Treatment Approaches for Non–Transplant Eligible Patients With BPDCN

Summary for Physicians: Clinical Considerations in BPDCN Management

Case Highlights:

• The combination of skin lesions, cytopenias, and circulating blasts raised early suspicion for BPDCN.

• Immunophenotyping confirmed the diagnosis with hallmark markers (CD4+, CD56+, CD123+, CD303+, TCL1+).

• CNS involvement at diagnosis (12% cerebral spinal fluid [CSF] blasts) was a key finding, indicating high-risk disease.

Treatment Selection Factors:

• Patient specific: Age, performance status (ECOG 1), and absence of major comorbidities beyond stable cardiac history supported the use of tagraxofusp.

• Non–patient specific: CNS involvement, disease burden, and access to CNS-penetrating agents also influenced initial therapy choice.

CNS Involvement Considerations:

• CNS disease necessitates integrated systemic and intrathecal (IT) therapy from the start.

• Tagraxofusp alone does not penetrate the CNS effectively, reinforcing the need for concurrent IT prophylaxis or treatment.

Intrathecal (IT) Chemotherapy Approach:

• Begin IT therapy promptly alongside systemic treatment.

• Standard regimen: IT methotrexate ± cytarabine and hydrocortisone, administered weekly until CSF clearance, then spaced as prophylaxis.

• Monitor CSF cytology and flow cytometry regularly to assess response and guide tapering.

This case illustrates the critical need for early CNS evaluation and a multidisciplinary strategy in BPDCN, tailoring therapy based on disease characteristics and patient fitness.