Blastic plasmacytoid dendritic cell neoplasm: a single-center experience

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive hematologic malignancy originating from the precursor of the plasmacytoid dendritic cell. It is very rare and has only recently been recognized as a distinct entity. In this study, we report our experience of BPDCN to review the clinical, pathological features and treatment outcomes. A database at the Asan Medical Center was screened for all patients with BPDCN treated between 2000 and 2010. Seven patients were confirmed as BPDCN and included in this analysis. The median age of the patients was 40 years (range, 18–62 years), and four patients were male. Sites of disease involvement included the skin (n?=?4), lymph node (n?=?4), and peripheral blood/bone marrow (n?=?2). Tumor cells were positive for CD4 (n?=?5), CD56 (n?=?6), and CD123 (n?=?7). Six patients received multi-agent chemotherapy as first-line treatment, while one patient was given radiotherapy. The median progression-free survival was 8.6 months (range, 2.6–28.9 months) and overall survival was 15.1 months (range, 4.4–60.0 months) with a median follow-up period of 13.8 months (range, 1.9–29.9 months). Notably, all four patients with cutaneous involvement survived, whereas those without skin involvement succumbed to death, even though two of them were given salvage chemotherapy. In this study, patients with BPDCN showed various clinical, histological, and immunophenotypical features. Our experience warrants further examination of the prognostic significance of skin involvement in BPDCN.     

Blastic plasmacytoid dendritic cell neoplasm: diagnostic criteria and therapeutical approaches

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare haematological malignancy derived from the precursors of plamacytoid dendritic cells, with an aggressive clinical course and high frequency of cutaneous and bone marrow involvement. Neoplastic cells express CD4, CD43 (also termed SPN), CD45RA and CD56 (also termed NCAM1), as well as the plasmacytoid dendritic cell‐associated antigens CD123 (also termed IL3RA), BDCA‐2 (also termed CD303, CLEC4E) TCL1 and CTLA1 (also termed GZMB). The median survival is only a few months as the tumour exhibits a progressive course despite initial response to chemotherapy. The best modality of treatment remains to be defined. Generally, patients receive acute leukaemia‐like induction, according to acute myeloid leukaemia (AML)‐type or acute lymphoid leukaemia (ALL)‐type regimens. The frequent neuromeningeal involvement indicates systematic pre‐emptive intrathecal chemotherapy in addition to intensive chemotherapy. Allogeneic haematopoietic stem cell transplantation (HSCT), particularly when performed in first remission, may improve the survival. Preliminary data suggest a potential role for immunomodulatory agents and novel targeted drugs. Herein epidemiology, clinical manifestations, diagnosis and management of BPDCN will be presented. In detail, this review focuses on the therapeutic aspects of BPDCN, proposing a treatment algorithm for the management of the disease, including induction chemotherapy, allogeneic HSCT and intrathecal prophylaxis at different steps of treatment, according to compliance, biological and clinical characteristics of patients.     

Blastic plasmacytoid dendritic cell neoplasm: update on therapy especially novel agents

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy mainly affecting elderly patients. Most patients present with asymptomatic skin lesions as the first symptom and has a high frequency of bone marrow involvement. BPDCN is typically characterized by CD4+ and CD 56+ co-expression without common lymphoid or myeloid lineage markers. There is no consensus on the optimal therapeutic strategy for BPDCN. It is highly responsive to chemotherapy but the median event-free survival is very short. Allogeneic stem cell transplantation may improve the prognosis of BPDCN but the rate of relapse is still high. There are no specific targeted agents approved for patients with BPDCN, but advances in the understanding of the pathobiology of BPDCN and the results of early clinical studies have revealed novel targets and potentially effective agents. Novel targeted therapies may improve outcomes for patients with BPDCN in the future.     

