Plasmacytoid Dendritic Cell Neoplasm Research Articles

Interdigitating Dendritic Cell Sarcoma and Indeterminate Dendritic Cell Tumor: Patient Characteristics, Prognostic Factors, and Survival Outcomes for Rare Dendritic Cell Neoplasms

Background Dendritic cells are nonlymphoid, nonphagocytic, antigen-presenting cells present in lymphoid and nonlymphoid tissue. There are 4 types of dendritic cells: follicular, interdigitating, Langerhans, and fibroblastic cells. The WHO 2022 classification system groups dendritic cell and histiocytic neoplasms into 3 categories: plasmacytoid dendritic cell neoplasms, Langerhans cell and other dendritic cell neoplasms, and histiocytic neoplasms. The 2nd category is subdivided into “Langerhans cells neoplasms” and “other dendritic cell neoplasms”, which contains indeterminate dendritic cell tumor (IDCT) and interdigitating dendritic cell sarcoma (IDCS). The 2022 classification eliminated follicular dendritic cell sarcoma (FDCS) as it is no longer thought to be of hematopoietic origin. A prior Surveillance, Epidemiology, and End Results (SEER) review published in 2013 by Perkins and Shinohara grouped FDCS and IDCS and included 20 cases of IDCS diagnosed between 2001 and 2008. To our knowledge, this is the first update of epidemiologic and survival data for non-Langerhans cell and non-plasmacytoid dendritic cell neoplasms since the WHO reclassification. Methods We used the SEER 22 database, which collects data from cancer registries covering approximately 47.9% of the U.S. population. We selected all patients with cancers falling in the “other dendritic cell neoplasms” category according to the WHO 2022 classification from 2000-2020 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code of 9757/3, which codes for IDCS but also includes IDCT. The Kaplan-Meier method was used to display the survival curves. The Cox proportional hazards model was used to determine p values. Results A total of 72 cases of IDCS/IDCT were identified. Median follow up was 19 months and median OS for the entire cohort was 24 months (95% CI 10-92 months). Of these patients, 61.1% (n=44) were White, 16.7% (n=12) were Hispanic, 13.8% (n=10) were Black, 5.6% (n=4) were Asian or Pacific Islander, and 2 patients were of unknown race. IDCS/IDCT was more common in males than females with a ratio of 1.77. The most common primary sites of involvement were connective tissue in 40.2% (n=29), head and neck in 16.7% (n=12), lymph nodes in 11.1% (n=8), and bone marrow in 8.3% (n=6). Patients with bone marrow involvement had a trend towards worse OS (median OS of 5 months). IDCS/IDCT is more common in adults but does occur in children and adolescents. Only 6 cases were diagnosed in patients under the age of 20 years. Patients who were under the age of 60 years at diagnosis had a median OS of 155 months compared to a median OS of only 10 months for patients who were 60 years or older at diagnosis (Figure 1, p<0.001). Staging was unknown in 12 patients. Of patients with known staging, 56.7% (n=34) had localized disease and 43.3% (n=26) had metastatic disease. Patients with localized disease at diagnosis had a better prognosis with a median OS of 120 months compared to 5 months for patients with metastatic disease at diagnosis (Figure 2, p<0.001). Treatment modality was unknown in 29 of the patients. Of patients with known treatment, 34.9% (n=15) had surgery alone, 20.9% (n=9) had chemo alone, 16.3% (n=7) had radiation alone, and 27.9% (n=12) had combination treatment. Single modality treatment regimens were most popular in patients with localized disease with 48% (n=12) of the patients with known treatment modality getting surgery alone, followed by radiation alone at 24% (n=6).The most common cause of death in this cohort was IDCS/IDCT with 76% of deaths being attributed to the cancer (n=35, there were 46 total deaths). Conclusions Though cases of IDCS and IDCT have more than tripled since 2008, it still remains the rarest type of dendritic cell neoplasm. Connective tissue, head and neck, and lymph nodes were the most common sites involved. Surgical resection was the most common treatment modality followed by chemotherapy. Clinical presentation is rare in patients under the age of 20 years. Age 60 years and older and metastatic disease were associated with poor outcomes with a signal towards worse survival when bone marrow was involved. Our study updates current knowledge of IDCS/IDCT and highlights some of the unknowns in this type of neoplasm, particularly regarding other prognostic factors including treatment effect on survival.

Plasmacytoid dendritic cell neoplasms.

