Senapati Jayastu, Loghavi Sanam, Garcia-Manero Guillermo, Tang Guillin, Kadia Tapan, Short Nicholas J, Abbas Hussein A, Arani Naszrin, DiNardo Courtney D, Borthakur Gautam, Pemmaraju Naveen, Oran Betul, Shpall Elizabeth, Popat Uday, Champlin Richard, Pierce Sherry, Arora Sankalp, Issa Ghayas, Yilmaz Musa, Patel Keyur, Takahashi Koichi, Montalban-Bravo Guillermo, Hammond Danielle, Haddad Fadi G, Ravandi Farhad, Kantarjian Hagop M, Daver Naval G
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Haematologica. 2025 Jun 1;110(6):1304-1315. doi: 10.3324/haematol.2024.286465. Epub 2024 Dec 12.
In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency (VAF) ≥40%; TP53 low-risk (TP53LR) included a single TP53 mutation VAF <40%. Four-hundred and thirteen patients (291 AML, 122 MDS) at a median age of 69.4 years were included, 350 (85%) with TP53HR (253 AML [87%], 97 [79%] MDS). Overall response (OR) rate was 53% in AML and 62% in MDS. OR and composite complete response (CRc) rates was similar in patients with AML irrespective of treatment intensity, but higher when treated with venetoclax. At a median follow-up of 77 months, median OS was superior in patients with MDS than AML (10.8 vs. 5.9 months). On multivariate analysis (MVA) MDS had lower hazards of death compared to AML, as was TP53LR and HSCT. In the AML cohort, TP53LR and HSCT were favorable on MVA, though venetoclax did not improve survival. Both the diagnosis of MDS or AML and burden of TP53 aberrations dictated outcomes in our analysis and HSCT consistently led to improved survival outcomes.
在伴有TP53畸变的骨髓增生异常综合征（MDS）和急性髓系白血病（AML）中，剖析患者、疾病和治疗因素之间的相互作用对于治疗决策和预后判断至关重要。这项回顾性分析纳入了在MD安德森癌症中心接受治疗的新诊断的MDS（原始细胞>5%）和伴有TP53突变的AML患者。我们考虑了患者年龄、TP53畸变负担、治疗强度以及AML亚组中维奈托克的使用情况，还有异基因造血干细胞移植（HSCT）来研究预后。如果存在>1个突变、1个突变加等位基因缺失或单个突变且变异等位基因频率（VAF）≥40%，则将TP53注释为高危（TP53HR）；TP53低危（TP53LR）包括单个TP53突变且VAF<40%。纳入了413例患者（291例AML，122例MDS），中位年龄为69.4岁，其中350例（85%）为TP53HR（253例AML[87%]，97例[79%]MDS）。AML的总体缓解（OR）率为53%，MDS为62%。无论治疗强度如何，AML患者的OR和复合完全缓解（CRc）率相似，但接受维奈托克治疗时更高。中位随访77个月时，MDS患者的中位总生存期优于AML（10.8个月对5.9个月）。多变量分析（MVA）显示，与AML相比，MDS的死亡风险较低，TP53LR和HSCT也是如此。在AML队列中，TP53LR和HSCT在MVA上具有优势，尽管维奈托克并未改善生存率。在我们的分析中，MDS或AML的诊断以及TP53畸变负担都决定了预后，并且HSCT始终能改善生存结果。
