Azacitidine in the treatment of blastic plasmacytoid dendritic cell neoplasm: a report of 3 cases

Khwaja, Raida; Daly, Andrew; Wong, Michael K.; Mahé, Etienne; Cerquozzi, Sonia

doi:10.3109/10428194.2016.1160084

Cited by 32 publications

(25 citation statements)

References 13 publications

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“…A recent study by our group strongly supports the use of hypomethylating agents, demonstrating a significant enrichment in epigenetic modifiers mutations in the setting of BPDCN [22]. In line with our preclinical findings, two clinical reports have demonstrated activity of 5-azacitidine in BPDCN, although the responses were generally transient once again [104,105]. Combinatory approaches based on hypomethylating agents should be explored in the near future.…”

Section: Therapy Of Blastic Plasmacytoid Dendritic Neoplasmsupporting

confidence: 84%

Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects

Sapienza

Pileri

Derenzini

et al. 2019

Cancers

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare tumour, which usually affects elderly males and presents in the skin with frequent involvement of the bone-marrow, peripheral blood and lymph nodes. It has a dismal prognosis, with most patients dying within one year when treated by conventional chemotherapies. The diagnosis is challenging, since neoplastic cells can resemble lymphoblasts or small immunoblasts, and require the use of a large panel of antibodies, including those against CD4, CD56, CD123, CD303, TCL1, and TCF4. The morphologic and in part phenotypic ambiguity explains the uncertainties as to the histogenesis of the neoplasm that led to the use of various denominations. Recently, a series of molecular studies based on karyotyping, gene expression profiling, and next generation sequencing, have largely unveiled the pathobiology of the tumour and proposed the potentially beneficial use of new drugs. The latter include SL-401, anti-CD123 immunotherapies, venetoclax, BET-inhibitors, and demethylating agents. The epidemiologic, clinical, diagnostic, molecular, and therapeutic features of BPDCN are thoroughly revised in order to contribute to an up-to-date approach to this tumour that has remained an orphan disease for too long.

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Section: Therapy Of Blastic Plasmacytoid Dendritic Neoplasmsupporting

confidence: 84%

Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects

Sapienza

Pileri

Derenzini

et al. 2019

Cancers

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“…In the past, two reports experimented the use of 5’-azacytidine in elderly BPDCN patients, though this therapeutic choice was not yet sustained by a molecular rationale. 47,48 Here we demonstrate that 5’-azacytidine is more effective in tumor eradication when combined with decitabine. Further studies are ongoing to elucidate the synergistic mechanisms between the two drugs.…”

Section: Discussionmentioning

confidence: 61%

Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target

et al. 2018

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy for which there is still no effective therapy. In order to identify genetic alterations useful for a new treatment design, we used whole-exome sequencing to analyze 14 BPDCN patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program to be the most significantly undermined ( P <0.0001). In particular, twenty-five epigenetic modifiers were found mutated (e.g. ASXL1, TET2, SUZ12, ARID1A, PHF2, CHD8); ASXL1 was the most frequently affected (28.6% of cases). To evaluate the impact of the identified epigenetic mutations at the gene-expression and Histone H3 lysine 27 trimethylation/acetylation levels, we performed additional RNA and pathology tissue-chromatin immunoprecipitation sequencing experiments. The patients displayed enrichment in gene signatures regulated by methylation and modifiable by decitabine administration, shared common H3K27-acetylated regions, and had a set of cell-cycle genes aberrantly up-regulated and marked by promoter acetylation. Collectively, the integration of sequencing data showed the potential of a therapy based on epigenetic agents. Through the adoption of a preclinical BPDCN mouse model, established by CAL-1 cell line xenografting, we demonstrated the efficacy of the combination of the epigenetic drugs 5’-azacytidine and decitabine in controlling disease progression in vivo .

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“…A single case report described a reasonable remission (1 year) and tolerability of oral etoposide in an older patient with relapsed BPDCN and another described partial disease control of cutaneous lesions with weekly infusions of prala-trexate 48,49. A case series supporting the use of azacytidine has also been reported as has the use of repeat courses of donor lymphocyte infusions after allogeneic HSCT relapse 50,51…”

Section: Treatmentmentioning

confidence: 99%

Blastic plasmacytoid dendritic cell neoplasm: challenges and future prospects

Trottier

Cerquozzi

2017

BLCTT

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare CD4+ CD56+ myeloid malignancy that is challenging to diagnose and treat. BPDCN typically presents with nonspecific cutaneous lesions with or without extra-cutaneous manifestations before progressing to leukemia. Currently, there is no standard of care for the treatment of BPDCN and various approaches have been used including acute myeloid leukemia, acute lymphoblastic leukemia, and lymphoma-based regimens with or without stem cell transplantation. Despite these treatment approaches, the prognosis of BPDCN remains poor and there is a lack of prospective data upon which to base treatment decisions. Recent work examining the mutational landscape and gene expression profiles of BPDCN has identified a number of potential therapeutic targets. One such target is CD123, the α subunit of the human interleukin-3 receptor, which is the subject of intervention studies using the novel agent SL-401. Other investigational therapies include UCART123, T-cell immunotherapy, and venetoclax. Prospective trials are needed to determine the best treatment for this uncommon and aggressive neoplasm.

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Azacitidine in the treatment of blastic plasmacytoid dendritic cell neoplasm: a report of 3 cases

Cited by 32 publications

References 13 publications

Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects

Blastic Plasmacytoid Dendritic Cell Neoplasm: State of the Art and Prospects

Blastic plasmacytoid dendritic cell neoplasm: genomics mark epigenetic dysregulation as a primary therapeutic target

Blastic plasmacytoid dendritic cell neoplasm: challenges and future prospects

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