Treatment of blastic plasmacytoid dendritic cell neoplasm

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4⁺CD56⁺CD123⁺lineage^-MPO^-, although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies. Chromosomal aberrations are frequent, and the mutational landscape of BPDCN is being rapidly characterized although no obvious molecular target for chemoimmunotherapy has been identified. Chemotherapy regimens developed for acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome have all been used to treat BPDCN. Relapse is frequent, and overall survival is quite poor. Allogeneic transplantation offers a chance at prolonged remission and possible cure for those who are eligible; unfortunately, relapse remains high ranging from 30% to 40%. Novel therapies such as SL-401, a diphtheria toxin conjugated to interleukin-3 (IL-3) is commonly overexpressed in BPDCN and other aggressive myeloid malignancies and has shown considerable promise in ongoing clinical trials. Future work with SL-401 will define its place in treating relapsed or refractory disease as well as its role as a first-line therapy or bridge to transplantation.

Figure 1.

Morphologic evaluation and immunohistochemical markers that aid in the diagnosis of BPDCN. (A) Skin lesions of BPDCN can vary in shape, size, color, and distribution. Hyperpigmented red-brown macules, shown here, may be confused with neoplastic and nonneoplastic etiologies. (B) Skin biopsy (×500) of dermal infiltrate of immature mononuclear cells, which spares the epidermis (separated by a Grenz zone) typical of BPDCN, LC, and myeloid sarcoma (MS) and helps distinguish those diseases from mycosis fungoides which is usually epidermotropic. (C) Bone marrow aspirate (×1000) demonstrates medium to large cells with scant cytoplasm, immature chromatin, irregular nuclear contours, and prominent nucleoli. (D) Shared immunohistochemical markers are shown with a range of positive cases observed for BPDCN and AML/LC/MS. Ranges are rounded to the nearest 5% based on multiple series.^,,, Clearly the overlap of shared markers and exception of atypical cases that lack a particular marker highlight the need for review of unique markers to differentiate BPDCN from AML/LC/MS.

Figure 2.

BPDCN treatment algorithm. Aggressive therapy, including allogeneic SCT, should be considered for all patients who have the performance status and comorbidity scores to support this rigorous process. Early referral for clinical trial is warranted and encouraged. We prefer to lead with an AML regimen; given the high rate of CNS relapse, intrathecal therapy (IT) is strongly recommended. CCI, Charlson Comorbidity Index; MTX, methotrexate.