Systemic mastocytosis: evolving lessons from large patient registry datasets

Abstract

Systemic mastocytosis (SM) is a clinically heterogeneous and relatively infrequent chronic myeloproliferative neoplasm [1]. In the Danish nationwide cohort study, the incidence and prevalence rates were 0.89 per 100,000 inhabitants per year and 9.59 per 100,000 inhabitants, respectively, for the period between 1997 and 2010 [2]. 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]. 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. The latter aspect ensured the use of relatively state-of-the-art diagnostic testing in the current study, which is not the case in older studies wherein a significant subset of patients was diagnosed prior to the development of such tests. A downside, however, of the recency bias in the article by Pieri et al. is the short patient follow up which limits the conclusions one might draw regarding clinical outcomes in SM patients.There are several additional observations that flow from the above two points: first, while the study by Pieri et al. includes 460 patients, as compared with the erstwhile largest study of 342 patients from the Mayo Clinic group [8], it is unclear whether either study is generalizable to the SM patient at large. While both were multidisciplinary studies, the former is predominantly a study of ISM patients (89% of all cases), likely reflecting a bias toward patient enrollment via dermatology and/or allergy clinics (73% had allergy/anaphylaxis symptoms). In contrast, the study by Lim et al. exhibited a hematology bias with 46% and 40% presenting with ISM and SM with associated clonal non-mast cell lineage disease (SM-AHNMD), respectively. This has to be taken into account when ex...

Cytogenetic abnormalities in systemic mastocytosis: WHO subcategory‐specific incidence and prognostic impact among 348 informative cases

“…However, the current study confirms the infrequent occurrence of cytogenetic abnormalities, in the absence of an associated another hematologic malignancy (ie, in ISM and ASM), although the additional observation regarding prognostic relevance requires validation in a larger study, which will probably require multi‐center collaboration. On the other hand, the number of informative cases in SM‐AHN‐myeloid was sufficient enough to examine its prognostic interaction with mutations and other previously established risk factors . In this regard, we found the prognostic contribution of abnormal karyotype in SM‐AHN‐myeloid, which was apparent in univariate analysis, to be undermined by that of adverse mutations, anemia and thrombocytopenia.…”

Comprehensive Review of Mastocytosis From Pathophysiology to Management Strategies

“…The occurrence of this disease is increasingly observed in society, which may be due to greater awareness and improved diagnostic methods. [8] Mastocytosis can manifest in individuals of all ages, spanning from childhood to adulthood. Among adults, the condition shows no particular age bias, although mortality rates tend to be higher in older individuals.…”

Smoldering mastocytosis: Survival comparisons with indolent and aggressive mastocytosis

“…Over the last two decades, the novel anti-myeloma drugs in combination with autologous hematopoietic stem cell transplantation (auto-HCT) have increased overall survival (OS) in younger (age < 65) MM patients. Increasing life expectancy of the general population and survival rates in younger MM patients has led to a substantial rise in the prevalence of geriatric MM population 4,5. Increasing life expectancy of the general population and survival rates in younger MM patients has led to a substantial rise in the prevalence of geriatric MM population 4,5.…”