Lübke, Johannes (Heidelberg University) Schwaab, Juliana (Heidelberg University) Triggiani, Massimo (University of Salerno,) Hartmann, Karin (University of Basel) Schug, Tanja (University Hospital Graz) Sabato, Vito (University of Antwerp) Doubek, Michael (Masaryk University) Yavuz, Akif Selim (University of Istanbul) Leven, Toon (University Hospitals Leuven) Breynaert, Christine (University Hospitals Leuven) Zink, Alexander (Technical University of Munich) Brockow, Knut (Technical University of Munich) Reiter, Andreas (Heidelberg University) Caroppo, Francesca (University of Padova) Fortina, Anna Belloni (University of Padova) Varkonyi, Judit (Varkonyi) Parente, Roberta (University of Salerno) Mattsson, Mattias (Uppsala University) Hagglund, Hans (Uppsala University) Malcovati, Luca (Fondazione I.R.C.C.S. Policlinico San Matteo) Elena, Chiara (Fondazione I.R.C.C.S. Policlinico San Matteo) Perkins, Cecelia (Stanford University) Müller, Sabine (University of Freiburg) Valent, Peter (Medical University of Vienna) von Bubnoff, Nikolas (University of Freiburg / German Cancer Consortium) Shoumariyeh, Khalid (University of Freiburg / German Cancer Consortium) Bonadonna, Patrizia (Verona University Hospital) Bonifacio, Massimiliano (Verona University Hospital) Zanotti, Roberta (Verona University Hospital) Angelova-Fischer, Irena (Johannes Kepler University) Stefan, Alex (Johannes Kepler University) Hadzijusufovic, Emir (University of Veterinary Medicine Vienna / Medical University of Vienna) Karoline V, Karoline V. (Medical University of Vienna) Lange, Magdalena (Medical University of Gdańsk) Sperr, Wolfgang R. (Medical University of Vienna) Gorska, Aleksandra (Medical University of Gdańsk) Niedoszytko, Marek (Medical University of Gdańsk) Schmid, Alicia (Heidelberg University) Christen, Deborah (RWTH Aachen University / Center for Integrated Oncology) Oude Elberink, Hanneke N. G. (University of Groningen) Span, Lambert F. R. (University of Groningen) Panse, Jens (RWTH Aachen University / Center for Integrated Oncology) Kluin-Nelemans, Hanneke C. (University of Groningen) Arock, Michel (University Paris) Hermine, Olivier (University Paris) Gotlib, Jason (Stanford University) Humans; Mastocytosis, Systemicdiagnosisblood; Prognosis; Registries; Male; Female; Middle Aged; Adult; Aged; Biomarkersblood; Tryptasesblood article 2024 doi:10.1182/bloodadvances.2024012756 https://phaidra.vetmeduni.ac.at/o:3264 eng application/pdf Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM CC BY-NC-ND 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Elsevier Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most specific serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, β2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308μg/L vs 146μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants. Blood Advances 8(11), 2890-2900 (2024)