University of Kansas Medical Center, Division of Hematologic Malignancies and Biomolecular Therapeutics, Kansas City, KS, United States.
University of Kansas Medical Center, Division of Hematologic Malignancies and Biomolecular Therapeutics, Kansas City, KS, United States.
Leuk Res. 2020 Aug;95:106402. doi: 10.1016/j.leukres.2020.106402. Epub 2020 Jun 18.
Chromosome 17 abnormalities, especially disorders of the 17p region and including TP53 gene mutations, result in very low rates of cure for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) treated with conventional chemotherapy or allogeneic hematopoietic cell transplant (allo-HCT). Our retrospective study analyzed outcomes in patients with chromosome 17 (ch17) abnormalities who received conventional chemotherapy followed by allo-HCT versus those who did not receive a transplant. We analyzed whether poor outcomes extend to patients with all types of ch17 abnormalities and the impact of concomitant TP53 gene mutations assessed by next-generation sequencing (NGS) on prognosis.
We retrospectively analyzed diagnostic and outcome data on 98 patients treated at our institution from 2012 to 2018 with AML or MDS who possessed ch17 abnormalities by cytogenetic analysis. The presence of TP53 mutations was analyzed by NGS. Primary endpoint of our study was overall survival (OS).
61 patients with AML and 37 with MDS were included. Complete remission (CR) with first line treatment was similar between induction chemotherapy or hypomethylating agents (HMA), 22.9 % versus 21.6 % (p = 0.33). Median OS for all patients (with or without transplant) was 10 months. Patients with abnormal ch17 in conjunction with any TP53 mutation(s) exhibited worse OS compared to patients without a TP53 mutation (10 versus 23 months, p = 0.02). 30 patients (19 AML, 11 MDS) underwent HCT, with a median OS of 11 months. For AML patients who underwent allo-HCT, 18 were in CR (13 with cytogenetic remission) and 1 had persistent disease at transplant. In the MDS cohort, 3 patients were in CR (2 with cytogenetic remission) and 8 had stable disease. Post allo-HCT survival of AML and MDS cohorts did not differ (p = 0.6), although cytogenetic CR at time of HCT trended towards improved OS (17 versus 8 months; p = 0.6).
AML/MDS patients with ch17 abnormalities have poor outcomes with or without HCT. Our results show that patients with ch17 abnormalities and TP53 mutations have a significantly poorer survival compared to patients who have ch17 abnormalities but no TP53 mutations. Drugs targeting abnormalities of the p53 pathway, improvement in depth of response prior to HCT, and novel maintenance strategies are needed for improved outcomes in these patients.
染色体 17 异常，特别是 17p 区域的异常，包括 TP53 基因突变，导致接受常规化疗或异基因造血细胞移植（allo-HCT）治疗的急性髓系白血病（AML）或骨髓增生异常综合征（MDS）患者的治愈率非常低。我们的回顾性研究分析了接受常规化疗后接受 allo-HCT 与未接受移植的染色体 17（ch17）异常患者的结局。我们分析了较差的结局是否扩展到具有各种 ch17 异常的患者，以及通过下一代测序（NGS）评估的同时存在的 TP53 基因突变对预后的影响。
我们回顾性分析了 2012 年至 2018 年在我们机构接受治疗的 AML 或 MDS 患者的诊断和结局数据，这些患者通过细胞遗传学分析存在 ch17 异常。通过 NGS 分析 TP53 突变的存在。我们研究的主要终点是总生存（OS）。
纳入了 61 例 AML 和 37 例 MDS 患者。一线诱导化疗或低甲基化剂（HMA）治疗的完全缓解（CR）率相似，分别为 22.9%和 21.6%（p=0.33）。所有患者（无论是否接受移植）的中位 OS 为 10 个月。与无 TP53 突变的患者相比，存在异常 ch17 并伴有任何 TP53 突变的患者 OS 更差（10 个月与 23 个月，p=0.02）。30 例（19 例 AML，11 例 MDS）接受了 HCT，中位 OS 为 11 个月。对于接受 allo-HCT 的 AML 患者，18 例处于 CR（13 例有细胞遗传学缓解），1 例在移植时仍有疾病。在 MDS 队列中，3 例处于 CR（2 例有细胞遗传学缓解），8 例病情稳定。AML 和 MDS 队列的 allo-HCT 后生存无差异（p=0.6），尽管移植时的细胞遗传学 CR 有改善 OS 的趋势（17 个月与 8 个月；p=0.6）。
AML/MDS 患者存在 ch17 异常时预后不良，无论是否进行 HCT 均如此。我们的结果表明，与存在 ch17 异常但无 TP53 突变的患者相比，存在 ch17 异常和 TP53 突变的患者的生存率显著降低。需要针对 p53 通路异常的药物、在 HCT 前提高反应深度以及新的维持策略，以改善这些患者的结局。
