CD4+ CD56+ hematodermic/plasmacytoid dendritic cell tumor with response to pralatrexate

Leitenberger, Justin J.; Berthelot, Cindy; Polder, Kristel D.; Pro, Barbara; McLaughlin, Peter; Jones, Dan; Duvic, Madeleine

doi:10.1016/j.jaad.2007.12.012

Cited by 41 publications

(23 citation statements)

References 20 publications

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“…52 Most recently, 2 studies have shown utility of the hypomethylating agent azacitidine in BPDCN. Overlap with MDS, conversion to AML in a percentage of BPDCN patients, and recognition of novel mutations in DNA methylation genes (eg, TET2), all lend credibility to the use of epigenetic modification in BPDCN patients.…”

Section: Treatment Of Elderly Infirm or Transplant-ineligible Patientsmentioning

confidence: 99%

Treatment of blastic plasmacytoid dendritic cell neoplasm

Sullivan

Rizzieri

2016

Hematology

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Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare myeloid malignancy with no defined standard of care. BPDCN presents most commonly with skin lesions with or without extramedullary organ involvement before leukemic dissemination. As a result of its clinical ambiguity, differentiating BPDCN from benign skin lesions or those of acute myeloid leukemia with leukemia cutis is challenging. BPDCN is most easily defined by the phenotype CD4 1 CD56 1 CD1231 lineage -MPO -, although many patients will present with variable expression of CD4, CD56, or alternate plasmacytoid markers, which compounds the difficulty in differentiating BPDCN from other myeloid or lymphoid malignancies. Chromosomal aberrations are frequent, and the mutational landscape of BPDCN is being rapidly characterized although no obvious molecular target for chemoimmunotherapy has been identified. Chemotherapy regimens developed for acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome have all been used to treat BPDCN. Relapse is frequent, and overall survival is quite poor. Allogeneic transplantation offers a chance at prolonged remission and possible cure for those who are eligible; unfortunately, relapse remains high ranging from 30% to 40%. Novel therapies such as SL-401, a diphtheria toxin conjugated to interleukin-3 (IL-3) is commonly overexpressed in BPDCN and other aggressive myeloid malignancies and has shown considerable promise in ongoing clinical trials. Future work with SL-401 will define its place in treating relapsed or refractory disease as well as its role as a first-line therapy or bridge to transplantation. Learning Objectives• To understand the clinical and laboratory approach for differentiating BPDCN from acute myeloid leukemia with cutaneous manifestations • To consider appropriate first-line and salvage treatments for BPDCN, including the utility of hematopoietic allogeneic stem cell transplantation and novel agents in various patient populations

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Section: Treatment Of Elderly Infirm or Transplant-ineligible Patientsmentioning

confidence: 99%

Treatment of blastic plasmacytoid dendritic cell neoplasm

Sullivan

Rizzieri

2016

Hematology

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“…22 IL-3 has also been shown to be a critical survival factor for plasmacytoid dendritic cells. 33 Thus, interference of this pathway by SL-401 may explain the high sensitivity of BPDCN compared with the sensitivity of other myeloid and lymphoid leukemic cells.There is still no consensus on the best therapeutic approach for BPDCN, 3,[12][13][14][15][34][35][36][37][38] and, overall, BPDCN remains a chemotherapy-resistant disease and may also resist the graft-versus-leukemia effect, since 32% of patients relapse after allogeneic hematopoietic cell transplantation according to a recent study. 13 Thus, targeted or immune-based therapies are alternative strategies to treat this aggressive leukemia.…”

