Allogeneic hematopoietic cell transplantation for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Bashir, Qaiser; Milton, Denái R.; Popat, Uday; Kebriaei, Partow; Hosing, Chitra; Khouri, Issa F.; Rezvani, Katayoun; Nieto, Yago; Oran, Betül; Srour, Samer A.; Saini, Neeraj; Olson, Amanda; Alatrash, Gheath; Rondón, Gabriela; Konopleva, Marina; Champlin, Richard E.; Shpall, Elizabeth J.; Qazilbash, Muzaffar H.; Pemmaraju, Naveen

doi:10.1038/s41409-021-01478-5

Cited by 29 publications

(18 citation statements)

References 23 publications

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“…Sapienza et al [ 14 ] performed whole-exome sequencing and RNA sequencing on 14 BPDCN cases, identified deregulation of the epigenetic program as a genetic hallmark of BPDCN, and suggested a novel therapeutic approach based on the combination of two hypomethylating agents, 5′-azicytidine and decitabine. Stem cell transplantation has been shown to result in durable remissions [ 38 , 39 ]. Our studies also showed that stem cell transplantation significantly prolonged the overall survival of patients with BPDCN.…”

Section: Discussionmentioning

confidence: 99%

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Yin

Pemmaraju

You

et al. 2021

Cancers

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm derived from plasmacytoid dendritic cells. While advances in understanding the pathophysiology of the disease have been made, integrated systematic analyses of the spectrum of immunophenotypic and molecular alterations in real-world clinical cases remain limited. We performed mutation profiling of 50 BPDCN cases and assessed our findings in the context of disease immunophenotype, cytogenetics, and clinical characteristics. Patients included 42 men and 8 women, with a median age of 68 years (range, 14–84) at diagnosis. Forty-two (84%) patients had at least one mutation, and 23 (46%) patients had ≥3 mutations. The most common mutations involved TET2 and ASXL1, detected in 28 (56%) and 23 (46%) patients, respectively. Co-existing TET2 and ASXL1 mutations were present in 17 (34%) patients. Other recurrent mutations included ZRSR2 (16%), ETV6 (13%), DNMT3A (10%), NRAS (10%), IKZF1 (9%), SRSF2 (9%), IDH2 (8%), JAK2 (6%), KRAS (4%), NOTCH1 (4%), and TP53 (4%). We also identified mutations that have not been reported previously, including ETNK1, HNRNPK, HRAS, KDM6A, RAD21, SF3A1, and SH2B3. All patients received chemotherapy, and 20 patients additionally received stem cell transplantation. With a median follow-up of 10.5 months (range, 1–71), 21 patients achieved complete remission, 4 had persistent disease, and 24 died. Patients younger than 65 years had longer overall survival compared to those who were ≥65 years (p = 0.0022). Patients who had ≥3 mutations or mutations in the DNA methylation pathway genes had shorter overall survival (p = 0.0119 and p = 0.0126, respectively). Stem cell transplantation significantly prolonged overall survival regardless of mutation status. In conclusion, the majority of patients with BPDCN have somatic mutations involving epigenetic regulators and RNA splicing factors, in addition to ETV6 and IKZF1, which are also frequently mutated. Older age, multiple mutations, and mutations in the DNA methylation pathway are poor prognostic factors.

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Section: Discussionmentioning

confidence: 99%

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Yin

Pemmaraju

You

et al. 2021

Cancers

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“…13 The ability to achieve sustained complete remission after HSCT is predicated on the ability of patients to withstand myeloablative treatment. 14 For some older patients, reduced-intensity conditioning using fludarabine-containing modalities or low-dose dexamethasone, VP16, ifosfamide, and carboplatin have been used for this reason before allo-transplantation. 15,16 Although induction chemotherapy followed by HSCT became widely adopted in the management of BPDCN and was shown to provide durable disease control in selected fit patients, the effect on disease-free survival was only marginal compared with the effect of chemotherapy alone.…”

