Subtype-specific outcome after allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis: a registry study of the European competence network on mastocytosis

Advanced systemic mastocytosis (AdvSM), comprising aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with an associated hematological neoplasm, is a heterogeneous myeloid neoplasm with poor prognosis. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative treatment, yet its benefit across AdvSM subtypes in the era of KIT-targeted tyrosine kinase inhibitors (TKIs) such as midostaurin and avapritinib remains unclear. To identify patient subgroups benefiting from allo-HCT and to define prognostic factors for post-transplant survival, we analyzed 631 AdvSM patients from the European Competence Network on Mastocytosis registry, including 69 who underwent allo-HCT. Treatment effects were assessed using time-dependent Cox regression in a transplant-eligible complete-case cohort (n = 419). In this cohort, allo-HCT showed no overall survival (OS) benefit (hazard ratio [HR] 1.21, 95% CI 0.80-1.84; p = 0.37), whereas TKI response emerged as a strong independent predictor of survival (HR 0.42; p<0.001). Subtype-stratified analysis revealed an allo-HCT benefit exclusively in patients with systemic mastocytosis associated with acute myeloid leukemia (n = 30; HR 0.20; p = 0.020). Among the 69 transplanted patients, median OS was 49.6 months with 2-year and 5-year survival of 63% and 46%, respectively. The International Prognostic Scoring System for Mastocytosis (IPSM) at transplantation independently predicted both OS (HR per category 1.68; p = 0.026) and progression-free survival (HR 1.99; p = 0.003), whereas the Mutation-Adjusted Risk Score and diagnostic subtype did not reach statistical significance. Competing risk analysis demonstrated that higher IPSM captured both relapse-related and transplant-related mortality. These findings suggest that the survival benefit of allo-HCT in AdvSM is driven primarily by control of the associated myeloid neoplasm. Accordingly, allo-HCT should be prioritized in patients with SM-AML, whereas TKI-directed strategies may be preferred in other subtypes, with IPSM at transplantation potentially guiding transplant selection and timing.

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Journal
Experimental Hematology and Oncology
Published
2026-08-20
DOI
https://doi.org/10.1186/s40164-026-00819-8
Primary Topic
Mast cells and histamine
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article
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article

Subtype-specific outcome after allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis: a registry study of the European competence network on mastocytosis

Jacqueline Ferrari, Akif Selim Yavuz, Paul Van Daele, Stefan Haug et al.
Experimental Hematology and Oncology
Mast cells and histamine
article

Subtype-specific outcome after allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis: a registry study of the European competence network on mastocytosis

Jacqueline Ferrari, Akif Selim Yavuz, Paul Van Daele, Stefan Haug, Deborah Christen, Mattias Mattsson, Tanja Schug, Emir Hadzijusufovic, Marc Heizmann, J Voglová, Friederike Wortmann, Sotirios G. Papageorgiou, Hanneke C. Kluin‐Nelemans, Francesca Caroppo, Anna Belloni Fortina, Toon Ieven, Axel Rüfer, Khalid Shoumariyeh, Theo Gülen, Johannes Lübke, Federico Bonofiglio, Mariarita Sciumé, Werner Rabitsch, Cecelia Perkins, Massimiliano Bonifacio, Ingunn Dybedal, Luca Malcovati, Roberta Parente, Claudia Wehr, Daniel Baffoe, André B. Mulder, Hanneke N.G. Oude Elberink, Alex Stefan, Judit Várkonyi, Tobias Michael Franz, Marek Niedoszytko, Chiara Elena, Christine Breynaert, Saskia K. Klein, Andrzej Mital, Wolfgang R. Sperr, Hans Hägglund, William Shomali, Ambroise Marcais, Juliana Schwaab, Jens Panse, Aleksandar Gorska, Jason Gotlib, Patrizia Bonnadonna, Michael Makris, Irena Angelova-Fischer, Julien Rossignol, Knut Brockow, Peter Valent, Andreas Reiter, Olivier Hermine, Michel Arock, Vito Sabato, Michael Doubek, Massimo Triggiani, Felipe Suarez, Madlen Jentzsch, Karin Hartmann, Ilaria Tanasi
article en

