Fast Facts: Systemic Mastocytosis

Cem Akin, Deepti H. Radia

Description

Systemic mastocytosis (SM) is a heterogeneous group of rare hematologic neoplasms that are characterized by clonal proliferation of mast cells in the bone marrow and extracutaneous organs, which can cause symptoms due to mast-cell mediator release and end-organ damage due to mast-cell infiltration. Mastocytosis is classified as a distinct entity by the WHO because of its unique clinicopathological features. Over 95% of patients harbor the somatic KIT driver mutation D816V. This book focuses on the diagnosis of SM, with up-to-date practical guidance on the management of patients with SM, who may present to a variety of healthcare providers on their diagnostic journey. It will be invaluable to clinicians, medical students, nurses, pharmacists and scientists in understanding the clinical, diagnostic and management challenges associated with SM. Table of Contents: • Definitions and classification • Epidemiology and pathophysiology • Diagnosis • Management of non-advanced systemic mastocytosis • Management of advanced systemic mastocytosis • Future directions

Sujets

• Hermatology
• Medical
• Médecine
• Hematology

Informations

• Publié par: S. Karger AG
• Date de parution: 04 avril 2023
• Nombre de lectures: 0
• EAN13: 9783318072006
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

Fast Facts for Healthcare Professionals
Systemic Mastocytosis
Deepti H Radia MD MRCPI FRCPath
Haematology Consultant, Department of Haematology
Guy s and St Thomas NHS Foundation Trust
London, UK
Cem Akin MD PhD
Professor of Medicine, Division of Allergy
and Clinical Immunology
Department of Internal Medicine
University of Michigan
Ann Arbor, Michigan, USA

