Abstract
Background: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an underdiagnosed rare disease with poor outcomes and limited treatment options. The main treatment approaches for BPDCN include chemotherapy and CD123-targeted tagraxofusp, with allogeneic hematopoietic stem cell transplantation (allo-HCT) considered for eligible patients. The aim of this study is to evaluate the outcomes of allo-HCT based on the data from the BPDCN international registry.
Methods: The BPDCN international registry (ClinicalTrials.gov ID: NCT05430971) was initiated on 1st July, 2022. Data on characteristics, diagnostics, treatment options and treatment responses are collected retrospectively and prospectively from 17 medical centers worldwide. We evaluated baseline characteristics, treatment response, and outcomes of BPDCN patients who underwent allo-HCT.
Results: Of the total 70 patients with BPDCN, 16 underwent allo-HCT. Five of the patients were female. Fifteen of the patients were adults, one patient was 11 years old. The median age was 49 (11-80). In 13 patients (81.25%), the diagnosis was confirmed by bone marrow (BM) examination, other patients were diagnosed by skin biopsy. Splenomegaly was found in 2 patients, 7 patients had lymphadenopathy, one patient had central nervous system (CNS) involvement, and all 16 patients had skin involvement.
Complete blood count (CBC) results were available for 14 patients. 7 patients had normal HGB levels (12-16 g/dL), and 7 patients had anemia. Leukopenia (WBC<4×109/L) was observed in 6 patients, 1 patient had leukocytosis (WBC 67.2×109/L), and seven patients had normal WBC (4-10×109/L). Thrombocytopenia was observed in five patients (PLT<140×109/L).
Immunophenotyping results were as follows: CD123 expression was assessed in 15 patients and was positive in 14 (93%). CD4 was tested in 14 patients, with 12 (86%) showing positivity. CD56 was also assessed in 14 patients and was positive in 12 (86%). Additional markers were evaluated in smaller subsets: CD2AP was assessed in 2 patients and was positive in 1; CD303/BDCA-2 was tested in 2 patients with 1 positive result; and TCL-1 was assessed in 3 patients, showing positivity in 2. Conventional karyotypingwas performed in 8 patients. Cytogenetic abnormalities included one case with 46, XX, der(X)t(X;5) (q28; p13). Another patient demonstrated a complex karyotype involving t(1;16), der(10), t(1;17), del(6), del(12), del(15), and monosomy 17. Molecular analysis was performed in 10 patients (62.5%), and revealed TET2 mutationsin 3 patients, while DNMT3A, CBLC, and EZH2 mutations were identified in 1 and 2 patients, respectively. Initial treatment has utilized ALL-based regimens in 12 patients and included Hyper-CVAD (n=6), cytarabine/idarubicin/VP16 (n=1), ALL-IC BFM 2009 (n=3), GMALL (n=1), EPOCH (n=1). Two patients received venetoclax monotherapy, another 2 were enrolled in SL-401 (tagraxofusp) clinical trial. All patients underwent allo-HCT in first remission except one in SL-401 clinical trial who experienced relapse, the second-line treatment was Hyper-CVAD followed by allo-HCT. Four patients experienced relapse after allo-HCT. Second line therapy was used in all patients, with gemcitabine/oxaliplatin/dexamethasone regimen (n=1), venetoclax/azacytidine (n=1), venetoclax monotherapy (n=1) and SL-401 clinical trial (n=1)․ First two patients experienced stable disease (SD) with duration of 72 and 4 months respectively, the other two were alive at last contact.
As of the last follow- up, 10 (63%) patients were alive with median follow-up of 27 months (range 8-146 months). The follow-up period was calculated from the date of diagnosis up to last contact or death date. Among the cohort, three patients died from causes unrelated to disease progression, two deaths were attributed to disease progression, and one patient was lost to follow-up.
Conclusion: The data confirmed the efficacy of allo-HCT in patients with BPDCN. Our previously reported data highlighted the importance of allo-HCT for the tagraxofusp group, as outcomes were less favorable in those who did not undergo allo-HCT. Based on current evidence, we conclude that optimizing access to tagraxofusp followed by allo-HCT may offer the best potential to improve outcomes in BPDCN.