Eosinophilia and Hypereosinophilic Syndrome, Mastocytosis, and Myelodysplastic Syndromes
Hematology · Hematopoietic Stem Cells and Their Disorders 🎯 Practice these cards
Eosinophilia is defined as an absolute eosinophil count above ____/µL; because most cases are secondary, the first diagnostic step is to look for a ____ explanation rather than a primary hematologic disease.
Eosinophilia is defined as an absolute eosinophil count above 500/µL (0.5 × 10^9/L). In most patients the elevation is mild, transient, and secondary to another process, so the first task is to look for a reactive explanation rather than a primary hematologic disease.
In the CHINA mnemonic for eosinophilia, H stands for ____ infection, and the most common neoplastic association is ____.
CHINA summarizes the major causes of eosinophilia: Collagen vascular disease (classically eosinophilic granulomatosis with polyangiitis), Helminthic (parasitic worm) infection such as Strongyloides, Idiopathic hypereosinophilic syndrome, Neoplasia (myeloproliferative neoplasms, AML, lymphomas — the most common neoplastic association — and some solid tumors), and Allergy/atopy/asthma/drug reactions.
Hypereosinophilic syndrome is defined by a persistent eosinophil count >____/µL together with ____ directly mediated by eosinophils.
Hypereosinophilic syndrome (HES) is defined by a persistently elevated eosinophil count >1500/µL (1.5 × 10^9/L) together with organ damage directly mediated by eosinophils; dermatologic, pulmonary, and gastrointestinal complications are the most commonly seen, but virtually any organ can be affected.
Because eosinophilic ____ is a major cause of morbidity and mortality in HES, an echocardiogram and serum ____ belong in the initial evaluation.
Although infrequent, eosinophilic myocarditis is a major cause of morbidity and mortality in HES; an echocardiogram and serum troponin belong in the initial evaluation. Troponin elevation correlates with cardiomyopathy, and characteristic echo findings include apical ventricular thrombus, endocardial thickening, valve abnormalities, a dilated left ventricle, and pericardial effusion.
The prototype driver of primary HES is the karyotypically occult ____ fusion on chromosome 4q12, and affected patients are treated with low-dose ____.
Primary HES is a rare clonal myeloproliferative neoplasm often driven by PDGFRA or PDGFRB fusions — the prototype being the karyotypically occult FIP1L1::PDGFRA deletion on chromosome 4q12 — and these patients respond remarkably well to low-dose imatinib, with essentially all achieving complete hematologic responses. An elevated serum tryptase in eosinophilia should prompt molecular testing for FIP1L1::PDGFRA.
Before giving glucocorticoids for HES, active ____ infection must be ruled out, because steroids can trigger fatal ____ and dissemination.
Before giving glucocorticoids for HES, active Strongyloides infection must be ruled out, because steroids can trigger hyperinfection and dissemination of strongyloidiasis, which can be fatal.
____, an anti-____ monoclonal antibody, was FDA approved for HES in September 2020 and remains the only approved biologic for HES.
Mepolizumab, an anti-IL-5 monoclonal antibody, was FDA approved for HES in September 2020 and significantly reduces disease flares; it remains the only approved biologic for HES so far. For idiopathic HES, glucocorticoids (prednisone 1 mg/kg/day tapered over 2-3 months) are the cornerstone, with hydroxyurea or interferon-alpha as steroid-sparing agents.
More than ____% of patients with systemic mastocytosis carry an activating ____ mutation, classically D816V.
More than 95% of patients with systemic mastocytosis carry an activating KIT mutation, classically KIT D816V. Most adult disease is indolent SM (>70% of cases) with normal life expectancy; progression from indolent to advanced forms is uncommon (~5% lifetime risk).
The major criterion for systemic mastocytosis is multifocal dense aggregates of ____ or more mast cells, and a basal serum tryptase >____ ng/mL is a minor criterion.
The major diagnostic criterion for systemic mastocytosis is multifocal dense aggregates of 15 or more mast cells in tissue (usually bone marrow); minor criteria include >25% spindle-shaped mast cells, aberrant CD25/CD2/CD30 expression, an activating KIT mutation, and a basal serum tryptase >20 ng/mL. One major plus one minor criterion, or three minor criteria, establishes the diagnosis.
Imatinib is ineffective in most systemic mastocytosis because the ____ mutation mediates resistance.
Imatinib is highly effective in PDGFR-rearranged eosinophilic neoplasms but ineffective in most systemic mastocytosis, because the KIT D816V mutation mediates resistance. Do not extrapolate the imatinib responsiveness of one clonal mast cell/eosinophil disorder to another.
In May 2023 ____, a KIT D816V-directed inhibitor, became the first FDA-approved therapy for ____ systemic mastocytosis, based on the PIONEER trial.
In May 2023 avapritinib (25 mg daily) became the first FDA-approved therapy for indolent systemic mastocytosis, based on the placebo-controlled PIONEER trial: significant improvements in total symptom score, mast cell burden and tryptase, and quality of life, deepening through 48 weeks. ISM management is shifting from purely supportive care to disease-modifying, KIT D816V-directed therapy.
Therapy-related MDS linked to alkylating agents typically appears after a ____-year latency, whereas topoisomerase II inhibitor-related disease has a latency of about ____ years.
Therapy-related MDS linked to alkylating agents typically appears after a 5-7 year latency, whereas topoisomerase II inhibitor-related disease has a latency of about 2 years. In patients younger than 40, constitutional marrow failure syndromes and germline predisposition (GATA2, RUNX1, telomere biology disorders) should be considered.
MDS with excess blasts-2 is defined by ____%-____% marrow blasts (or Auer rods), and the historical boundary separating MDS from AML is ____% blasts.
In the 2016 WHO classification, MDS with excess blasts-1 has 5%-9% marrow blasts and MDS with excess blasts-2 has 10%-19% blasts or Auer rods; historically, the boundary separating MDS from AML has been set at 20% blasts in the marrow. The ICC 2022 introduces an MDS/AML category (10%-19% blasts), emphasizing the continuum.
Most patients with MDS die from complications of ____ rather than leukemic transformation; low-risk disease may have a median survival approaching ____ years.
Most MDS patients die from complications of pancytopenia rather than from leukemic transformation. Patients with low-risk disease may have a median survival approaching 9 years, whereas those with >10% blasts, severe pancytopenias (Hb <8 g/dL, platelets <50,000/µL, ANC <800/µL), and adverse cytogenetics survive less than 1 year.
The IPSS-M score adds somatic mutations in ____ genes to the IPSS-R variables and reclassifies nearly ____ of patients relative to IPSS-R, mostly by upstaging.
The IPSS-Molecular (IPSS-M) score adds somatic mutations in 31 genes (including SF3B1, multi-hit TP53, RUNX1, and ASXL1) to the IPSS-R clinical and cytogenetic variables, defining six risk categories and reclassifying nearly half of patients relative to IPSS-R — mostly by upstaging. It has become the preferred prognostic tool in current practice.
The only cure for MDS is allogeneic ____; for higher-risk non-transplant candidates, the hypomethylating agent ____ (with decitabine) decreases transfusion dependence and AML conversion risk.
Allogeneic hematopoietic stem cell transplantation is the only cure for MDS, but it is too toxic for most older adult patients. For higher-risk non-transplant candidates, the hypomethylating agents azacitidine and decitabine improve blood counts, decrease transfusion dependence, and lower the risk of conversion to AML; azacitidine improves survival compared with supportive care alone, and responses require at least four cycles to assess.
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