Blastic plasmacytoid dendritic cell neoplasm (BPDCN)

  • Method:
  • Anticoagulant:
  • Recommendation:
  • Method:
    Cytomorphology
  • Anticoagulant:
    EDTA
  • Recommendation:
    obligatory
  • Method:
    Immunophenotyping
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory
  • Method:
    Chromosome analysis
  • Anticoagulant:
    Heparin
  • Recommendation:
    obligatory
  • Method:
    FISH
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    facultative
  • Method:
    Molecular genetics
  • Anticoagulant:
    EDTA or Heparin
  • Recommendation:
    obligatory

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive malignant disease with rapid systemic spread (Swerdlow et al. 2017). The disease occurs mainly in older adults, rarely children are also affected. The latter show milder clinical courses than adults (Jegalian et al. 2010). Blastic plasmacytoid dendritic cell neoplasm accounts for only about 0.4% of all haematological neoplasias (Bueno et al. 2004, Pagano et al. 2013), the exact incidence is unknown, but men are three times more likely to develop the disease than women (Swerdlow et al. 2017).

Most frequent are initially indolent courses with multiple skin lesions. The skin manifestation is sometimes accompanied by a manifestation of lymph nodes or bone marrow involvement. The extent of bone marrow infiltration varies greatly and results in cytopenia, especially thrombocytopenia (Feuillard et al. 2002, Pagano et al. 2013). Rarely do patients show symptoms as in acute leukemia with systemic involvement without skin manifestation (Rauh et al. 2012).

Classification of Blastic plasmacytoid dendritic cell neoplasm

Formerly assigned to acute leukemias, BPDCN is listed as a separate entity in the new WHO classification 2017. Blastic plasmacytoid dendritic cell neoplasm is associated with a clonal proliferation of immature precursors of plasmacytoid dendritic cells. Whether these are cells of the myeloid or lymphatic series has been controversially discussed for years (Sapienza et al. 2019). Blastic plasmacytoid dendritic cell neoplasm may also occur in association with other myeloid diseases (CMML, MDS and AML) as well as in therapy-associated carcinomas and lymphomas (Swerdlow et al. 2017, Pagano et al. 2013).

Blastic plasmacytoid dendritic cell neoplasm - Diagnostics

Prognosis of Blastic plasmacytoid dendritic cell neoplasm

Although the majority of patients initially respond to chemotherapy, relapses are very frequent and survival time is short, averaging only 12-14 months (Pagano et al. 2013, Menezenes et al. 2014).

Therapy of Blastic plasmacytoid dendritic cell neoplasm

To date, no standardized therapy for blastic plasmacytoid dendritic cell neoplasm has been established. Currently, chemotherapy protocols for both myeloid and lymphatic acute leukemias (in individual cases also analogous lymphoma protocols), possibly followed by allogeneic stem cell transplantation, are used for patients requiring intensive therapy (Aoki et al. 2015, Pagano et al. 2013, Tzankov et al. 2017, Swerdlow et al. 2017). A consolidating autologous stem cell transplantation also seems promising (Aoki et al. 2015).

Targeted approaches could expand the therapeutic arsenal for blastic plasmacytoid dendritic cell neoplasm in the future. For example, the interleukin-3 receptor (CD123) is a suitable target due to its overexpression. Tagraxofusp, a fusion protein consisting of diphtheria toxin coupled to IL3 (Frankel et al. 2014), was approved by the FDA (FDA press release 2018) after a Phase II study and also holds the European marketing authorization for the treatment of BPDCN since January 2021 (EMA 2021). Under therapy with Tagraxofusp, response rates of 90% in previously untreated blastic plasmacytoid dendritic cell neoplasm and 67% in patients with previous therapy were achieved (Pemmaraju et al. 2019).  

Gene expression and immunohistochemical analyses have shown an aberrant activation of the NF-kB signaling pathway in blastic plasmacytoid dendritic cell neoplasm. These genes, as already successfully tested ex vivo and in the xenograft mouse model, could represent a further target structure for specific therapies in the future (Sapienza et al. 2014, Phillipe et al. 2017).

In addition, hypomethylating agents as well as BET inhibitors are currently in preclinical testing (Ceribelli et al. 2016, Emadali et al. 2016, Sapienza et al. Cancer 2019 and Haematologica 2019, Lezama & Ohgami 2019), and the use of the BCL2 inhibitor Venetoclax is also being evaluated in a clinical phase I study (NCT03485547).

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