Yisraeli Salman Meira, Terry Alexander R, Derkach Andriy, Nemirovsky David, Chin Kuo-Kai, Valtis Yannis K, Boussi Leora, Spivey Theresa, Xiao Wenbin, Famulare Christopher, Ciervo Jenna, Rowe Jacob M, Tallman Martin S, Stein Eytan M
Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel.
Blood Adv. 2025 Jul 8;9(13):3213-3222. doi: 10.1182/bloodadvances.2024015324.
The utility of a midcycle bone marrow biopsy (BMB) for early assessment of response in patients with acute myeloid leukemia (AML) after intensive chemotherapy (IC) induction is contested. Even when challenged, there is little consideration as to the possibility of different response dynamics among genetically defined subgroups. Clinical observations led to the hypothesis that patients with AML and mutations in IDH2-R172 (R172-m) exhibit particularly slow blast reduction after IC induction. The purpose of this study was to analyze response kinetics of patients with R172-m to IC and compare the dynamics to patients with AML and IDH2-R140 mutations (R140-m). A retrospective single-center analysis was conducted among patients with newly diagnosed IDH2-mutated AML who received IC induction. Dynamics of blast reduction were compared and correlated with outcomes. A total of 52 patients were identified; 33 with R140-m and 19 with R172-m. Patients with R172-m had significantly higher midcycle BMB median blast count (70% vs 5%; P < .001), and their BMBs were slightly more cellular (P = .045). Among the R140-m, 58% had ≤5% blasts vs 0 of the R172-m. Furthermore, it took significantly longer for patients with R172-m to achieve blast clearance (≤5% blasts in BMB) compared to those with R140-m (P = .017). However, there was no difference in overall survival between the 2 groups, and outcomes were similar and favorable. This type of slow blast reduction has only previously been described in patients with acute promyelocytic leukemia. These findings suggest judicial application of reinduction strategies in this subgroup and warrant further investigation.
对于强化化疗（IC）诱导后急性髓系白血病（AML）患者，周期中期骨髓活检（BMB）用于早期评估反应的效用存在争议。即便受到质疑，对于基因定义亚组间不同反应动态的可能性也几乎未加考虑。临床观察得出一个假设，即患有AML且IDH2-R172发生突变（R172-m）的患者在IC诱导后原始细胞减少特别缓慢。本研究的目的是分析R172-m患者对IC的反应动力学，并将其动态与患有AML且IDH2-R140发生突变（R140-m）的患者进行比较。对接受IC诱导的新诊断IDH2突变型AML患者进行了一项回顾性单中心分析。比较了原始细胞减少的动态，并将其与预后相关联。共确定了52例患者；33例为R140-m，19例为R172-m。R172-m患者的周期中期BMB原始细胞中位数显著更高（70%对5%；P <.001），且其BMB细胞含量略多（P =.045）。在R140-m患者中，58%的患者原始细胞≤5%，而R172-m患者中这一比例为0。此外，与R140-m患者相比，R172-m患者达到原始细胞清除（BMB中原始细胞≤5%）所需的时间显著更长（P =.017）。然而，两组的总生存期无差异，预后相似且良好。这种原始细胞缓慢减少的情况此前仅在急性早幼粒细胞白血病患者中有所描述。这些发现提示在该亚组中谨慎应用再诱导策略，并且值得进一步研究。
