Diagnostic and Therapeutic Advances in Blastic Plasmacytoid Dendritic Cell Neoplasm: A Focus on Hematopoietic Cell Transplantation

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an exceedingly rare disorder categorized under acute myeloid leukemia by the World Health Organization. Phenotypically, malignant cells coexpress CD4(+) and CD56(+) without coexpressing common lymphoid or myeloid lineage markers. BPDCN frequently expresses CD123, TCL1, BDCA-2, and CD2AP. Restriction of CD2AP expression to plasmacytoid dendritic cells makes it a useful tool to help confirm diagnosis. Clonal complex chromosome aberrations are described in two-thirds of cases. Eighty percent of BPDCN cases present with nonspecific dermatological manifestations, prompting inclusion in the differential diagnosis of atypical skin rashes refractory to standard treatment. Prognosis is poor, with a median survival of less than 18 months. No prospective randomized data exist to define the most optimal frontline chemotherapy. Current practice considers acute myeloid leukemia-like or acute lymphoblastic leukemia-like regimens acceptable for induction treatment. Unfortunately, responses are short-lived, with second remissions difficult to achieve, underscoring the need to consider hematopoietic cell transplantation early in the disease course. Allografting, especially if offered in first remission, can result in long-term remissions. Preclinical data suggest a potential role for immunomodulatory agents in BPCDN. However, further research efforts are needed to better understand BPDCN biology and to establish evidence-based treatment algorithms that might ultimately improve overall prognosis of this disease.

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10‐Color flow cytometry diagnosis and HyperCVAD therapy

“…Chemotherapy with AML-type, acute lymphoblastic leukemia (ALL)-type or non-Hodgkin lymphoma-like regimens can yield complete remission (CR) rates of 40-90% [7,8]. Treatment with ALL-type regimens is associated with higher CR rates and/or overall survival (OS) [7,9,10].…”

“…Treatment with ALL-type regimens is associated with higher CR rates and/or overall survival (OS) [7,9,10]. However, remissions are usually short term with a median OS of 12-18 months [8]. Recent data suggest that the median OS of patients who received an allogeneic-Hematopoeitic Cell Transplant (allo-HCT) were superior to those who received chemotherapy alone (22.7 months vs. 7.1 months; P 5 0.03) [7].…”

Treatment of blastic plasmacytoid dendritic cell neoplasm

“…Unfortunately, prospective series of chemotherapy in BPDCN are lacking. We direct the reader to a series of comprehensive retrospective chemotherapy reviews (more than 4 patients per series) in Pagano et al, 31 Kharfan-Dabaja et al, 37 and most recently Laribi et al 36 We have not re-created the information contained in these articles, but we have proon thr basis of comorbidity and transplant eligibility, as shown in Figure 2. When deciding which therapy is most appropriate, it is important to remember that, although those with early-stage and isolated cutaneous lesions often have very good performance status, the majority of patients have advanced disease (stage III to IV) as defined by Ann Arbor staging and a median age older than 60 years at diagnosis.…”

Long-term survival following autologous and allogeneic stem cell transplantation for blastic plasmacytoid dendritic cell neoplasm

“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative conditioning (MAC) during remission has shown encouraging results for patients with BPDCN. 3,[12][13][14][15][16][17] Meanwhile, only a few small case series were described that showed the benefit of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) or reduced-intensity conditioning (RIC) allo-HSCT. 12,14,15,18,19 Because BPDCN is a disease of advanced age, clarifying the role of the RIC regimen or auto-HSCT in BPDCN is crucial.…”