UMIN000004801。
