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

• Authors: HAUG Stefan; SPERR Wolfgang R.; WEHR Claudia; BONOFIGLIO Federico; KLEIN Saskia K.; KLUIN-NELEMANS Hanneke C.; MULDER Andre B.; HERMINE Olivier; ROSSIGNOL Julien; SUAREZ Felipe; MARCAIS Ambroise; SHOMALI William; PERKINS Cecelia; CHRISTEN Deborah; RABITSCH Werner; HADZIJUSUFOVIC Emir; VOGLOVA Jaroslava; JENTZSCH Madlen; SCHWAAB Juliana; LUBKE Johannes; MATTSSON Mattias; HAGGLUND Hans; DYBEDAL Ingunn; BAFFOE Daniel; BONNADONNA Patrizia; BONIFACIO Massimiliano; TANASI Ilaria; SCIUME Mariarita; NIEDOSZYTKO Marek; GORSKA Aleksandar; MITAL Andrzej; TRIGGIANI Massimo; PARENTE Roberta; YAVUZ Akif Selim; ELENA Chiara; MALCOVATI Luca; FERRARI Jacqueline; WORTMANN Friederike; BROCKOW Knut; FRANZ Tobias Michael; MAKRIS Michael; PAPAGEORGIOU Sotirios G.; BREYNAERT Christine; IEVEN Toon; ANGELOVA-FISCHER Irena; STEFAN Alex; VARKONYI Judit; SABATO Vito; SCHUG Tanja Daniela; VAN DAELE Paul L. A.; FORTINA Anna Belloni; CAROPPO Francesca; GULEN Theo; HEIZMANN Marc; HARTMANN Karin; RUFER Axel; DOUBEK Michael; PANSE Jens; GOTLIB Jason; AROCK Michel; OUDE ELBERINK Hanneke N. G.; REITER Andreas; VALENT Peter; SHOUMARIYEH Khalid
• Year of publication: 2026
• Type: Peer-reviewed scientific article
• Magazine / Source: EXPERIMENTAL HEMATOLOGY & ONCOLOGY
• MU Faculty or unit: Faculty of Medicine
• web: https://link.springer.com/article/10.1186/s40164-026-00819-8
• Doi: https://doi.org/10.1186/s40164-026-00819-8
• Keywords: Allogeneic stem cell transplantation; Systemic mastocytosis; Advanced systemic mastocytosis; Tyrosine kinase inhibitors; IPSM; MARS; KIT D816V
• Description: 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.