Plasmacytoid dendritic cells (pDCs) are type I interferon-producing cells that modulate immune responses. There are two types of pDC neoplasms: 1) mature pDC proliferation (MPDCP) associated with myeloid neoplasm and 2) blastic pDC neoplasm (BPDCN). MPDCP is a clonal expansion of mature pDCs that is predominantly associated with chronic myelomonocytic leukemia. In contrast, BPDCN is a clinically aggressive myeloid malignancy involving the skin, bone marrow, lymphatic organs, and central nervous system. There are various types of skin lesions, ranging from solitary brown or violaceous to disseminated cutaneous lesions, which often spread throughout the body. The expression of CD4, CD56, CD123, and pDC markers (TCL-1, TCF4, CD303, and CD304, etc.) are typical immunophenotype of BPDCN. Historically, BPDCN treatment has been based on acute leukemia regimens and allogeneic hematopoietic cell transplantation in selected patients. Recent advances in molecular biology and genetics have led to the development of targeted agents, such as tagraxofusp (a recombinant fusion protein targeting CD123), anti-CD123 CAR-T cells, XmAb14045, and IMGN632. Lastly, this review provides a comprehensive overview of pDC neoplasms.

Clofarabine-Based Reduced Intensity Conditioning Regimen with Post-Transplant Cyclophosphamide and Peripheral Stem Cell Graft in Adults with Myeloid Malignancies: Results of the Clo-Baltimore Regimen

Backgound: The Baltimore reduced-intensity conditioning (RIC) regimen using high-dose post-transplant cyclophosphamide (PTCY) is considered as a standard of care for haplo-transplant. However, it is associated with relatively low survivals (OS 46% and EFS 34% at 1 year) and high incidence of relapse (51% at 1 year), especially when considering myeloid malignancies (Luznik, 2008). Here, we have replaced fludarabine by clofarabine, a second-generation purine analogue with high anti-myeloid leukemic activity, as part of the Baltimore regimen (Clo-Baltimore regimen) and we report the results of such an approach in 36 patients with myeloid malignancies.Methods: This retrospective study included 36 adults with a median age of 60.5 (range: 31-70) years who received an allotransplant between March 2014 and March 2017. They were 18 males. Seventeen cases had acute myeloid leukemia (AML), 13 myelodysplastic syndrome (MDS), 3 myelofibrosis (MF), 1 chronic myeloid leukemia (CML), 1 mixed MDS/myeloproliferative syndrome (MPS), and 1 plasmacytoid dendritic cell neoplasm. The status at transplant was as follows: first complete remission (CR) n=16, second CR n=4, third CR n=1, active disease n=15 (MDS n=10, MF n=3; CML n=1, MDS/MPS n=1). Seven patients had already received a first allograft. Twenty-seven patients received a graft from an haploidentical donor (son n=10; daughter n=2; sister n=7; brother n=4; father n=2; nephew n=2) while 8 cases (AML n=1; MDS n=4, myelofibrosis n=2; mixed syndrome n=1) had a matched donor (sibling n=2, mud n=6) and 1 a 9/10 mis-matched unrelated donor. The Clo-Baltimore regimen consisted of Clofarabine 30 mg/m²/day days -6 to -2, cyclophosphamide 14.5 mg/kg day -6, low dose total body irradiation 2 Grays day-1, and PTCY 50 mg/kg/day days +3 and +4. All patients received PBSC as stem cell source at day 0. All patients provided informed consent for data collection before the graft.Results: Except one patient who died during aplasia of multiple organ failure (MOF), all patients engrafted. The median time of neutrophils (>1x109/L) and platelets (>50 x109/L) recoveries were 18 (range: 8-27) and 28.5 (range: 11-111) days, respectively. With a median follow-up of 12.3 months for alive patients (range: 3-39.5), 1-year and 18-month OS were both 74% (0.55-0.86), while 1-year and 18-month DFS were 74% (0.55-0.86) and 62% (0.38-0.78), respectively. At 100 days and 1 year, NRM was 5.5% and 8.3%, respectively. Seven patients have relapsed so far with a median time between graft and relapse of 90 days (range: 66-125). The 1-year relapse incidence was 19.4%. Incidences of grade 2-4 and 3-4 acute GVHD were 48% and 11.4%, respectively, while the incidence of chronic GVHD was 20% (limited 6%, extensive 14%). 1-year and 18-month GRFS were 55% (36-71) and 46% (27-64), respectively. At last follow-up, only 9 patients have died, the causes of death being relapse in 5, dermatomyositis in 1, MOF in 1, sepsis in 1 and grade 4 acute GVHD in 1.In univariate analysis, there were no differences regarding 18-month survivals between patients allografted: 1) in CR vs active disease (OS 65% vs 86%, p=0.13; DFS 56% vs 69%, p=0.18), 2)for AML vs MDS (OS 70% vs 85%, p=0.72; DFS 58% vs 85%, p=0.49), or 3) between haplo-identical vs matched+9/10 mis-matched donors (OS: 69% vs 88%, p=0.29; DFS 59% vs 61%, p=0.57).Conclusion: The Clo-Baltimore regimen has shown very encouraging results in this series for patients with myeloid malignancies, improving OS and DFS at 1 year compared to the Baltimore regimen. A low rate of relapse was observed even although using a RIC regimen, which is suitable for older patients and cases with co-morbidities. An update of the follow up will be provided at the meeting. These data have to be validated prospectively. DisclosuresTouzeau:AbbVie: Research Funding. Moreau:Onyx Pharmaceutical: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria; Takeda: Honoraria; Millennium: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria; Janssen: Consultancy, Honoraria.

