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Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis


In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level ≥125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL.

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Fig. 1: Bone marrow histology of two patients with a diagnosis of D816V-mutated bone marrow mastocytosis included in this series.
Fig. 2: Long-term outcome of 300 patients with WHO-based bone marrow mastocytosis (BMM) and 859 patients with typical indolent systemic mastocytosis (ISMtyp).
Fig. 3: Prognosis of WHO-based bone marrow mastocytosis (BMM) according to risk.
Fig. 4: Prognostic comparison of patients with low-risk bone marrow mastocytosis (BMM) and other subgroups.

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The Authors gratefully acknowledge the contribution of Dr. Alice Parisi (Department of Diagnostics and Public Health, Section of Pathological Anatomy, University of Verona) for providing the histological images.


PV was supported by the Austrian Science Fund (FWF) grants P32470-B and F4704-B20. LM and CE were supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, Italy (Investigator Grant #20125; AIRC 5×1000 project #21267, International Accelerator project #22796).

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RZ, MB, PB, PV designed the study, analyzed and interpreted data, and wrote the paper. LS, BvA, HOE, JR, OH, AG, ML, EH, CM, SM, CP, WS, CE, AI, MJ, RP, FC, OS, AZ, MM, ASY, JP, JV, MD, VS, CB, VV, TS, HH, FW, KB, IAF, ABF, MT, AR, KH, LM, JG, KS, MN, MA, HKN recruited participants and contributed to data collection. GL and WRS performed statistical analyses. All Authors contributed to the review of the paper. All Authors agreed to be accountable for all aspects of the work.

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Correspondence to Massimiliano Bonifacio.

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Zanotti, R., Bonifacio, M., Lucchini, G. et al. Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis. Leukemia 36, 516–524 (2022).

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