Serum chemistry profiling and prognostication in systemic mastocytosis: a registry-based study of the ECNM and GREM.
Johannes LübkeAlicia SchmidDeborah ChristenJoanne N G Oude ElberinkLambert F R SpanMarek NiedoszytkoAleksandra GórskaMagdalena LangeKaroline V GleixnerEmir HadzijusufovicAlex StefanIrena Angelova-FischerRoberta ZanottiMassimiliano BonifacioPatrizia BonadonnaKhalid ShoumariyehNikolas von BubnoffSabine MüllerCecelia PerkinsChiara ElenaLuca MalcovatiHans G HagglundMattias MattssonRoberta ParenteJudit VarkonyiAnna Belloni FortinaFrancesca CaroppoKnut BrockowAlexander ZinkChristine BreynaertToon IevenAkif Selim YavuzMichael DoubekVito SabatoTanja SchugKarin HartmannMassimo TriggianiJason GotlibOlivier HermineMichel ArockHanneke C Kluin-NelemansJens Peter PanseWolfgang R SperrPeter ValentAndreas ReiterJuliana SchwaabPublished in: Blood advances (2024)
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 (ECNM) and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells (GREM) 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 (AP), ß2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P<0.001). With regard to subvariants of AdvSM, an elevated LDH ≥260U/L was associated with multi-lineage expansion (leukocytosis, r=0.37, P<0.001; monocytosis, r=0.26, P<0.001) and the presence of an associated myeloid neoplasm (P<0.001), whereas tryptase levels were highest in mast cell leukemia (MCL vs. non-MCL, 308 µg/L vs. 146 µg/L, P=0.003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to lactate dehydrogenase (HR 2.1 [95% CI 1.1-4.0], P=0.018) and 1.5 points each to ß2-microglobulin (HR 2.7 [95% CI 1.4-5.4], P=0.004) and albumin (HR 3.3 [95% CI 1.7-6.5], P=0.001) delineated a highly predictive three-tier risk classification system (0 points, 8.1 years vs. 1 point, 2.5 years, ≥1.5 points, 1.7 years; P<0.001). Moreover, serum chemistry parameters enabled further stratification of IPSM-AdvSM1/2 risk-score classified patients (P=0.027). In conclusion, serum chemistry profiling is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.