Organ involvement in adults with BPDCN is associated with sun exposure history, TET2 and RAS mutations, and survival

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) can involve skin, bone marrow (BM), central nervous system (CNS), and non-CNS extramedullary sites. Preclinical models demonstrated clonal advantage of TET2-mutated plasmacytoid dendritic cells exposed to UV radiation. However, whether sun exposure, disease characteristics, and patient survival are clinically related is unclear. We classified 66 BPDCN patients based on organ involvement at diagnosis as skin only (n=19), systemic plus skin (n=33), or systemic only (n=14). BM involvement was absent, microscopic (<5%), or overt (≥5%). UV exposure history was based on clinical and demographic data. Patients with skin only BPDCN were more frequently ≥75 years (47% vs. 19%, p=0.032) and had lower rates of complex karyotype (0 vs. 32%, p=0.022) and mutated NRAS (0 vs. 29%, p=0.044). Conversely, those in the systemic only group had lower UV exposure (23% vs. 59%, p=0.03) and fewer TET2 mutations (33% vs. 72%, p=0.051). With median follow-up of 42 months, the median overall survival (OS) was 23.5, 20.4, and 17.5 months for skin only, systemic plus skin, and systemic only, respectively. Patients with no BM involvement had better OS vs. overt BM involvement (median OS 27.3 vs. 15.0 months, p=0.033) and comparable to those with microscopic BM involvement (27.3 vs. 23.5 months, p=0.6). Overt BM involvement remained significant for OS in a multivariable analysis adjusted for baseline characteristics and treatment. In summary, BPDCN clinical characteristics are associated with disease genetics and survival. These data are useful to estimate prognosis for individual patients and may indicate informative subtyping of BPDCN.