Abstract

Advanced systemic mastocytosis (AdvSM), comprising aggressive systemic mastocytosis, mast cell leukemia, and systemic mastocytosis with an associated hematological neoplasm, is a heterogeneous myeloid neoplasm with poor prognosis. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative treatment, yet its benefit across AdvSM subtypes in the era of KIT-targeted tyrosine kinase inhibitors (TKIs) such as midostaurin and avapritinib remains unclear. To identify patient subgroups benefiting from allo-HCT and to define prognostic factors for post-transplant survival, we analyzed 631 AdvSM patients from the European Competence Network on Mastocytosis registry, including 69 who underwent allo-HCT. Treatment effects were assessed using time-dependent Cox regression in a transplant-eligible complete-case cohort (n = 419). In this cohort, allo-HCT showed no overall survival (OS) benefit (hazard ratio [HR] 1.21, 95% CI 0.80-1.84; p = 0.37), whereas TKI response emerged as a strong independent predictor of survival (HR 0.42; p<0.001). Subtype-stratified analysis revealed an allo-HCT benefit exclusively in patients with systemic mastocytosis associated with acute myeloid leukemia (n = 30; HR 0.20; p = 0.020). Among the 69 transplanted patients, median OS was 49.6 months with 2-year and 5-year survival of 63% and 46%, respectively. The International Prognostic Scoring System for Mastocytosis (IPSM) at transplantation independently predicted both OS (HR per category 1.68; p = 0.026) and progression-free survival (HR 1.99; p = 0.003), whereas the Mutation-Adjusted Risk Score and diagnostic subtype did not reach statistical significance. Competing risk analysis demonstrated that higher IPSM captured both relapse-related and transplant-related mortality. These findings suggest that the survival benefit of allo-HCT in AdvSM is driven primarily by control of the associated myeloid neoplasm. Accordingly, allo-HCT should be prioritized in patients with SM-AML, whereas TKI-directed strategies may be preferred in other subtypes, with IPSM at transplantation potentially guiding transplant selection and timing.

Experimental Hematology and OncologyVol. 15(1)
Semmelweis University (HU), University of Verona (IT), Johannes Kepler University of Linz (AT), Uppsala University (SE), Oslo University Hospital (NO), Hôpital Necker-Enfants Malades (FR), University of Salerno (IT), University Medical Center Groningen (NL), Karolinska University Hospital (SE), University of Padua (IT), University of Antwerp (BE), Inserm (FR), University of Freiburg (DE), University of Groningen (NL), German Cancer Research Center (DE), University of Basel (CH), National and Kapodistrian University of Athens (GR), Medical University of Graz (AT), Université Paris Cité (FR), Charles University (CZ), Masaryk University (CZ), Heidelberg University (DE), Universitair Ziekenhuis Leuven (BE), University Medical Center Freiburg (DE), University Hospital Heidelberg (DE), University Hospital of Basel (CH), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Karolinska Institutet (SE), Sorbonne Université (FR), Institut Necker Enfants Malades (FR), Azienda Ospedaliera Universitaria Integrata Verona (IT), Graz University Hospital (AT), Assistance Publique – Hôpitaux de Paris (FR), Laboratoire National de Référence (MA), University Hospital Schleswig-Holstein (DE), Kepler Universitätsklinikum (AT), Luzerner Kantonsspital (CH), Pitié-Salpêtrière Hospital (FR), University Hospital Hradec Králové (CZ), University General Hospital Attikon (GR), Hôpitaux Universitaires de Strasbourg (FR), Policlinico San Matteo Fondazione (IT), National Research Council (IT), Kantonsspital Aarau (CH), Technical University of Munich (DE), Istanbul University (TR), Gdańsk Medical University (PL), Medical University of Vienna (AT), RWTH Aachen University (DE), Erasmus University Rotterdam (NL), Leipzig University (DE), University of Lübeck (DE), Stanford University (US), KU Leuven (BE)
National Science Foundation, Pfizer, Celgene, Jazz Pharmaceuticals, BeiGene, Cancer Research UK, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Austrian Science Fund, Fonds Wetenschappelijk Onderzoek, Associazione Italiana per la Ricerca sul Cancro, Servier, Vlaamse regering, Swiss Cancer Research Foundation, Medac, Grifols, Daiichi Sankyo Europe
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Mast cells and histamine
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