The incidence, risk factors, and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia (AML) have not been established yet. This study analyzed clinical and biological characteristics, the impact on prognosis, and the cumulative incidence of EMI in a monocentric retrospective series. All adult patients diagnosed with AML observed in our institution between January 2010 and December 2017 were included in the analysis. Overall, 346 AMLs were analyzed. The incidence of EMI was 11% (38 patients). The involved sites were: skin (66%), central nervous system (CNS) (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most patients (91%) had only one EMI site, while 9% had multiple sites affected at the same time. Twenty-four (63%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 10 patients (26%); 4 patients had EMI both at presentation and relapse. EMI had a significantly higher frequency in patients with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), CD117-negative (p=0,03) at flow cytometry analysis, MLL rearrangements (p=0.001), trisomy 8 (p=0,02). An analysis regarding treatment, overall survival (OS), and disease-free survival (DFS) was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient receiving best supportive care was excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 patients), hypomethylating agents (5 patients), and low dose cytarabine (1 patient); 8 patients only (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). After induction therapy, complete remission (CR) rate was 22%, with a median DFS of 7.4 months. The median OS of all 27 EMI patients was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI patients who undergone allo-HSCT than those (19 patients) who did not receive this procedure (16.7 vs. 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for our population's survival (p<0,0001). This study confirms the poor prognosis for EMI patients. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in these patients' therapeutic approach, being associated with a better prognosis.

中文翻译：

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急性髓系白血病的髓外受累。单一中心十年经验。

成人急性髓系白血病 (AML) 患者髓外受累 (EMI) 的发生率、危险因素和预后意义尚未确定。本研究通过单中心回顾性系列分析了 EMI 的临床和生物学特征、对预后的影响以及 EMI 的累积发生率。2010 年 1 月至 2017 年 12 月期间在我们机构观察到的所有诊断为 AML 的成年患者均纳入分析。总体而言，分析了 346 个 AML。EMI 发生率为 11%（38 名患者）。受累部位为：皮肤（66%）、中枢神经系统（CNS）（23%）、胸膜（7%）、淋巴结（5%）、腹膜（2%）、脾脏（2%）、胰腺（2 %）、乳房（2%）和骨头（2%）。大多数患者 (91%) 只有一个 EMI 部位，而 9% 的患者有多个部位同时受到影响。24 名患者 (63%) 就诊时表现出 EMI 体征，10 名患者 (26%) 出现髓外复发；4 名患者在就诊时和复发时均出现 EMI。在单核细胞和粒单核细胞白血病亚型 (p<0.0001)、流式细胞术分析中 CD117 阴性 (p=0.03)、MLL 重排 (p=0.001)、8 三体性患者中，EMI 发生频率显着较高。 p=0,02)。仅对 28 名在发病时经历 EMI 的患者进行了有关治疗、总生存期 (OS) 和无病生存期 (DFS) 的分析；一名接受最佳支持治疗的 EMI 患者被排除在 OS 分析之外。其余27例患者接受常规化疗（21例）、低甲基化药物（5例）、小剂量阿糖胞苷（1例）；仅 8 名患者 (28.5%) 接受了同种异体干细胞移植 (allo-HSCT)。诱导治疗后，完全缓解（CR）率为22%，中位DFS为7.4个月。所有 27 名 EMI 患者的中位 OS 为 11.6 个月（范围 2-79）；这导致 8 名接受异基因 HSCT 的 EMI 患者比未接受该手术的患者（19 名患者）的存活时间明显更长（分别为 16.7 个月和 8.2 个月，p=0.02）。单变量和多变量分析表明，接受异基因造血干细胞移植和达到 CR 是我们人群生存的主要积极预后因素 (p<0,0001)。这项研究证实了 EMI 患者的预后不良。Allo-HSCT 虽然仅适用于某些情况，但似乎在这些患者的治疗方法中发挥着至关重要的作用，与更好的预后相关。