母细胞性浆细胞样树突细胞肿瘤二例并文献复习

目的 提高对母细胞性浆细胞样树突细胞肿瘤(blastie plasmacytoid dendritic cell neoplasm,BPDC)的认识.方法 报道2例BPDC患者,并复习文献总结该病临床及实验窒检杏特点,介绍肿瘤细胞起源的最新进展.结果 2例患者均以皮肤结节起病,肿瘤细胞表达CD4和CD56,不表达髓系、T细胞以及B细胞特异性标志.对初始治疗敏感,但迅速复发,病程分别为26、11个月.结论 BPDC是少见的淋巴瘤亚型,具有独特的免疫表型,病程呈侵袭性,预后差.近期研究表明肿瘤细胞起源于浆细胞样树突细胞前体细胞.     

母细胞性浆细胞样树突细胞肿瘤1例及文献复习

目的:通过病例报道及文献复习提高对母细胞性浆细胞样树突细胞肿瘤的临床及病理特征的认识。方法:报道1例母细胞性浆细胞样树突细胞肿瘤患者的临床表现、实验室检查及病理特点,观察CHOP方案疗效,并进行文献复习。结果:CHOP方案化疗对该患者疗效不佳。结论:母细胞性浆细胞样树突细胞肿瘤具有高度侵袭性,预后差,治疗方案尚未统一,尤其高龄患者的有效治疗还有待进一步的研究。     

Blastic plasmacytoid dendritic cell neoplasm in children: diagnostic features and clinical implications

Background

Blastic plasmacytoid dendritic cell neoplasm is a rare malignancy that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited.

Design and Methods

This retrospective study analyzed the pathological and clinical findings of nine cases of blastic plasmactyoid dendritic cell neoplasm presenting in patients under the age of 18 years who were reviewed at our institution. We also identified 20 well-documented additional pediatric cases in the literature.

Results

In the combined analysis, the overall survival rate among the 25 patients with available follow-up, all having received chemotherapy, was 72% (follow-up ranging from 9 months to 13 years, with a median of 30 months). The event-free survival rate was 64%. Nine patients were alive 5 years after the original diagnosis, although only three of them had undergone hematopoietic stem cell transplantation – one in first complete remission and two in second remission. Of the seven patients who lacked cutaneous disease at presentation, 100% survived, including five who were alive more than 5 years after diagnosis, although only two had undergone stem cell transplantation. Among the 18 patients who presented with cutaneous disease and for whom follow-up data were available, only 11 survived (61%). Detailed immunophenotypic characterization and clinical features of all cases are presented. Unexpectedly, three of four cases of blastic plasmacytoid dendritic cell neoplasm tested showed focal positivity for S-100. S-100 was negative in 28 cases of acute myeloid leukemia evaluated for this marker.

Conclusions

In contrast to adult cases, in which long-term survival depends on stem cell transplantation in first complete remission, blastic plasmacytoid dendritic cell neoplasms in children are clinically less aggressive. Treatment with high-risk acute lymphoblastic leukemia-type chemotherapy appears to be effective, and stem cell transplantation may be reserved for children who relapse and achieve a second remission. Outcomes were more favorable in cases that lacked cutaneous disease at presentation, although a comparison of cutaneous and non-cutaneous cases might be confounded by differences in treatment regimens. Focal expression of S-100 may be seen in concert with other markers of plasmacytoid dendritic cells.     

Blastic plasmacytoid dendritic cell neoplasm without cutaneous lesion at presentation: case report and literature review

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and highly aggressive hematological malignancy derived from precursors of plasmacytoid dendritic cells. This disease typically presents with cutaneous involvement as the first manifestation, with subsequent or simultaneous spread to bone marrow and peripheral blood. It is exceedingly rare to diagnose BPDCN without a cutaneous lesion. Here, we report a 21-year-old male who was diagnosed with BPDCN in the absence of cutaneous symptoms. Clinically, left inguinal nodules were noticed for 4 months. The diagnosis of BPDCN was established based on histological and immunohistochemical study of a lymph node biopsy. The patient was classified as stage IVA with bone marrow involvement and underwent three cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine. A complete response was established after one cycle; however, the patient relapsed with disseminated cutaneous lesions and bone marrow involvement following a response duration of 10 months. This case is significant for BPDCN presenting with lymph node and bone marrow involvement in the absence of characteristic cutaneous manifestations.     

