Fast Facts: Blastic Plasmacytoid Dendritic Cell Neoplasm

F. Garnache Ottou, N. Pemmaraju, A.A. Lane, E. Deconinck

Description

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare fast-growing hematodermic neoplasm that most often occurs in older men. It is notable for its highly aggressive behavior, with cutaneous, lymph node and bone marrow involvement. In the past, BPDCN has been poorly understood, recognized and treated, and consequently has had a poor prognosis. Today, it has been reclassified as a myeloid neoplasm and there is greater understanding of the disease’s clinical features, course and pathology, a new diagnostic test that makes prompt diagnosis possible and a new targeted therapy that, so far, has been shown to at least double survival. The complexity of caring for patients with BPDCN stems from both its rarity and its multiorgan involvement. 'Fast Facts: Blastic Plasmacytoid Dendritic Cell Neoplasm' is designed to bring hematologists, oncologists, dermatologists, pathologists, clinical nurse specialists and trainees in all these fields up to speed on the latest developments, as well as providing the most up-to-date information on first-line chemotherapy, consolidation treatments and stem cell transplantation. It will aid readers of all relevant medical disciplines to implement prompt diagnosis and effective management. Table of Contents: • What is BPDCN? Diagnosis • Management • Unmet needs and future directions

Informations

• Publié par: S. Karger AG
• Date de parution: 12 février 2021
• Nombre de lectures: 0
• EAN13: 9783318068078
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Fast Facts: Blastic Plasmacytoid Dendritic Cell Neoplasm First published 2021
Text 2021 Eric Deconinck, Andrew A Lane, Naveen Pemmaraju, Francine Garnache Ottou
2021 in this edition S. Karger Publishers Ltd
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ISBN 978-3-318-06806-1
Deconinck E (Eric) Fast Facts: Blastic Plasmacytoid Dendritic Cell Neoplasm/ Eric Deconinck, Andrew A Lane, Naveen Pemmaraju, Francine Garnache Ottou
Cover image: Neoplastic cells infiltrating the skin in a diffuse and nodular pattern with epidermal and adnexal sparing. 100 magnification; hematoxylin and eosin.
Medical illustrations by Neil Smith, Salisbury, UK. Typesetting by Amnet, Chennai, India. Printed in the UK with Xpedient Print.
Contents
List of abbreviations
Introduction
What is BPDCN?
Diagnosis
Management
Unmet needs and future directions
Useful resources
Index
List of abbreviations
ALL: acute lymphoblastic leukemia
AML: acute myeloid leukemia
BPDCN: blastic plasmacytoid dendritic cell neoplasm
BSA: body surface area
CBC: complete blood count
CHOP: chemotherapy regimen comprising cyclophosphamide, hydroxydaunorubicin (doxorubicin), Oncovin (vincristine) and prednisone or prednisolone
CLS: capillary leak syndrome
CMML: chronic myelomonocytic leukemia
CNS: central nervous system
CR: complete remission
CSF: cerebrospinal fluid
CT: computed tomography
CTCL: cutaneous T-cell lymphoma
ECOG: Eastern Cooperative Oncology Group
EMA: European Medicines Agency
FDA: (US) Food and Drug Administration
HSCT: hematopoietic stem cell transplantation
Hyper-CVAD: two chemotherapeutic combinations given as hyperfractionated therapy - cyclophosphamide, vincristine, doxorubicin (Adriamycin) and dexamethasone, followed by methotrexate and cytarabine
IL: interleukin
IL3-R : interleukin-3 receptor
MDS: myelodysplastic syndrome
MPDCP: mature pDC proliferation
MRD: minimal/measurable residual disease
mSWAT: modified Severity-Weighted Assessment Tool
NK: natural killer (cell)
ORR: overall response rate
OS: overall survival
pDC: plasmacytoid dendritic cell
PET: positron emission tomography
PS: performance status
SSC: side scatter (plot)
WHO: World Health Organization
Introduction
At present, blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an orphan disease. Its real incidence is not known, but it is probably very low; it most often occurs in older men. BPDCN has only been recognized and identified in recent years and there remains much to be learned, for instance in terms of its genetics and molecular background. We now have the tools to clearly identify the disease, but appropriate treatment is still a challenge and no consensus exists regarding its management.
A major clinical characteristic of this hematodermic neoplasm is its highly aggressive behavior. Early diagnosis is critical to avoid a delay in the initiation of appropriate targeted treatment. While classic leukemia-based chemotherapy regimens achieve complete remission in most cases, the relapse rate is very high, with only a short duration of remission. Allogeneic hematopoietic stem cell transplantation, given during first complete remission, yields a significant survival advantage in eligible patients. Without it, almost all patients relapse, with expected survival of only 1 year.
Several targeted therapies against CD123, either alone or in combination, have recently been tested and described in numerous case reports and short series. To date, one new molecule, tagraxofusp, has been approved, in the USA and, more recently, in the EU.
Given the rarity of the disease and the nature of its clinical presentation, all dermatologists, hematologists, specialists in internal medicine and geriatricians must be aware of BPDCN as a rare but potential diagnosis, as well as the immediate specific management that needs to be implemented if there is to be any expectation of achieving a therapeutic result.
After reading this resource, physicians in all these disciplines should be able to recognize the clinical and biological features of BPDCN, and the overlap between its presentation and that of other hematolymphoid/leukemic malignancies. They should further be capable of implementing effective management based on the latest information.
1 What is BPDCN?
Classification
The first case description of a cutaneous agranular CD2-/CD4+/CD56+ lymphoma was reported in 1998. Over the following decade, several publications reported cases of CD4+/CD56+ hematodermic neoplasms, agranular CD4+ natural killer (NK)-cell leukemia and blastic NK-cell lymphomas. The natural history of these diseases is that of hematodermic malignant disease with cutaneous lesions, followed within a few weeks or months by leukemic transformation that rapidly becomes resistant to various chemotherapies. 1-3
In 2008, the fourth edition of the WHO s Classification of Tumours of Haematopoietic and Lymphoid Tissues clearly identified these diseases as a new category of tumor called blastic plasmacytoid dendritic cell neoplasm (BPDCN), belonging to the family of acute myeloid leukemia and related neoplasms . 4 In virtually all cases, these tumors are derived from a precursor of a specialized subset of dendritic cells called plasmacytoid dendritic cells (pDCs).
Further to this, in the 2016 fourth revised edition of the WHO classification, BPDCN was described as a distinct entity among the myeloid neoplasms ( Table 1.1 ). 5
Epidemiology
The incidence of BPDCN is difficult to determine with accuracy because of the lack of exhaustive data and specific registries. However, the authors estimate that BPDCN represents 0.44% of new hematologic neoplasms per year, that is, an incidence of 0.04 new patients per 100 000 people. This equates to approximately 700 new cases per year in the USA and 1000 new cases per year in Europe. 6 Complete data are not available in the EU. Patient series have been reported in France, Italy, Greece, Spain, Czech Republic, Turkey and Germany, but, with the exception of patients receiving hematopoietic stem cell transplantation (HSCT) who are reported to the European Society for Blood and Marrow Transplantation (EBMT) registry, no collaborative data are available. 7 , 8

