International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis

Abstract

Systemic mastocytosis (SM) is characterized by accumulation of neoplastic mast cells and is classified into indolent and aggressive forms. The latter include aggressive SM (ASM), mast cell leukemia (MCL), and SM associated with a myeloid neoplasm wherein 1 or both disease compartments exhibit advanced features. These variants, henceforth collectively referred to as advanced SM for the purposes of this report, are typically characterized by organ damage and shortened survival duration. In contrast to indolent SM, in which symptoms are usually managed by noncytotoxic antimediator therapy, cytoreduction is usually necessary for disease control in advanced SM. Unfortunately, current drug treatment of these patients rarely results in complete clinical and histopathologic remissions or improved survival time. Previously defined response criteria were adapted to the heterogeneous presentations of advanced SM and the limited effects of available drugs. However, recent advances in understanding the molecular pathogenesis of SM and the corresponding prospect in targeted therapy make it a priority to modify these criteria. Our current study is the product of an international group of experts and summarizes the challenges in accomplishing this task and forwards a new proposal for response criteria, which builds on prior proposals and should facilitate response evaluation in clinical trials.

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

“…The panel recognized the highly subjective nature of the assessment of spleen and liver size by physical examination, and therefore recommended objective confirmation by CT/MRI. 20,21 In comparison to splenomegaly, hepatomegaly was significantly less frequently observed in patients with advSM, and only rarely in ISM. Of note, hepatomegaly was strongly associated with the presence of splenomegaly but not vice versa.…”

Systemic mastocytosis in adults: 2015 update on diagnosis, risk stratification, and management

“…Predictors of poor overall survival were presence of MCL (versus ASM or SM-AHNMD), reduced-intensity (versus myeloablative) conditioning and diseaseprogression (versus response or stable disease). Recently published consensus criteria will facilitate objective and standardized assessment of treatment response in patients with advanced SM in the era of novel, molecularly targeted drugs [78]. Currently used agents for SM therapy are presented below.…”

Systemic mastocytosis: evolving lessons from large patient registry datasets

“…There are two aspects of special note related to the study by Pieri et al First, it represents the largest study of SM patients diagnosed by WHO 2008 criteria ever published [5]. Second, patients in this study were diagnosed relatively recently, with 75% being diagnosed between the years 2009 and 2014.…”

“…Similarly, in the Groningen region, The Netherlands, prevalence of indolent SM (ISM) was estimated at 13 per 100,000 inhabitants, albeit with a roughly five-to sixfold increase in cases from 1998 to 2010, the latter likely relating to a recent increased awareness of SM combined with advances in diagnostic testing and expertise in specialized centers for this disease [3]. The increasing number of cases diagnosed with SM at least partly reflects the development of standardized diagnostic, classification and treatment-response criteria by international collaborative organizations such as the World Health Organization (WHO) and European Competence Network on Mastocytosis (ECNM) [4][5][6]. Prior to these larger-scale projects, most SM related data emerged from single center or single country registry studies, which despite their inherent limitations helped establish the early foundational principles of SM evaluation and treatment [7][8][9][10][11][12][13].…”

“…Prior to these larger-scale projects, most SM related data emerged from single center or single country registry studies, which despite their inherent limitations helped establish the early foundational principles of SM evaluation and treatment [7][8][9][10][11][12][13]. The article by Pieri et al in the current issue of the American Journal of Hematology represents a large study of SM patients from 10 Italian centers with dedicated mastocytosis programs participating in the Italian Registry of Mastocytosis [14].There are two aspects of special note related to the study by Pieri et al First, it represents the largest study of SM patients diagnosed by WHO 2008 criteria ever published [5]. Second, patients in this study were diagnosed relatively recently, with 75% being diagnosed between the years 2009 and 2014.…”