Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry

Kennedy, Vanessa E.; Perkins, Cecelia; Reiter, Andreas; Jawhar, Mohamad; Lübke, Johannes; Kluin-Nelemans, Hanneke C.; Shomali, William; Langford, Cheryl; Abuel, Justin; Hermine, Olivier; Niedoszytko, Marek; Górska, Aleksandra; Mital, Andrzej; Bonadonna, Patrizia; Zanotti, Roberta; Tanasi, Ilaria; Mattsson, Mattias; Hägglund, Hans; Triggiani, Massimo; Yavuz, Akif Selim; Panse, Jens; Christen, Deborah; Heizmann, Marc; Shoumariyeh, Khalid; Müller, Sabine; Elena, Chiara; Malcovati, Luca; Fiorelli, Nicolas; Wortmann, Friederike; Vučinić, Vladan; Brockow, Knut; Fokoloros, Christos; Papageorgiou, Sotirios G.; Breynaert, Christine; Bullens, Dominique; Doubek, Michael; Ilerhaus, Anja; Angelova-Fischer, Irena; Solomianyi, Oleksii; Várkonyi, Judit; Sabato, Vito; Rüfer, Axel; Schug, Tanja; Hermans, Maud A.W.; Fortina, Anna Belloni; Caroppo, Francesca; Bumbea, Horia; Gülen, Theo; Hartmann, Karin; Elberink, Hanneke Oude; Schwaab, Juliana; Arock, Michel; Valent, Peter; Sperr, Wolfgang R.; Gotlib, Jason

doi:10.1182/bloodadvances.2022008292

Cited by 25 publications

(70 citation statements)

References 31 publications

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“…Non-advanced SM subtypes are the most frequent and include BMM, ISM and SSM. Advanced SM includes ASM, SM-AHN (SM-AMN) and MCL [ 3 , 9 , 10 , 23 , 24 ].…”

Section: Overview On Mastocytosis Sm Diagnostic Criteria and Differen...mentioning

confidence: 99%

“…In 2013, Georgin-Lavialle et al reviewed clinico-pathologic data of 51 published MCL cases [ 4 ]; in 2017, Jawhar et al reviewed 28 cases of MCL diagnosed between 2008 and 2016 in Germany [ 5 ]; in 2017, Jain et al presented a single American center experience with 218 SM cases, among which 13 MCL were present [ 6 ]; more recently in 2022, Kennedy et al evaluated the largest cohort of MCL patients (92 cases) from the European Competence Network on Mastocytosis (ECNM) registry [ 9 ].…”

Section: Mcl: Defining Criteria Leukemic and Aleukemic Variants Prima...mentioning

confidence: 99%

“…Mast cell leukemia (MCL), which was first described by Joachim in 1906, represents the most uncommon form of systemic mastocytosis (SM) and is seen in less than 5% of all SM patients [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is characterized by the leukemic expansion of mostly immature mast cells (MCs) in the bone marrow (BM) and other organs, with organ damage and a poor prognosis in the majority of cases with a median overall survival (OS) of 1.6 years [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Under discussion is the real importance of sub-dividing MCL into the leukemic variant with at least 10% atypical/immature MCs in the peripheral blood (PB) and the aleukemic variant with less than 10% circulating MCs [ 10 ]. A recent report on the largest cohort of MCL patients has interestingly noted that the presence of any circulating MCs even below the 10% threshold may negatively impact prognosis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Mast Cell Leukemia: An Update with a Practical Review

Zanelli

Quintini

Magnasco

et al. 2023

Cancers

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Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included.