Declaration of Independence
This book is as balanced and practical as we can make it.
Ideas for improvement are always welcome: [e-mail]
Fast Facts: Systemic Mastocytosis
First published 2023
Text 2023 Deepti H Radia, Cem Akin
2023 in this edition S. Karger Publishers Ltd
S. Karger Publishers Ltd, Merchant House, 5 East St Helen Street, Abingdon, Oxford OX14 5EG, UK
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ISBN 978-3-318-07161-0
Radia DH (Deepti)
Fast Facts: Systemic Mastocytosis/
Deepti H Radia, Cem Akin
Medical illustrations by Graeme Chambers, Belfast, UK.
Typesetting by Amnet, Chennai, India.
Printed in the UK with Xpedient Print.
Contents
List of abbreviations
Introduction
Definitions and classification
Epidemiology and pathophysiology
Diagnosis
Management of non-advanced systemic mastocytosis
Management of advanced systemic mastocytosis
Future directions
Useful resources
Index
List of abbreviations
AdvSM: advanced systemic mastocytosis
AE: adverse event
AHN: associated hematologic neoplasm
allo-HCT: allogeneic hematopoietic stem cell transplantation
ALP: alkaline phosphatase
AML: acute myeloid leukemia
ASA: acetylsalicylic acid (aspirin)
ASM: aggressive systemic mastocytosis
BMD: bone mineral density
BMM: bone marrow mastocytosis
CBC: complete blood count
CEL: chronic eosinophilic leukemia
CI: confidence interval
CM: cutaneous mastocytosis
CMML: chronic myelomonocytic leukemia
CNS: central nervous system
CR: complete remission
CRh: complete remission with partial hematologic recovery
CT: computed tomography
CysLT: cysteinyl leukotriene
DEXA: dual-energy X-ray absorptiometry
DOR: duration of response
ECNM: European Competence Network on Mastocytosis
EMA: European Medicines Agency
FDA: US Food and Drug Administration
FLT3: Fms-related tyrosine kinase 3
GI: gastrointestinal
GPSM: Global Prognostic Score for Mastocytosis
HaT: hereditary tryptasemia
HLA: human leukocyte antigen
HVA: Hymenoptera venom allergy
IFN- : interferon-
IgE: immunoglobulin E
IL: interleukin
IPSM: International Prognostic Scoring System for Mastocytosis
ISM: indolent systemic mastocytosis
IWG: International Working Group
LDH: lactate dehydrogenase
LT: leukotriene
MARS: Mutation-Adjusted Risk Score for Advanced Systemic Mastocytosis
MCAS: mast cell activation syndrome
MCL: mast cell leukemia
MCS: mast cell sarcoma
MDS: myelodysplastic syndrome
MIS: mastocytosis in the skin
MPCM: maculopapular cutaneous mastocytosis
MPN: myeloproliferative neoplasm
MQLQ: Mastocytosis Quality of Life Questionnaire
MRI: magnetic resonance imaging
MRT: Myeloproliferative Neoplasms Research and Treatment
MSAF: Mastocytosis Symptom Assessment Form
NCCN: National Comprehensive Cancer Network
NSAID: non-steroidal anti-inflammatory drug
ORR: overall response rate
OS: overall survival
PCR: polymerase chain reaction
PDGFR- / : platelet-derived growth factor receptor- /
PET: positron emission tomography
PFS: progression-free survival
PGD2: prostaglandin D2
PR: partial response
PUVA: psoralen plus UVA
RANKL: receptor activator of nuclear factor B ligand
REMA: Red Espa ola de Mastocitosis (Spanish Network on Mastocytosis)
SAE: severe adverse event
S/A/R: SRSF2, ASXL1 and RUNX1 (gene panel)
SCF: stem cell factor
SM: systemic mastocytosis
SM-AHN: systemic mastocytosis with an associated hematologic neoplasm
SSM: smoldering systemic mastocytosis
TKI: tyrosine kinase inhibitor
UP: urticaria pigmentosa
VAF: variant allele fraction
VIT: venom immunotherapy
WHO: World Health Organization
Introduction
Systemic mastocytosis (SM) is a heterogeneous group of rare hematologic neoplasms that are characterized by clonal proliferation of mast cells in the bone marrow and extracutaneous organs, which can cause symptoms due to mast-cell mediator release and end-organ damage due to mast-cell infiltration. Mastocytosis is classified as a distinct entity in the WHO s 2022 Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms because of its unique clinicopathological features. Over 95% of patients harbor the somatic KIT driver mutation D816V. SM can be divided into advanced and non-advanced forms based on the presence of organ dysfunction due to mast-cell infiltration, the presence of a non-mast-cell hematologic neoplasm and prognosis. While the majority of patients will have a diagnosis of non-advanced SM (indolent SM, bone marrow mastocytosis or smoldering SM), a small proportion will present with advanced SM (aggressive SM, SM with an associated hematologic neoplasm or mast cell leukemia).
This book focuses on the diagnosis of SM and the clinical heterogeneity of patients, with up-to-date practical guidance on the management of patients with SM, who may present to a variety of healthcare providers on their diagnostic journey. It will be invaluable to clinicians, medical students, nurses, pharmacists and scientists in understanding the clinical, diagnostic and management challenges associated with SM.
1 Definitions and classification
Priya Sriskandarajah
Department of Haematology
Guy s and St Thomas NHS Foundation Trust
London, UK
Mastocytosis is a group of disorders characterized by the clonal proliferation of abnormal mast cells, which then accumulate in the skin, bone marrow and other extracutaneous organs. Mastocytosis is classified as a distinct myeloid neoplasm in the WHO s 2022 Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms because of its unique clinical and pathological features. 1
Mastocytosis is divided into three broad subtypes: cutaneous mastocytosis (CM) systemic mastocytosis (SM) mast cell sarcoma (MCS).
This chapter provides a brief overview of these three subtypes with an emphasis on SM.
Cutaneous mastocytosis
CM is limited to the skin and is most frequently seen in children. CM is characterized by the presence of atypical mast cells within the dermis, with no evidence of mast-cell infiltration in the bone marrow or other extracutaneous organs. 2 CM is often diagnosed based on the presence of characteristic skin lesions that can be confirmed by skin biopsy if needed, with approximately 50% of affected children developing lesions before the age of 6 months. CM is subdivided into three categories based on the macroscopic features of lesions: 1 maculopapular cutaneous mastocytosis (MPCM), which is also known as urticaria pigmentosa (UP) diffuse CM mastocytoma of the skin.
Diffuse CM and mastocytoma occur almost exclusively in children. MPCM is the most prevalent category, is seen in both children and adults, and can be described as polymorphic (more common in children, lesions of various sizes) or monomorphic (more common in adults, small lesions of uniform size) on the basis of lesion appearance. Children with CM generally experience a self-limited disease course with lesions improving or resolving by adolescence, hence diagnostic procedures for SM are not indicated; however, 10% of children may have persistent disease and be diagnosed with SM. A good prognosis is associated with early onset of lesions (within the neonatal period), disease that is limited to the skin, and mastocytoma and polymorphic variants. Late onset of skin lesions (especially after 2 years of age), increasing serum tryptase levels, persistent or increasing skin lesions beyond puberty, or any signs of hematologic disease (such as hepatosplenomegaly or abnormalities in complete blood counts [CBCs] with differential) warrant investigation for SM. 3
Unlike CM in children, where systemic involvement is rare, patients with adult-onset skin lesions of mastocytosis often experience systemic disease with infiltration of the bone marrow. Characteristics of skin lesions can also differ; adults typically present with small, monomorphic lesions, whereas children tend to have larger, polymorphic lesions. 4 Rarely, patients may present with adult-onset skin lesions but without evidence of SM. These patients generally have a low mast-cell burden and normal or mildly elevated tryptase levels. Spontaneous resolution is rarer than with childhood-onset CM.
Finally, CM should be differentiated from mastocytosis in the skin (MIS). CM is a category of mastocytosis that excludes systemic involvement, and is the most appropriate category to assign to children for whom bone marrow biopsies looking for sy