ALK 阴性间变大细胞淋巴瘤伴基因重排具有独特的疾病特征，无进展生存更好：LYSA 研究。
ALK-negative anaplastic large cell lymphoma with rearrangement has distinctive disease characteristics with better progression-free survival: a LYSA study.
机构信息
Lymphoid Malignancies Department, Henri-Mondor University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), 94000 Créteil, France; Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil.
Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and Lausanne University.
出版信息
Haematologica. 2023 Jun 1;108(6):1590-1603. doi: 10.3324/haematol.2022.281442.
ALK-negative anaplastic large cell lymphoma (ALCL) comprises subgroups harboring rearrangements of DUSP22 (DUSP22- R) or TP63 (TP63-R). Two studies reported 90% and 40% 5-year overall survival (OS) rates in 21 and 12 DUSP22-R/TP63- not rearranged (NR) patients, respectively, making the prognostic impact of DUSP22-R unclear. Here, 104 newly diagnosed ALK-negative ALCL patients (including 37 from first-line clinical trials) from the LYSA TENOMIC database were analyzed by break-apart fluorescence in situ hybridization assays for DUSP22-R and TP63-R. There were 47/104 (45%) DUSP22-R and 2/93 (2%) TP63-R cases, including one DUSP22-R/TP63-R case. DUSP22-R tumors more frequently showed CD3 expression (62% vs. 35%, P=0.01), and less commonly a cytotoxic phenotype (27% vs. 82%; P<0.001). At diagnosis, DUSP22- R ALCL patients more frequently had bone involvement (32% vs. 13%, P=0.03). The patient with DUSP22-R/TP63-R ALCL had a rapidly fatal outcome. After a median follow-up of 4.9 years, 5-year progression-free survival (PFS) and OS rates of 84 patients without TP63-R treated with curative-intent anthracycline-based chemotherapy were 41% and 53%, respectively. According to DUSP22 status, 5-year PFS was 57% for 39 DUSP22-R versus 26% for 45 triple-negative (DUSP22-NR/TP63-NR/ALK-negative) patients (P=0.001). The corresponding 5-year OS rates were 65% and 41%, respectively (P=0.07). In multivariate analysis, performance status and DUSP22 status significantly affected PFS, and distinguished four risk groups, with 4-year PFS and OS ranging from 17% to 73% and 21% to 77%, respectively. Performance status but not DUSP22 status influenced OS. The use of brentuximab vedotin in relapsed/refractory patients improved OS independently of DUSP22 status. Our findings support the biological and clinical distinctiveness of DUSP22- R ALK-negative ALCL. Its relevance to outcome in patients receiving frontline brentuximab vedotin remains to be determined.
ALK 阴性间变大细胞淋巴瘤（ALK-N）包括存在 DUSP22（DUSP22-R）或 TP63（TP63-R）重排的亚组。两项研究分别报道了 21 例和 12 例 DUSP22-R/TP63-NR 患者的 5 年总生存率（OS）为 90%和 40%，这使得 DUSP22-R 的预后影响仍不清楚。在此，我们对 LYSA TENOMIC 数据库中的 104 例新诊断的 ALK-N ALCL 患者（包括 37 例来自一线临床试验的患者）进行了 DUSP22-R 和 TP63-R 的分离荧光原位杂交分析。47/104（45%）例患者存在 DUSP22-R，2/93（2%）例患者存在 TP63-R，包括 1 例 DUSP22-R/TP63-R 患者。DUSP22-R 肿瘤更常表达 CD3（62% vs. 35%，P=0.01），较少表现为细胞毒性表型（27% vs. 82%；P<0.001）。在诊断时，DUSP22-R ALCL 患者更常出现骨受累（32% vs. 13%，P=0.03）。携带 DUSP22-R/TP63-R ALCL 的患者有快速致命的结局。中位随访 4.9 年后，接受根治性蒽环类药物为基础的化疗的 104 例无 TP63-R 患者的 5 年无进展生存（PFS）和 OS 率分别为 41%和 53%。根据 DUSP22 状态，39 例 DUSP22-R 患者的 5 年 PFS 为 57%，而 45 例三阴性（DUSP22-NR/TP63-NR/ALK-N）患者的 5 年 PFS 为 26%（P=0.001）。相应的 5 年 OS 率分别为 65%和 41%（P=0.07）。多因素分析显示，表现状态和 DUSP22 状态显著影响 PFS，并区分了四个风险组，4 年 PFS 和 OS 分别为 17%至 73%和 21%至 77%。表现状态而非 DUSP22 状态影响 OS。在复发性/难治性患者中使用 Brentuximab Vedotin 可改善 OS，独立于 DUSP22 状态。我们的研究结果支持 DUSP22-R ALK-N ALCL 的生物学和临床独特性。其在接受一线 Brentuximab Vedotin 治疗的患者中的相关性仍有待确定。
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