Blastic plasmacytoid dendritic cell neoplasm: a comprehensive review in pediatrics, adolescents, and young adults (AYA) and an update of novel therapies

Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can involve the bone marrow, peripheral blood, skin, lymph nodes, and the central nervous system. Though more common in older adults, BPDCN has been reported across all age groups, including infants and children. The incidence of pediatric BPDCN is extremely low and little is known about the disease. Pediatric BPDCN is believed to be clinically less aggressive but often with more dissemination at presentation than adult cases. Unlike adults who almost always proceed to a hematopoietic stem cell transplantation in first complete remission if transplant-eligible, the majority of children can be cured with a high-risk acute lymphoblastic leukemia-like regimen. Hematopoietic stem cell transplantation is recommended for children with high-risk disease, the definition of which continues to evolve, or those in relapse and refractory settings where outcomes continue to be dismal. Novel agents used in other hematologic malignancies and CD123 targeted agents, including chimeric antigen receptor T-cells and monoclonal/bispecific antibodies, are being brought into research and practice. Our goal is to provide a comprehensive review of presentation, diagnosis, and treatment by review of pediatric cases reported for the last 20 years, and a review of novel targeted therapies and therapies under investigation for adult and pediatric patients.

A systematic literature review of 74 Chinese blastic plasmacytoid dendritic cell neoplasm patients

“…These actions are essential for accurately assessing the occurrence and progression of CNS disease in pediatric patients. 17 Although the CNS has been indicated in numerous studies as a possible sanctuary for tumor cells and a common site for recurrence, 18 there appeared to be no link between central nervous system infiltration and the disease’s relief or recurrence in our study. This might result from insufficient standardization in the examination and treatment of nervous system infiltration or limited numbers of cases.…”

“…This is the reason for the lingering uncertain regarding the role of HSCT and its optimal timing in pediatric patients with BPDCN. 17 Due to the limited number (three cases) of patients who received auto-HSCT, we were unable to determine if there existed a substantial discrepancy between allogeneic and autologous HSCT.…”

Efficacy and manageable safety of tagraxofusp in blastic plasmacytoid dendritic cell neoplasm: a case series of pediatric and adolescent/young adult patients

“…In this series, seven of the eight patients (88%) are female. Other publications, including a 2017 literature review of 74 pediatric patients found that 33 of 74 (45%) patients were female [9], and a review of 69 BPDCN cases in patients aged ≤21 years found the cases were evenly split between genders [30]. While the clinical presentation of BPDCN is similar between pediatric/AYA and adult patients, reported observations indicate that the biology of cancers may differ by age [31].…”

“…This is consistent with the age distribution reported in a review of 69 cases of BPDCN in patients aged ≤21 years for whom the mean age was 10 and most patients were older than 5. [30] In contrast, ALL has a reported peak incidence between 1-4 years of age [34] underscoring BPDCN's unique biology.…”

Flow Cytometry Profiling of Plasmacytoid Dendritic Cell Neoplasms

“…A subset of AML cases, especially those with monocytic features, may rarely exhibit a pDC-like immunophenotype with strong and homogeneous CD4, CD56 and CD123 expression, mimicking BPDCN [ 31 , 32 , 33 ]. Although cutaneous involvement is a characteristic feature of BPDCN, BPDCN with a leukemic presentation at onset without cutaneous involvement is an established phenomenon [ 34 , 35 , 36 ] that occurs in about 7% of BPDCN cases [ 13 ].…”