Pediatric blastic plasmacytoid dendritic cell neoplasm: report of four cases and review of literature.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with poor outcome. Four children with BPDCN treated at our hospital were enrolled. All the four cases presented with cutaneous lesions. Bone marrow and central nervous system was involved in 50% and 25% of patients, respectively. The whole exome sequencing analysis revealed that KMT2 family genes were the most frequently mutated (4/4, 100%), followed by IKZF2 (2/4, 50%). The point mutation p.D348N was found in three patients and one patient had p.C394Y mutation in the KMT2C gene. Translocation of KMT2A-MLLT3 was found in Case 2. Case 1 had complex karyotype, who was induced by acute myeloid leukemia-like regimens. Although he received allogeneic hematopoietic stem cell transplantation twice as well as CD123 chimeric antigen receptor T cell therapy, the disease still progressed and he died 37 months after diagnosis. The other three patients were treated with Interfant-99 protocol. They tolerated the therapy well without significant toxicities and now in complete remission so far with a median follow up time of 9 months. More studies are needed to address the question whether the complex karyotype and KMT2 family genes are the causes of the relapse and refractory in BPDCN.