TABLE 1.1
Classification of BPDCN
Myeloid neoplasms and acute leukemia
Myeloproliferative neoplasms (MPN)
Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA , PDGFRB or FGFR1 , or with PCM1-JAK2
Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
Myelodysplastic syndromes (MDS)
Acute myeloid leukemia (AML) and related neoplasms
Blastic plasmacytoid dendritic cell neoplasm *
- Blastic NK-cell lymphoma
- Agranular CD4+/CD56+ hematodermic neoplasm
- CD56+/TdT+ blastic NK-cell tumor
- CD4+/CD56+ lymphocyte-derived cutaneous lymphoma
Acute leukemias of ambiguous lineage
B-lymphoblastic leukemia/lymphoma
T-lymphoblastic leukemia/lymphoma
* A clinically aggressive neoplasm that is usually characterized at its onset by solitary or multiple skin lesions, often with associated regional lymphadenopathy. Many cases will ultimately progress to involve the blood and bone marrow as well. The blasts do not express myeloperoxidase or non-specific esterase; they are characterized by the expression of CD4, CD43, CD56, CD123, BDCA-2/CD303, TCL1 and CLA. CD7 and CD33 are not commonly expressed, and TdT is expressed in approximately 30% of cases. There is no expression of CD34 or CD117. Adapted from Arber et al. 2016. 5
Geography and ethnicity. BPDCN has been described worldwide, with many case reports and short series published from Europe, North America, South America, Japan and Korea. No clear ethnic differences have emerged. Although 75% of reported cases are in white individuals, publication bias in this respect precludes drawing robust conclusions. 2 , 3 , 6 , 7 , 9 In one large US study, there was a significantly lower disease incidence in all other races compared with the white population.
Age and sex. In France, there has been a specific registry for BPDCN for more than 15 years. In a recently published cohort of more than 100 patients, the median age was 64 years (11-89), with a 3:1 sex ratio in favor of males; 30 new patients were diagnosed per y