Smoldering mastocytosis: Survival comparisons with indolent and aggressive mastocytosis

Tefferi, Ayalew; Shah, Sahrish; Reichard, Kaaren K.; Hanson, Curtis A.; Pardanani, Animesh

doi:10.1002/ajh.25302

Cited by 16 publications

(17 citation statements)

References 5 publications

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“…In an updated report, the median overall survival (OS) of 17 SSM patients was found to be significantly inferior when compared to 274 ISM patients (HR 5.5, 95% CI 2.8–10.2). This difference was accounted for by a higher prevalence of poor‐risk features in SSM patients, including, in particular, older age and hemoglobin below the lower limit of the sex‐adjusted reference range 74 . In contrast, BMM patients more frequently presented with MCMRS (86%), including anaphylaxis (78%), but had a more favorable survival outcome 55 .…”

Section: Risk Stratificationmentioning

confidence: 99%

Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management

2021

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Overview Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in extra‐cutaneous organs. Diagnosis The major criterion is presence of multifocal clusters of spindled MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. Risk Stratification Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM‐AHN), and mast cell leukemia (MCL). Identification of poor‐risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical‐molecular risk models have been developed to more accurately assign prognosis in SM patients. Management Treatment goals for ISM patients are primarily directed towards anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease‐related organ dysfunction. High response rates have been seen with small‐molecule inhibitors that target mutant‐KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon‐α, although head‐to‐head comparisons are lacking. Treatment of SM‐AHN primarily targets the AHN component, particularly if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib‐sensitive KIT mutations.

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Section: Risk Stratificationmentioning

confidence: 99%

Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management

2021

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“…In an updated report, the median overall survival (OS) of 17 SSM patients was found to be significantly inferior when compared to 274 ISM patients (HR 5.5, 95% CI 2.8‐10.2). This difference was accounted for by a higher prevalence of poor‐risk features in SSM patients, including, in particular, older age and hemoglobin below the lower limit of the sex‐adjusted reference range . In contrast, BMM patients more frequently presented with MCMRS (86%), including anaphylaxis (78%), but had a more favorable survival outcome .…”

Section: Risk Stratificationmentioning

confidence: 99%

Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management

2019

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Overview Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra‐cutaneous organs. Diagnosis The major criterion is presence of multifocal clusters of abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC CD25 expression, and presence of KITD816V mutation. Risk stratification Establishing SM subtype as per the World Health Organization classification system is an important first step. Broadly, patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, the latter includes aggressive SM (ASM), SM with associated hematological neoplasm (SM‐AHN), and mast cell leukemia (MCL). Identification of poor‐risk mutations (ie, ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Recently, clinical and hybrid clinical‐molecular risk models have been developed to more accurately assign prognosis in SM patients. Management ISM patients have a normal life expectancy and treatment is generally limited to anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to ameliorate disease‐related organ dysfunction. High response rates have been seen with small‐molecule inhibitors that target mutant‐KIT, including midostaurin (Food and Drug Administration approved) or avapritinib (investigational). Other options for MC cytoreduction include cladribine or interferon‐α, although head‐to‐head comparisons are lacking. Treatment of SM‐AHN primarily targets the AHN component, if an aggressive disease such as acute myeloid leukemia is present. Allogeneic stem cell transplant can be considered in such patients, or in those with relapsed/refractory advanced SM. Imatinib has a limited therapeutic role in SM; effective cytoreduction is limited to those with imatinib‐sensitive KIT mutations.

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“…For a good reason, historic concerns with profound mast cell disease, commonly referred to as mastocytosis, have captured the majority of attention [37]. Whether smoldering or frankly neoplastic, the implications for an aggressive proliferation can be devastating [38]. The latter forms of illness dominated interests given the need for acute intervention for what proved to be largely clonal mast cell proliferations.…”

Section: Non-clonal Mast Cell Activation Disordermentioning

confidence: 99%

“…Mast cells mature at their peripheral organ site after progenitor cells migrate through the circulation [121]. The site of such maturation will influence the nature of mast cell granule composition [38]. Mast cells in different tissues (e.g., mucosal versus connective tissue) can be distinguished by their granule contents [122,123].…”

Section: The Mast Cell As the Potential Common Denominatormentioning

confidence: 99%

Mast Cell Biology and Linkages for Non-clonal Mast Cell Activation and Autoimmune/Inflammatory Syndrome Induced by Adjuvants

Cimolai

2020

SN Compr. Clin. Med.

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Non-clonal mast cell activation disorder (syndrome) (NC-MCAD) and autoimmune/inflammatory syndrome induced by adjuvants (ASIA) are complex syndromic and spectral clinical entities which have contemporaneously garnered considerable attention and rightfully so. NC-MCAD presents with a predominantly allergic profile, and causative clinical variables may or may not be identified. Manifest NC-MCAD illnesses can be complex and involve several organ systems. Such diversity may be in part explained by the ubiquity and plasticity of the mast cell. ASIA, due to its broad definition, continues to expand as a clinical entity, especially with the greater recognition of what might constitute adjuvancy. Such diversity has the potential to overly stretch the boundaries for scientific investigation. For both NC-MCAD and ASIA, the inciting molecular mechanisms require elucidation. Future research would benefit from greater precision for clinical diagnosis and risk factor identification, and the latter would be potentially facilitated by the discovery of reliable laboratory markers. Some patients with ASIA may present with clinical features that may be identified as NC-MCAD. This review examines the potential spectral nexus of NC-MCAD and ASIA and considers the role of the mast cell in such a possible interface.

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Smoldering mastocytosis: Survival comparisons with indolent and aggressive mastocytosis

Cited by 16 publications

References 5 publications

Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management

Systemic mastocytosis in adults: 2021 Update on diagnosis, risk stratification and management

Systemic mastocytosis in adults: 2019 update on diagnosis, risk stratification and management

Mast Cell Biology and Linkages for Non-clonal Mast Cell Activation and Autoimmune/Inflammatory Syndrome Induced by Adjuvants

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