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“…Non-advanced SM subtypes are the most frequent and include BMM, ISM and SSM. Advanced SM includes ASM, SM-AHN (SM-AMN) and MCL [ 3 , 9 , 10 , 23 , 24 ].…”

Section: Overview On Mastocytosis Sm Diagnostic Criteria and Differen...mentioning

confidence: 99%

Section: Mcl: Defining Criteria Leukemic and Aleukemic Variants Prima...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Mast Cell Leukemia: An Update with a Practical Review

Zanelli

Quintini

Magnasco

et al. 2023

Cancers

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Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management

Pardanani

2023

American J Hematol

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Overview: Systemic mastocytosis (SM) results from clonal proliferation of mast cells (MC) in extracutaneous organs. Diagnosis: The major criterion is presence of multifocal MC clusters in the bone marrow and/or extracutaneous organs. Minor diagnostic criteria include elevated serum tryptase level, MC CD25/CD2/CD30 expression, and presence of activating KIT mutations. Risk Stratification: Establishing SM subtype as per the International Consensus Classification/World Health Organization classification systems is an important first step. Patients either have indolent/smoldering SM (ISM/SSM) or advanced SM, including aggressive SM (ASM), SM with associated myeloid neoplasm (SM-AMN), and mast cell leukemia. Identification of poor-risk mutations (i.e., ASXL1, RUNX1, SRSF2, NRAS) further refines the risk stratification. Several risk models are available to help assign prognosis in SM patients. Management: Treatment goals for ISM patients are primarily directed toward anaphylaxis prevention/symptom control/osteoporosis treatment. Patients with advanced SM frequently need MC cytoreductive therapy to reverse disease-related organ dysfunction. Tyrosine kinase inhibitors (TKI) (midostaurin, avapritinib) have changed the treatment landscape in SM. While deep biochemical, histological and molecular responses have been documented with avapritinib treatment, its efficacy as monotherapy against a multimutated AMN disease component in SM-AMN patients remains unclear. Cladribine continues to have a role for MC debulking, whereas interferon-α has a diminishing role in the TKI era. Treatment of SM-AMN primarily targets the AMN component, particularly if an aggressive disease such as acute leukemia is present. Allogeneic stem cell transplant has a role in such patients. Imatinib has a therapeutic role only in the rare patient with an imatinib-sensitive KIT mutation. | DISEASE OVERVIEW AND PATHOGENESISSystemic mastocytosis (SM) results from a clonal, neoplastic proliferation of morphologically and immunophenotypically abnormal mast cells (MC) that accumulate in one or more organ systems. 1,2 The sine qua non of mastocytosis is the presence of multifocal clusters of abnormal MC, which in contrast to normal MC are variable in appearance, ranging from round to fusiform variants with long, polar cytoplasmic processes, and may display cytoplasmic hypogranularity with

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The international consensus classification of eosinophilic disorders and systemic mastocytosis

et al. 2023

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Based on new data and increased understanding of disease molecular genetics, the international consensus classification (ICC) has made several changes in the diagnosis and classification of eosinophilic disorders and systemic mastocytosis. Myeloid/lymphoid neoplasms with eosinophilia (M/LN‐eo) and gene rearrangements have been renamed as M/LN‐eo with tyrosine kinase gene fusions (M/LN‐eo‐TK). The category has been expanded to include ETV6::ABL1 and FLT3 fusions, and to accept PCM1::JAK2 and its genetic variants as formal members. The overlaps and differences between M/LN‐eo‐TK and BCR::ABL1‐like B‐lymphoblastic leukemia (ALL)/de novo T‐ALL sharing the same genetic lesions are addressed. Besides genetics, ICC for the first time has introduced bone marrow morphologic criteria in distinguishing idiopathic hypereosinophilia/hypereosinophilic syndrome from chronic eosinophilic leukemia, not otherwise specified. The major diagnostic criteria for systemic mastocytosis (SM) in the ICC remain largely based on morphology, but several minor modifications/refinements have been made in criteria related to diagnosis, subclassification, and assessment of disease burden (B‐ and C‐findings). This review is to focus on the ICC updates related to these disease entities, illustrated through changes related to morphology, molecular genetics, clinical features, prognosis, and treatment. Two practical algorithms are provided in navigating through the diagnosis and classification systems of hypereosinophilia and SM.

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Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry

Cited by 25 publications

References 31 publications

Mast Cell Leukemia: An Update with a Practical Review

Mast Cell Leukemia: An Update with a Practical Review

Systemic mastocytosis in adults: 2023 update on diagnosis, risk stratification and management

The international consensus classification of eosinophilic disorders and systemic mastocytosis

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