Blastic plasmacytoid dendritic cell neoplasm: update on therapy especially novel agents

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. Most patients present with asymptomatic skin lesions as the first symptom and has a high frequency of bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co-expression without common lymphoid or myeloid lineage markers. There is no consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive to chemotherapy but the median event-free survival is very short. Allogeneic stem cell transplantation may improve the prognosis of BPDCN but the rate of relapse is still high. There are no specific targeted agents approved for patients with BPDCN, but advances in the understanding of the pathobiology of BPDCN and the results of early clinical studies have revealed novel targets and potentially effective agents. Novel targeted therapies may improve outcomes for patients with BPDCN in the future.

Blastic plasmacytoid dendritic cell neoplasm in the background of myeloproliferative disorder and chronic lymphocytic leukaemia

“…Regimens for AML/ALL like hyper-CVAD, methotrexate and cytarabine, lymphoma chemotherapies like CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHEOP (CHOP plus etoposide) may be effective 1 7 8 15 16. CNS prophylaxis using intrathecal therapy is highly recommended for BPDCN given the high risk of CNS involvement especially in relapses 1 7 8 15 16. Newer modalities include agents like venetoclax which is a BCL2 inhibitor effective in BPDCN 7 17.…”

“…Two main patterns of presentation are ‘dermatopathic’ (>90%), with indolent skin lesions followed by tumour dissemination, and ‘leukaemic’, with systemic involvement from the very beginning 2. Although exceedingly rare, a number of sites of involvement have been reported in different case studies including bone marrow, lymph nodes, central nervous system (CNS), spleen, liver, lungs, pleura, mucosa of oral cavity, tonsils, paranasal sinuses, eyes, breasts, tongue, kidneys, muscles and even gall bladder 5–89…”

Cladribine‐based salvage regimen‐induced deep remission of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in leukemia phase

“…For the RUNX1 mutation, studies have revealed that in the adoption of a preclinical BPDCN mouse model, the combination of the classical demethylation drugs 5′‐azacytidine and decitabine resulted in effects of controlling disease progression, lead to a potential epigenetic inhibitor for RUNX1 mutation.…”

“…NGS revealed detailed information of RUNX1 mutation For the RUNX1 mutation, studies have revealed that in the adoption of a preclinical BPDCN mouse model, the combination of the classical demethylation drugs 5′-azacytidine and decitabine resulted in effects of controlling disease progression, lead to a potential epigenetic inhibitor for RUNX1 mutation7,8 .On the other hand, cladribine significantly modified the ratio of myeloid DCs to plasmacytoid DCs, B lymphocyte CD19 + cells have significantly decreased, and there were vital changes in CD4 + cells, CD8 + cells, and CD3 + , This population produced large amounts of interferon alfa (IFN-α), which could lead to the death of tumor cells.…”

Diabetic ketoacidosis following PEG-asparaginase therapy

“…BPDCN is a rare and aggressive hematopoietic malignancy, which is highly responsive to chemotherapy treatment for ALL and not to CHOP therapy (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) (4). Prior to starting treatment, patient was given a glucometer and advised to check blood glucose at least twice a day for close monitoring.…”