Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematologic malignancy that can involve the skin, bone marrow, lymph nodes and central nervous system (CNS). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an important consolidative option for eligible patients who achieve remission. For patients with relapsed or refractory disease who lack a suitable donor, however, durable disease control remains particularly challenging.
A team from the Lymphoma and Myeloma dept. at GoBroad Healthcare Group, has reported a case in Frontiers in Immunology describing an integrated treatment strategy combining high-dose conditioning, autologous stem cell transplantation (ASCT), anti-CD123 CAR-T therapy and venetoclax maintenance.
Fan Yang and colleagues conducted the study, with Kai Hu serving as corresponding author.
Persistent MRD in the Absence of a Suitable Donor
The patient was a 55-year-old man who presented with generalized lymphadenopathy and diffuse violaceous skin plaques involving the neck and upper arms. Pathologic and immunophenotypic findings supported a diagnosis of BPDCN. Bone marrow examination showed 26% BPDCN blasts, while cerebrospinal fluid flow cytometry confirmed CNS involvement.
Following alternating Hyper-CVAD therapy with intrathecal treatment, the patient achieved complete remission and CNS clearance after nine cycles. Bone marrow minimal residual disease (MRD), however, remained detectable at 0.98%.
As no suitable HLA-matched allogeneic donor was available, the treating team developed an individualized strategy aimed at achieving deeper molecular disease clearance while providing hematopoietic support.
ASCT Followed by Anti-CD123 CAR-T Achieved MRD-Negative Remission
After high-dose conditioning, autologous stem cells were infused on Day 0, followed by anti-CD123 CAR-T cells on Day +2.
CAR-T cells expanded rapidly in peripheral blood and reached peak levels on Day +14. Bone marrow flow cytometry showed no detectable MRD on Days +18 and +25. By Day +90, the patient had achieved complete hematologic recovery, with continued MRD negativity in both the bone marrow and cerebrospinal fluid.
The course was complicated by Grade 3 cytokine release syndrome (CRS) and suspected immune effector cell-associated HLH-like syndrome (IEC-HS). These inflammatory toxicities were managed with glucocorticoids and emapalumab, an antibody targeting interferon-γ.
Persistent thrombocytopenia also occurred. The team subsequently performed lymphodepletion followed by a second “rescue” autologous stem cell infusion. Platelet engraftment was achieved by Day +58. In the published report, the investigators describe autologous stem cell support as a potential hematopoietic rescue strategy for prolonged CAR-T-associated cytopenia.
Venetoclax Maintenance and More Than 13 Months of Disease-Free Survival
Because BPDCN is associated with a substantial risk of relapse and the patient's tumor showed strong BCL-2 expression, venetoclax maintenance at 50 mg/day was initiated three months after transplantation.
At the time of publication, the patient remained in sustained MRD-negative complete remission, with disease-free survival exceeding 13 months.
The case integrates intensive disease control, targeted cellular immunotherapy, hematopoietic rescue and molecular maintenance within a single treatment pathway. For patients with relapsed/refractory BPDCN who are unable to undergo allo-HSCT, the approach may represent a potential management option worthy of further investigation.
The study also highlights an important challenge of targeting CD123. Although CD123 is highly expressed in BPDCN, it can also be found on normal hematopoietic stem and progenitor cells, raising the risk of prolonged myelosuppression and cytopenia. Balancing antitumor activity with hematopoietic safety will therefore remain a key consideration in the continued development of CD123-directed cellular therapies.
The authors further emphasize the importance of monitoring inflammatory complications beyond conventional CRS, including IEC-HS, and tailoring toxicity management to each patient's clinical course.
As this report describes a single patient, the results should not be interpreted as establishing a new standard of care. Larger clinical studies and longer follow-up will be required to determine the safety, durability and broader applicability of combining ASCT, anti-CD123 CAR-T therapy and venetoclax maintenance.
GoBroad continues to explore individualized CAR-T strategies and integrated treatment approaches for patients with high-risk and relapsed/refractory hematologic malignancies. The combination of clinical assessment with pathology, molecular diagnostics, imaging and longitudinal disease monitoring—including MRD and ctDNA—may help identify patients most likely to benefit from precision cellular therapies and enable earlier detection of relapse.
Publication:
Yang F, Li D, Lei Y, et al. Anti-CD123 CAR-T therapy combined with autologous SCT and venetoclax maintenance in refractory BPDCN ineligible for allogeneic transplantation: a case report and review of the literature. Frontiers in Immunology. 2026;17:1922400.
DOI: 10.3389/fimmu.2026.1922400
