Systemic Mastocytosis in 910 Patients: Prognostic Contribution of the International Consensus Classification in the Context of the Mayo Alliance Prognostic System.

The current study includes 910 patients with systemic mastocytosis (SM) seen at the Mayo Clinic from 1968 to 2024. The primary objective was to examine the prognostic contribution of the International Consensus Classification (ICC), in the context of the Mayo Alliance Prognostic System (MAPS) for SM. World Health Organization classification (WHO-HAEM5) subcategories included (i) indolent/smoldering SM (ISM/SSM; N = 518), (ii) SM associated with another hematological neoplasm (SM-AHN; N = 273), with the latter including both myeloid and lymphoid neoplasms, (iii) aggressive SM (ASM; N = 106), and (iv) WHO-defined mast cell leukemia (MCL; N = 13), which included mast cells with both "mature" and "immature" morphology. The ICC-defined subcategories were mostly similar with the exception that SM-AHN was replaced by SM associated with another myeloid neoplasm (SM-AMN; N = 235) and WHO-defined MCL was replaced by ICC-defined MCL (N = 8), which included only those with immature MC morphology. Overall survival (OS) was similar between WHO-defined MCL (median 1.8 years) vs. SM-AHN (median 2.3 years; p = 0.3) but significantly different between ICC-defined MCL (median 0.08 years) vs. SM-AMN (median 2.0 years; p < 0.01). Significant difference in OS was also apparent between ICC-defined SM-AMN and SM associated with lymphoid neoplasm (SM-ALN; median 8.1 years; HR 3.4; p < 0.01). Multivariable analysis confirmed the inter-independent prognostic contributions of both ICC-defined morphologic subcategories and MAPS risk variables, including age > 60 years, anemia, alkaline phosphatase > ULN, and platelet count < 150 × 109/L (p < 0.03 in all instances); the same was not true for WHO-HAEM5-defined SM subcategories. The addition of mutational information into the multivariable model resulted in ousting anemia and inclusion of ASXL1 (p < 0.01), SRSF2 (p = 0.01), and NRAS (p = 0.01) mutations as additional risk factors. Classification of SM by ICC is prognostically more accurate, compared to WHO-HAEM5, and strengthens the prognostic contribution of morphology to current clinical and molecular risk models.