Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm: How to Treat?
We read with great interest the report by Hama et al1 about plasmacytoid dendritic cell leukemia in children. We hereby report our own experience on this extremely rare and aggressive neoplasm.
A 4-year-old female was first seen at a rheumatology department because of a 6-month history of migratory polyarthralgia and nonpruriginous papulas on her chest, back, and legs. She had undergone a knee sinovectomy and a course of corticoid therapy with transient clinical. In the course of the investigation, a skin biopsy was performed and it revealed a dermal and subcutaneous neoplasic infiltrate of round cells,CD45+,CD4+,CD56+,CD68+,CD11c+,Cd117+,CD15−, MPX−, CD34+, and CD20+, compatible with blastic plasmacytoid dendritic cell neoplasm (BPDCN). Bone marrow (BM) examination showed a pathologic population of 64% with an immunophenotype of dendritic cells and G-banding analysis of BM cells revealed a complex karyotype with del(3)(q12∼13q27), del(7)(p13p21), del(11)(q14q23), −18, −20,+2mar[cp9]/46,XX. Cerebrospinal fluid cytology showed no evidence of involvement by malignant cells. Induction treatment with INTERFANT-99 protocol2 was initiated and complete remission (CR) was achieved after induction therapy (both skin lesions and BM involvement). However, on day 30 of induction therapy she developed septic shock with bilateral pneumonia by metapneumovirus and acute respiratory distress syndrome, requiring vasopressor support and invasive ventilation. She developed progressive respiratory failure with bilateral pneumothorax and, despite all the measures, she died in CR.
BPDCN is a rare, aggressive tumor, which primarily affects the elderly.3 The overall prognosis in adults is poor, with a reported median overall survival (OS) of 8.7 months.4 Even though there is lack of consensus regarding the optimal treatment approach, acute lymphoblastic leukemia (ALL)/lymphoma-type therapies with CNS prophylaxis and hematopoietic stem cell transplant hematopoietic stem cell transplant (HSCT) in first CR seem to be a justified option.4–6
Childhood BPDCN might represent a different subset of the disease, characterized by a less frequent cutaneous involvement and a better prognosis.7 A review of 25 pediatric BPDCN cases, most of these treated with high-risk-ALL or non-Hodgkin lymphoma protocols, without HSCT, reported an OS of 72% with a median follow-up of 30 months.7 In another analysis of published data, the 3-year OS in 32 published pediatric cases was 57.4%±10.9%.7 Both studies found that skin involvement was associated with worse outcome, prompting Sakashita et al8 to suggest HSCT in first CR following ALL induction regiment for children with BPDCN with cutaneous manifestation. Blastic dendritic neoplasic cells seem to be initially chemosensitive to active agents against lymphoblasts, but their myeloid lineage derivation may suggest that addiction of “myeloid strategies,” such as cytarabine, could be useful to improve outcome. Considering this rationale, the paucity of data, and lack of consensus regarding the optimal treatment approach, we report a treatment option using a protocol initially designed for infants under 1 year with ALL or biphenotypic leukemia.2
Conclusions from published cases in the literature carry several biases and are often more optimistic than real-life experience as poor outcome cases are less often reported. Larger numbers are required and a central registry would be an option to consider.