Systémová mastocytóza (SM) je onemocnění charakterizované proliferací klonálních mastocytů. Biologická povaha SM zahrnuje celé spektrum, od relativně benigní indolentní formy až po mastocytární leukemii. Klinický obraz osciluje od téměř asymptomatických forem, přes různě vyjádřené stupně mediátorového syndromu, až po nádorový syndrom spojený s hepatosplenomegalií, lymfadenopatií a konstitučními příznaky. Diagnostika se opírá o morfologické a histologické zhodnocení kostní dřeně. Pacienti jsou na základě diagnostických nálezů a symptomatologie klasifikováni dle WHO a ICC klasifikace, od kterých se odvíjí typ onemocnění a následná terapie, která je přísně individualizovaná a zahrnuje symptomatickou, cílenou i cytoredukční terapii. Vzhledem k širokému spektru symptomů může pacient se SM kromě hematologů a alergologů navštívit ambulance specialistů většiny interních oborů. Proto je nutné, aby se tato diagnóza dostala do širšího povědomí lékařské společnosti. Nízká informovanost vede k oddálení diagnózy, dispenzarizace a případné terapie, což může u některých pacientů se sklonem k vážným alergickým až anafylaktickým reakcím vést v krajních případech k opakovanému výskytu život ohrožujících situací.
Systemic mastocytosis (SM) is a disease characterized by the proliferation of clonal mast cells. SM biologically include a wide spectrum, ranging from relatively benign indolent forms to mast cell leukemia. The clinical presentation varies from nearly asymptomatic forms, through various degrees of mediator syndrome, to a neoplastic syndrome associated with hepatosplenomegaly, lymphadenopathy, and constitutional symptoms. Diagnosis relies on morphological and histological evaluation of the bone marrow. Patients are classified based on diagnostic findings and symptomatology according to the WHO and ICC classifications, which determine the type of disease and subsequent therapy, which is strictly individualized and includes symptomatic, targeted, and cytoreductive therapy. Given the wide spectrum of symptoms, patients with SM may visit specialists in most internal medicine departments in addition to hematologists and allergologists. Raising awareness of this diagnosis within the medical community is crucial. Low awareness leads to delayed diagnosis and undertreatment, posing risks of life-threatening situations in patients liable to severe allergic reactions.
Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.
