Jentzsch Madlen, Bischof Lara, Brauer Dominic, Backhaus Donata, Ussmann Jule, Franke Georg-Nikolaus, Vucinic Vladan, Platzbecker Uwe, Schwind Sebastian
Medical Clinic and Policlinic 1, Hematology, Cellular Therapy and Hemostaseology, University of Leipzig Medical Center, 04103 Leipzig, Germany.
Cancers (Basel). 2023 Feb 18;15(4):1312. doi: 10.3390/cancers15041312.
Although the presence of -ITD, as well as levels of the -ITD allelic ratio, have been described as prognostic factors in acute myeloid leukemia (AML), little is known about how the -ITD allelic ratio impacts patients' outcomes when receiving an allogeneic hematopoietic stem cell transplantation (HSCT). We analyzed 118 patients (median age at diagnosis 58.3, range 14.3-82.3 years) harboring -ITD, of whom 94 patients were consolidated with an allogeneic HSCT and included in outcome analyses. A high -ITD allelic ratio was associated with a higher white blood cell count, higher blood and bone marrow blasts, and worse ELN2017 risk at diagnosis. Patients with a high -ITD allelic ratio more often had mutations, while patients with a low allelic ratio more often had -TKD mutations. Patients with a high -ITD allelic ratio were less likely to achieve a measurable residual disease (MRD)-negative remission prior to allogeneic HSCT and had a trend for a shorter time to relapse. However, there was no distinct cumulative incidence of relapse, non-relapse mortality, or overall survival according to the -ITD allelic ratio in transplanted patients. While co-mutated -TKD was associated with better outcomes, the MRD status at HSCT was the most significant factor for outcomes. While our data indicates that an allogeneic HSCT may mitigate the adverse effect of a high -ITD allelic ratio, comparative studies are needed to evaluate which -ITD mutated patients benefit from which consolidation strategy.
尽管-ITD的存在以及-ITD等位基因比例已被描述为急性髓系白血病（AML）的预后因素，但对于-ITD等位基因比例在接受异基因造血干细胞移植（HSCT）时如何影响患者的预后知之甚少。我们分析了118例携带-ITD的患者（诊断时中位年龄58.3岁，范围14.3 - 82.3岁），其中94例患者接受了异基因HSCT巩固治疗并纳入预后分析。高-ITD等位基因比例与诊断时较高的白细胞计数、较高的血液和骨髓原始细胞以及较差的ELN2017风险相关。高-ITD等位基因比例的患者更常发生 突变，而低等位基因比例的患者更常发生-TKD突变。高-ITD等位基因比例的患者在异基因HSCT前达到可测量残留病（MRD）阴性缓解的可能性较小，且有复发时间较短的趋势。然而，根据移植患者的-ITD等位基因比例，复发、非复发死亡率或总生存率没有明显的累积发生率。虽然共突变的-TKD与较好的预后相关，但HSCT时的MRD状态是影响预后的最显著因素。虽然我们的数据表明异基因HSCT可能减轻高-ITD等位基因比例的不良影响，但需要进行比较研究以评估哪些-ITD突变患者从哪种巩固策略中获益。
