Subtype-specific outcome after allogeneic hematopoietic cell transplantation in advanced systemic mastocytosis: a registry study of the European competence network on mastocytosis
Year: 2026
Type: article
Study design: Observational Study
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.
Authors: Stefan Haug, Wolfgang R. Sperr, Claudia Wehr, Federico Bonofiglio, Saskia K. Klein, Hanneke C. Kluin-Nelemans, André B. Mulder, Olivier Hermine, Julien Rossignol, Felipe Suarez, Ambroise Marcais, William Shomali, Cecelia Perkins, Deborah Christen, Werner Rabitsch, Emir Hadzijusufovic, Jaroslava Voglová, Madlen Jentzsch, Juliana Schwaab, Johannes Lübke, Mattias Mattsson, Hans Hagglund, Ingunn Dybedal, Daniel Baffoe, Patrizia Bonnadonna, Massimiliano Bonifacio, Ilaria Tanasi, Mariarita Sciumè, Marek Niedoszytko, Aleksandar Gorska, Andrzej Mital, Massimo Triggiani, Roberta Parente, Akif Selim Yavuz, Chiara Elena, Luca Malcovati, Jacqueline Ferrari, Friederike Wortmann, Knut Brockow, Tobias Michael Franz, Michael Makris, Sotirios G. Papageorgiou, Christine Breynaert, Toon Ieven, Irena Angelova-Fischer, Alex Stefan, Judit Várkonyi, Vito Sabato, Tanja Daniela Schug, Paul L. A. van Daele, Anna Belloni Fortina, Francesca Caroppo, Theo Gulen, Marc Heizmann, Karin Hartmann, Axel Rüfer, Michael Doubek, Jens Panse, Jason Gotlib, Michel Arock, Hanneke N. G. Oude Elberink, Andreas Reiter, Peter Valent, Khalid Shoumariyeh
Institutions: University of Freiburg, University Medical Center Freiburg, Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, National Research Council, University Medical Center Groningen, University of Groningen, Hôpital Necker-Enfants Malades, Inserm, Université Paris Cité, Institut des Maladies Génétiques Imagine, Hôpitaux Universitaires de Strasbourg, Stanford Cancer Institute, Stanford University, Universitätsklinikum Aachen, RWTH Aachen University, Charles University, University Hospital Hradec Králové, University Hospital Leipzig, Leipzig University, Heidelberg University, University Medical Centre Mannheim, Uppsala University, Oslo University Hospital, Azienda Ospedaliera Universitaria Integrata Verona, University of Verona, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gdańsk Medical University, University of Salerno, Istanbul University, Policlinico San Matteo Fondazione, University Hospital Schleswig-Holstein, TUM Klinikum, Technical University of Munich, National and Kapodistrian University of Athens, University General Hospital Attikon, Universitair Ziekenhuis Leuven, KU Leuven, Johannes Kepler University of Linz, Kepler Universitätsklinikum, Semmelweis University, University of Antwerp, Medical University of Graz, Erasmus University Rotterdam, University of Padua, Karolinska University Hospital, Karolinska Institutet, Kantonsspital Aarau, University of Basel, University Hospital of Basel, University of Lucerne, Luzerner Kantonsspital, Masaryk University, Sorbonne Paris Cité, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,290
Funders: 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
Awards: G1165031887, Can behaviour analysis of individual mast cells and basophils lift the veil of anaphylaxis in mastocytosis?, G1447233184, G1925763459, Les nains dans l'Antiquité., G2442905659, G255694563, G2559588348, G2830544313, G3560809795, G3709999309, SFB 1453: Nephrogenetik (NephGen), G4473063359, G4854266585, G4988965809, G515567895, G6002391077, G7878577745, G8083589064, G8486413159
OpenAlex ID: W7203834995