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confidence: 99%

In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent

Angelot‐Delettre¹,

Roggy²,

Frankel³

et al. 2014

Haematologica

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ABSTRACTlabile group of amino acids to a diphtheria toxin (DT) payload that has been truncated at its receptor binding region. 20 Since IL-3, the natural ligand for IL-3R, binds with very high specificity and avidity, 21 SL-401 is able to transport DT efficiently and preferentially to cells that overexpress IL-3R, leading to internalization followed by receptor-mediated endocytosis and localization of SL-401 to early endosomes. After cleavage of the SL-401 DT constituent in the acidic medium of endosomes, DT translocates into the cytosol and binds to ADP-ribosylated elongation factor 2, leading to blockade of protein synthesis and cell death. 22 Given the ubiquitous and high expression of IL-3R by BPDCN and the lack of therapies available to treat BPDCN, SL-401 is a potential therapeutic for BPDCN. The present study evaluated the cytotoxicity of SL-401 against patient-derived BPDCN cell lines (CAL-1 and GEN2.2) and primary BPDCN cells isolated directly from 12 patients. The investigations were performed in vitro, as well as in vivo in a murine model of BPDCN. The aim of the study was to provide further support for the use of SL-401 in patients suffering from BPDCN. Methods Patients' cells and cell linesPeripheral blood or bone marrow cells were obtained for diagnostic purposes from 12 BPDCN patients (Table 1) from our national network that collects data and cells from cases diagnosed in France since (authorization number #DC-2008. BPDCN was diagnosed from the results of histopathology and immunostaining of cutaneous lesions, blood or bone marrow. 2,8 Two established cell lines derived from BPDCN patients were used (GEN 2.2, patent #0215927, Dr. Plumas, EFS Rhone-Alpes, Grenoble, France and CAL-1, Dr. Maeda, Nagasaki University, Japan) as well as TF/H-Ras (Prof. Frankel) and CD123 neg (MFI<800) Daudi cell lines (ACC78, DSMZ Braunschweig, Germany) as positive and negative controls, respectively. Other lymphoid and myeloid leukemic cells used to compare sensitivity to SL-401 are described in the Online Supplementary Appendix. Drug and cultureThe SL-401 drug (Stemline Therapeutics, New York, NY, USA) was stored at -80°C and tested at eight concentrations ranging from 365 pM to 0.08 fM (21 ng/mL to 0.4 ng/mL) in order to cover (including myeloperoxidase, CD13, CD33, CD117, CD15, CD65, CD14, CD64); T : T lymphoid markers (including membrane CD3, intracytoplasmic CD3, CD7, CD5, CD2, CD8) Cytotoxicity evaluation by flow cytometryFlow cytometry was performed using a CANTO II cytometer (BD Biosciences, San Jose, CA, USA) and DIVA 6.2 software (BD Biosciences). The cytotoxic effects of SL-401 and the various drugs were evaluated using annexin-V and 7-amino actinomycin D (AV/7AAD) and a panel of different monoclonal antibodies to gate the blastic population described in the Online Supplementary Appendix. In the mouse model, anti-mouse and anti-human CD45 plus anti-human CD123, CD4, CD56, CD304 were used to identify BPDCN human cells (Online Supplementary Appendix). A defined number of calibrated 3-mm latex beads (Flowco...

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“…Most patients also have extracutaneous manifestations at presentation [1,4,5,10]. Plasmacytoid dendritic cell tumors were formerly categorized as blastic NK-cell lymphoma because of CD56 expression [1][2][3]6,7,11,13]. Moreover, CD4 expression is positive, but CD2, CD3, and CD7 expression is usually negative.…”

Section: Discussionmentioning

confidence: 99%

“…Anthracycline-based chemotherapies, such as the CHOP and hyper-CVAD regimens, may be effective, whereas high-dose chemotherapy and autologous stem cell transplantation may be appropriate in some selected cases [3,5,[8][9][10][11]13]. The presented patient received the CHOP chemotherapy regimen, and after the first course the patient's skin lesions regressed and lymphadenopathy disappeared.…”

Section: Discussionmentioning

confidence: 99%

“…According to the WHO 2008 classification of lymphoid malignancies, plasmacytoid dendritic cell tumor-a rare non-Hodgkin's lymphoma (NHL)-was formerly defined as blastic NK-cell lymphoma in the WHO 2001 classification and as CD4+/CD56+ hematodermic neoplasm in the European Organization of Research and Treatment of Cancer 2005 classification of cutaneous lymphoma [1][2][3][4][5][6][7][8][9][10]. Plasmacytoid dendritic cell tumors generally occur in middle-aged and elderly men; the skin is usually the first site of presentation in 90% of patients [1,4].…”

Section: Introductionmentioning

confidence: 99%

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Plasmacytoid dendritic cell tumor: A case report

Döger

Çetin

Hekımgıl³

et al. 2011

Turk J Hematol

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A 62-year-old man presented with a painless eruption on his arms and trunk. Physical examination showed 2 well-demarcated erythematous plaques on the anterior trunk and 6 purple-red papules on the back and upper extremities. Blood chemistry and computed tomography results were normal. Herein we describe a patient with plasmacytoid dendritic cell neoplasm in the absence of systemic symptoms. (Turk J Hematol 2011; 28: 312-6) Key words: Cutaneous lymphoma, NK-cell lymphoma, hematodermic lymphoma, plasmacytoid dendritic cell neoplasm Received: May 13, 2009 Accepted: April 30, 2010 Özet Altmış iki yaşında erkek hasta gövdesinde ve kollarındaki ağrısız erupsiyon şikayetleri ile başvurdu. Fizik muyane de gövdesinin ön kısmında iyi sınırlı eritamatous plak, üst ekstremite ve sırtında mor kırmızı papuller saptandı. Kan biyokimyası ve tomografisi olağandı. Burada, sistemik bulgusu olmayan plasmasitoid dendritik hücreli neoplasmı olan bir hastayı sunduk (Turk J Hematol 2011; 28: 312-6)

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CD4+ CD56+ hematodermic/plasmacytoid dendritic cell tumor with response to pralatrexate

Cited by 41 publications

References 20 publications

Treatment of blastic plasmacytoid dendritic cell neoplasm

Treatment of blastic plasmacytoid dendritic cell neoplasm

In vivo and in vitro sensitivity of blastic plasmacytoid dendritic cell neoplasm to SL-401, an interleukin-3 receptor targeted biologic agent

Plasmacytoid dendritic cell tumor: A case report

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