Acute mixed lineage leukemia with plasmacytoid dendritic cell neoplasm: report of one case and review of literature

目的 提高对急性混合细胞白血病（MAL）合并母细胞性浆细胞样树突细胞肿瘤（BPDCN）的认识。 方法 通过报道1例MAL合并BPDCN患者并复习相关文献，分析BPDCN的临床特点、治疗方案及预后。 结果 患者为中年女性，临床表现脾大、淋巴结肿大，骨髓涂片可见肿瘤细胞呈母细胞形态，形态单一，核不规则，染色质细，可见数个小核仁，胞质量少，无颗粒状且嗜碱性，骨髓免疫分型可见30.79%的细胞CD56-、CD4-、CD123st+、HLA-DRst+、BDCA2+，为异常浆细胞样树突细胞，根据相关评分系统，表达CD123及BDCA2，总分为3分，可诊断为BPDCN。患者有长期服用硫唑嘌呤以及血小板减少的病史，染色体核型检测发现存在7号染色体缺失，提示该患者有可能存在骨髓增生异常综合征病史，骨髓细胞免疫分型提示同时存在髓系幼稚细胞及异常单核细胞的表达，急性粒-单核细胞白血病诊断明确。 结论 MAL合并BPDCN的诊断需综合临床表现、形态学、免疫学、分子遗传学等，应争取对疾病尽早诊断及治疗。

ABVD療法を施行し，寛解が持続しているblastic plasmacytoid dendritic cell neoplasm

ABVD療法を施行し，寛解が持続しているblastic plasmacytoid dendritic cell neoplasm

Plasmacytoid dendritic cell tumor: A case report.

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.

Therapeutic Effect of Lenalidomide in a Novel Xenograft Mouse Model of Human Blastic NK Cell Lymphoma/Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic natural killer (NK) cell lymphoma/blastic plasmacytoid dendritic cell neoplasm (BNKL) is a rare and aggressive neoplasia characterized by infiltration of blast CD4(+)/CD56(+) cells in the skin, the bone marrow, and peripheral blood. Currently, more efforts are required to better define molecular and biological mechanisms associated with this pathology. To the best of our knowledge, no mouse model recapitulated human BNKL so far. Primary bone marrow cells from a BNKL patient were injected in nonobese diabetes/severe combined immunodeficient interleukin (IL) 2rγ(-/-) mice with the intent to generate the first BNKL orthotopic mouse model. Moreover, because of the lack of efficient treatments for BNKL, we treated mice with lenalidomide, an immunomodulatory and antiangiogenic drug. We generated in mice a fatal disease resembling human BNKL. After lenalidomide treatment, we observed a significant reduction in the number of peripheral blood, bone marrow, and spleen BNKL cells. Tumor reduction parallels with a significant decrease in the number of circulating endothelial and progenitor cells and CD31(+) murine endothelial cells. In mice treated with lenalidomide, BNKL levels of active caspase-3 were significantly augmented, thus showing proapoptotic and cytotoxic effects of this drug in vivo. An opposite result was found for proliferating cell nuclear antigen, a proliferation marker. Our BNKL model might better define the cellular and molecular mechanisms involved in this disease, and lenalidomide might be considered for the future therapy of BNKL patients.