Section: Conventional Chemotherapeutic Agentsmentioning

confidence: 99%

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics

Adimora

Wilson

Pemmaraju

2022

Cancer

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy arising from precursor dendritic cells. BPDCN cells characteristically express several markers on their cell surfaces including CD123, CD4, and CD56. Because of its rarity and challenging clinical presentation, there was no standard of care in managing BPDCN for decades and its prognosis overall was poor. However, as understanding of this rare neoplasm has increased, so have treatment options. The conventional cytotoxic chemotherapy regimens once used in the treatment of BPDCN were modest in their impact on disease relapse until paired with hematopoietic stem cell transplant. Although recent data suggest that there still remains a role for chemotherapeutic agents, targeted modalities have expanded the overall BPDCN treatment landscape. The CD123-targeted agent, tagraxofusp, was the first Food and Drug Administration-approved monotherapy in the treatment of BPDCN. Since its inception, several CD123-targeted and other cell-surface agents have been investigated, with many agents still in the preclinical stages. Although relapsed/refractory disease and central nervous system disease both remain formidable areas of research, there are several promising therapeutic approaches that could have a significant impact on the trajectory of treatment. This review will provide detailed insight on the novel drugs currently in use and those being explored in the management of BPDCN.

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“…Among responders in each of the frontline treatment groups, a common significant variable was the ability to undergo HSCT, especially in CR1, which, regardless of frontline treatment regimen selected, remains a very important part of a curative approach in BPDCN, especially for younger/fit patients. 51 Despite no improvement in median OS compared with other treatment regimens, the ability to yield a higher CR rate with low rates of adverse events suggests that HCVAD retains an important role in the frontline treatment of BPDCN. As above, HCVAD represents the optimal combination of vinca alkaloid, glucocorticoid, anthracycline, and combination chemotherapy, in addition to intrathecal chemotherapy, as an intensive and efficacious frontline regimen for BPDCN.…”

Section: Discussionmentioning

confidence: 98%

“…This may be due to the heterogenous group of patients with varying degrees of disease involvement, and of subsequent lines of therapy. Among responders in each of the frontline treatment group, a common significant variable was the ability to undergo HSCT, especially in CR1, which, regardless of frontline treatment regimen selected, clearly remains a very important part of a curative approach in BPDCN, especially for younger/fit patients 51 . Despite no improvement in median OS compared to other treatment regimens, the ability to yield a higher rate of CR with low rates of adverse events suggests that HCVAD remains an important role in the frontline treatment of BPDCN.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD

et al. 2022

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive blood cancer, often involving skin, bone marrow, lymph nodes, as well as central nervous system (CNS) involvement in 20-30% of patients. Despite significant progress in CD123- and BCL-2-targeted therapy, most patients are not cured outside of hematopoietic stem cell transplant (HSCT), and CNS relapses are being observed quite frequently. Combination approaches with both targeted and chemotherapy agents plus incorporation of prophylactic CNS-directed therapy are urgently needed. In this setting, we sought to analyze outcomes of the cytotoxic chemotherapy backbone regimen hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (HCVAD) in BPDCN. We conducted a retrospective analysis of patients with BPDCN (n=100), evaluating complete remission (CR) and median overall survival (OS) among three groups: those who received frontline HCVAD-based (n=35) vs SL-401 (n=37) vs other regimens (n=28). HCVAD-based regimens yielded higher CR (80% vs 59% vs 43%, p=0.01). There was no significant difference in OS (28.3 vs 13.7 vs 22.8 months p=0.41), nor significant difference in remission duration probability among treatment groups (38.6 vs NR vs 10.2 months; p=0.24). HSCT was performed in 51% vs 49% vs 38% respectively (p=0.455). These results suggest a continued important role for HCVAD-based chemotherapy for BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting. Further studies must establish the clinical activity, feasibility, and safety, of doublet/triplet combinations of targeted therapies plus cytotoxic agents and addition of CNS prophylaxis, with ultimate goal of durable long-term remissions for patients with BPDCN.

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Allogeneic hematopoietic cell transplantation for patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Cited by 29 publications

References 23 publications

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN): A promising future in the era of targeted therapeutics

Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD

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