Search Results (3)

Blastic plasmocytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy, characterized by the involvement of multiple organs, including the skin, bone marrow and blood, lymph nodes and the central nervous system. According to tumor location, the disease is classified as skin-only, systemic-only, and skin and systemic. The cutaneous manifestations of disease are typical and are represented by violaceous single tumors or multiple plaques present in sun-exposed cutaneous areas. BPDCN is issued from the malignant transformation of dendritic cell progenitors and is diagnosed using the classical immunophenotypes CD123, CD4 and CD56 in addition to specific membrane markers of plasmocytoid dendritic cells. BPDCN is an aggressive disease and is associated with a short survival. Upfront therapies involve either chemotherapy regimens in fit patients and CD123-targeted therapies, including interleukin-3 conjugated with diphtheria toxin (Tagraxofusp, SL-401), or Pivekimab sunirine, an anti-IL-3R-drug conjugate, for both fit and unfit patients. Targeted treatments limit the toxicities of chemotherapy and allow the bridging of a consistent proportion of patients to hematopoietic stem cell transplantation, the only treatment associated with potential long-term survival. Full article

Blastic Plasmacytoid Dendritic Cell Neoplasms (BPDCNs) are a rare, highly aggressive hematological malignant neoplasm that primarily involve the skin, bone marrow, lymph nodes and even extra-nodal sites. The rarity and relative poor description of cases in the literature make it necessary to review and further studies that deeply investigate this entity not only in a histopathological but also molecular field. In August–September 2023, we searched MEDLINE, PubMed and Scopus for randomized controlled trials (RCTs), narrative and systematic reviews, meta-analyses, observational studies (either longitudinal or retrospective), and case series published in English in the last 25 years using the keywords BPDCN, PDCs, Blastic NK-cell lymphoma, agranular CD4+ NK leukemia/lymphoma, agranular CD4+ CD56+ hematodermic neoplasm/tumor. Despite the progress made in recent years in the diagnosis and biological understanding of the disease, until 2018 there was no clear consensus regarding its treatment and the main therapeutic schemes used were based on chemotherapy regimens already used in the treatment of lymphomas, acute lymphoblastic leukemia (ALL) and/or acute myeloid leukemia (AML). In this narrative review, we address the definition and epidemiological features of BPDCN, provide the different theories on the etiopathogenesis with particular attention to the presumed cell of origin, discuss the main clinical manifestations that provide a sign of its presence, summarize the main histopathological and immunophenotypic characteristics with special attention to the most important markers, and finally, we provide some of the most effective information on the therapeutic treatment modalities of BPDCN. Full article

In spite of consistent progress at the level of basic research and of clinical treatment, acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. To improve the outcomes of these patients, it is necessary to identify new therapeutic targets. IL3RA (CD123, alpha subunit of the interleukin 3 receptor) is a cell membrane protein overexpressed in several hematologic malignancies, including AML blastic plasmocytoid dendritic cell neoplasms (BPDCN). Given the higher expression of CD123 on leukemic cells compared to normal hematopoietic cells and its low/absent expression on normal hematopoietic stem cells, it appears as a suitable and attractive target for therapy. Various drugs targeting CD123 have been developed and evaluated at clinical level: interleukin-3 conjugated with diphtheria toxin; naked neutralizing anti-CD123 antibodies; drug–antibody conjugates; bispecific antibodies targeting both CD123 and CD3; and chimeric antigen receptor (CAR) T cells engineered to target CD123. Some of these agents have shown promising results at the clinical level, including tagraxofusp (CD123 conjugated with diphtheria toxin) for the treatment of BPDCN and IMGN632 (anti-CD123 drug-conjugate), and flotetuzumab (bispecific anti-CD123 and anti-CD3 monoclonal antibody) for the treatment of AML. However, the therapeutic efficacy of CD123-targeting treatments is still unsatisfactory and must be improved through new therapeutic strategies and combined treatments with other antileukemic drugs. Full article