A phase I clinical research study to test the safety and efficacy of a combination chemotherapy regimen consisting of methotrexate, L-asparaginase, idarubicin, and dexamethasone followed by allogenic or autologous bone marrow transplantation in 26 participants newly diagnosed with BPDCN is planned but not yet in its recruiting phase.While few studies have reported on the treatment of BPDCN that has recurred following initial therapy, donor lymphocyte infusions coupled with alternative chemotherapy treatments have induced second complete or partial remissions in a few patients. Tagraxofusp-erzs
Tagraxofusp-erzs (trade name Elzonris; formerly SL-401 and DT388-IL3) was approved in the United States in December 2018 for the treatment of BPDCN. Tagraxofusp-erzs is a fusion protein consisting of interleukin 3 (i.e. IL-3) fused to diphtheria toxin. The fusion protein readily kills cultured pDC by binding to their IL-3 receptors to thereby gain entrance to the cells and then blocking these cells protein synthesis (due to diphtheria toxin-mediated inhibition of eukaryotic elongation factor 2). Prognosis
Due to the high rates of recurrence following initial therapy and the short overall survival times of individuals with BPDCN, prognosis of the disease is poor. However, further study of treatment regimens that include intrathecal chemotherapy and hematological stem cell transplantation in initial treatment regimens (see previous section) and newer non-chemotherapeutic drug treatments (see next section) may improve this situation. Research
UCART123
UCART123 are chimeric T cell receptor-bearing cells, i.e. T lymphocytes engineered to bear a monoclonal antibody that directs them to attack and kill BPDCN cells.
CD123), CLEC4C, and Neuropilin, and 5) failure to express certain marker proteins that are commonly expressed by myeloid, lymphoid, and NK cell lineages.Blastic plasmacytoid dendritic cell neoplasm typically arises after the serial acquisition of multiple genetic abnormalities in pDC or their precursor cells. Inactivating mutations (i.e. mutations which cause the gene to make no or a less active product) in the TET2 gene are the most common genetic abnormality in the disease, occurring in 32–67% of all BPDCN cases and often accompanied by mutations in either the NPM1 or SRSF2 gene. Numerous other genetic abnormalities are associated with the disease: 1) mutations in NRAS, ASXL1, and TP53; 2) deletions of the CDKN2A-ARF-CDKN2B locus on the short arm of chromosome 9,  CDKN1B locus on the short arm of chromosome 12, RB1 locus on the long arm of chromosome 13, or NRC1 locus on the long arm of chromosome 5; 3) fusions of KMT2A on the long arm of chromosome 11 with MLLT1 on the short arm of chromosome 10, SUPT3H on the short arm of chromosome with MYC on the long arm of chromosome 8, or KMT2A on the long arm of chromosome 11 with MLLT1 on the long arm of chromosome 19; and 4) duplication or loss of entire chromosomes, particularly chromosomes 9, 13, or 15. Laboratory studies indicate that malignant pDC have a pathologically overactive NF-κB pathway that promotes their survival and production of various cytokines) that stimulate their own proliferation.