Blastic plasmacytoid dendritic cell neoplasm: the first report of two cases treated by 5‐Azacytidine

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy which was first included as an independent cutaneous lymphoma in the 2008 World Health Organisation (WHO) classification (1). BPDCN usually has an extremely poor prognosis, with quick relapses after chemotherapy (2; 3). Here, we report two cases of patients diagnosed in 2011 with BPDCN and myelodysplasia, and who were treated for the first time with 5‐azacytidine (5‐Aza); a drug approved by the Food and Drug Administration (FDA) and mainly used in the treatment of myelodysplastic syndrome (Kaminskas E, et al. 2005 Clin Cancer Res, 11, 3604–8). The first case was an 81‐year‐old man who presented with unusual CD10+, CD56‐ immunohistochemistry and 45X, ‐Y abnormality using fluorescent in situ hybridization (FISH) analysis. The second case was a 78‐year‐old woman who manifested monosomy 13 and chromosome instability due to D13S319 locus deletion in 13q14 as determined by FISH. Both patients showed excellent responses of their skin lesions after one cycle of chemotherapy, and their hematological disease was stabilized; however, pulmonary sepsis set in, followed by neutropenia after the fourth and the fifth cycle of treatment, that is, eight and 9 months postdiagnosis, respectively, leading to patient death.     

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10‐Color flow cytometry diagnosis and HyperCVAD therapy

Few studies describe the comprehensive immunophenotypic pattern of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the bone marrow and its treatment. This retrospective analysis evaluates the diagnostic flow cytometry (FCM) pattern and outcome of nine patients diagnosed with BPDCN. A four‐tube 10‐color FCM panel used for diagnosis of acute leukemia (AL), showed cells in the blast gate (CD45dim/low SSC) and were positive for CD4(bright), CD33(dim), CD56(heterogenous), CD123(bright), CD36, CD38, HLA‐DR, CD71. Seven patients received front‐line induction therapy with HyperCVAD with an overall response rate of 86%. Five of six responders underwent planned allogeneic hematopoietic cell transplantation (allo‐HCT). For a median follow up of 13.3 months, the 1‐year disease free survival and overall survival were 56 and 67%, respectively. An accurate diagnosis of BPDCN can be made by 10‐color FCM using a four‐tube AL panel demonstrating a characteristic pattern of antigen expression. Front‐line induction chemotherapy with HyperCVAD can yield high remission rates, but allo‐HCT is required for long‐term durable remissions. Am. J. Hematol. 91:283–286, 2016. © 2015 Wiley Periodicals, Inc.     

Blastic plasmacytoid dendritic cell neoplasm should be treated with acute leukemia type induction chemotherapy and allogeneic stem cell transplantation in first remission

Blastic plasmacytoid dendritic cell (BPDC) neoplasm is a rare but clinically aggressive tumor known to be derived from the precursors of plasmacytoid dendritic cells (CD123+) with a high frequency of cutaneous and bone marrow involvement. Though majority of the patients initially respond to multi-agent chemotherapy, most would relapse within a year. We hereby report a patient with disseminated cutaneous BPDC with marrow involvement diagnosed by typical histo-pathological and flow-cytometric findings. He was subsequently treated with leukemia type induction regimen followed by allogeneic stem cell transplantation in first complete remission. He is now 18 months posttransplantation with continued remission with full donor chimerism. We recognize that BPDC with marrow involvement behaves like acute myeloid leukemia and aggressive treatment followed by stem cell transplantation may lead to long-term remission in selected cases.