Blastic plasmacytoid dendritic cell neoplasm with transient response to pralatrexate
Dear Editor, Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease which is recognized by the WHO in 2016, as a distinct entity and separately listed in the group of acute myeloid leukemias and related precursor neoplasms. BPDCN is characterized by the clonal proliferation of precursors of plasmacytoid dendritic cells, also known as professional type I interferon producing cells or plasmacytoid monocytes [1] The average age at diagnosis is 60 to 70 years with a male predominance and is characterized by an aggressive behavior despite the often indolent clinical presentation, with apparently isolated cutaneous involvement in almost all cases in the form of solitary or multiple lesions [2] A 77 year old male presented with multiple, asymptomatic, rapidly growing nodes, and plaques, which started on the forehead and arm (Fig. 1a) Additionally, he had a 6 month history of progressive thrombocytopenia. The peripheral blood showed a mild anemia (hemoglobin 134 g/l) with moderate thrombopenia (93 x 10e9/l) Lymphocyte counts were normal but morphologically forms with fine chromatin and indented nuclei were identifiable. The trephine biopsy of the bone marrow showed an interstitial and small nodular infiltration (approximately 40% of medium sized blasts with irregular nuclei. Flow cytometric analysis of the bone marrow identified a population positive for CD2, CD38, CD45, CD56, CD123, and negative for CD34, CD117, CD4, CD8, and CD19. The skin biopsy showed middle sized blasts with eccentric nuclei, irregular nuclear contours and small eosinophilic nucleoli in the dermis, sparing the epidermis (Fig. 1b e) These cells were positive for CD2, CD4, CD56, CD123, TCL1, and TdT and negative for CD3, CD5, CD7, CD11c, CD14, CD19, CD20, CD34, CD68, CD79a, CD117, and myeloperoxidase. A blastic plasmacytoid dendritic cell neoplasm (BPDCN) was diagnosed. Because of the advanced age the patients was treated with pralatrexate 15 mg/m intravenously once weekly. Although pretreated with Vitamin B12 subcutaneously a week prior, the patient suffered from mucositis grade 2 after the second application of pralatrexate. Pralatrexate was consequently reduced to 10 mg/m. In the following cycles, the cutaneous manifestations disappeared completely and the thrombocytopenia recovered to almost normal levels. After 5 cycles of pralatrexate, the patient suffered a leukemic relapse without evidence of cutaneous disease. The patient refused further therapy options and deceased few days later. There are no data or clinical trials that can define the best treatment for patients with BPDCN. In a retrospective study ALL/lymphoma type therapy treated patients had better survival outcomes than those who received AML type therapy [3] Despite sensitivity to initial chemotherapy, BPDCN are characterized by early, treatment resistant relapses and the prognosis is poor with median survival from 12 to 27 months. Allogeneic hematopoietic stem cell transplantation (HSCT) is also feasible and may result in sustained remission [4] Since our patient was not deemed to be fit enough for intensive treatment we decided to treat with pralatrexate that was favored by the patient over 5 azacytidine. Here, we report the application of pralatrexate as first line treatment in BPDCN Christian Arranto Christian.arranto@usb.ch
Annals of Hematology