Prognostic impact of splenomegaly, hepatomegaly and lymphadenopathy in mastocytosis
Published: November 16, 2022
Mastocytosis is a rare and heterogenous disorder with both cutaneous and systemic manifestations. Uncontrolled mast cell accumulation and activation may lead to manifold clinical symptoms. They vary in severity and range from flushing, pruritus, diarrhea, abdominal cramping, bone pain to life-threatening complications including anaphylactic shock. According to the revised 2022 World Health Organization (WHO-5) classification, systemic mastocytosis (SM) is differentiated between non-advanced and advanced subtypes. Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy (with and without subsequent organ damage) is recognized as an important diagnostic and prognostic feature by the WHO-5 classification. However, previous studies about the potential relevance of organomegaly were often limited to smaller cohorts and a more detailed investigation of prevalence and prognostic impact of organomegaly was lacking.
In a retrospective study recently published in The Journal of Allergy and Clinical Immunology: In Practice, Lübke and colleagues therefore investigated the prevalence and prognostic impact of one or more organomegalies on clinical course and survival in 3155 patients enrolled within the European Competence Network on Mastocytosis (ECNM). The ECNM registry was established in 2012 as a multidisciplinary, multi-national cooperative initiative to analyze basic clinical, laboratory and prognostic parameters in patients with cutaneous and systemic mastocytosis. Strengths of this registry-based study included (i) a high number of patients, (ii) a comprehensive data set of baseline and on-treatment parameters, (iii) data clearing and updated follow-ups once a year.
Prevalence of organomegaly including lymphadenopathy was more often recognized in advanced SM (73%) than in non-advanced SM (7.5%) patients. In advanced SM, splenomegaly (44%) was the most common organomegaly. The median overall survival of SM patients without any signs of organomegaly versus presence of 3 organomegalies varied between 26.9 and 2.8 years. Subgroup analyses revealed that the strong prognostic impact of organomegaly was evident in both non-advanced and advanced SM patients. Presence and number of organomegalies were further associated with an aggressive disease phenotype. At time of disease progression, a previously unknown organomegaly was observed in 38-43% of patients (depending on initial SM subtype) with new splenomegaly (12% in non-advanced and 19% in advanced SM) being the most common event. The majority of patients with a dynamic (expanding) organomegaly had no signs of an enlarged organ at diagnosis. Assignment of 1 point each to splenomegaly and alkaline phosphatase levels >150 U/L validated an easily accessible and highly predictive risk stratification system for SM patients. Median OS of low- (0 points), intermediate- (1 point) and high-risk (2 points) patients was 26.9, 12.4 and 2.6 years. The results highlight the medical need for identification and close monitoring of organomegaly in SM patients through repeated adequate physical/radiography examinations as a potential early indicator of progression and adverse outcome allowing early intervention to prevent further organ damage.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.