Eosinophilia and Hypereosinophilic Syndrome, Mastocytosis, and Myelodysplastic Syndromes
Hematology · Hematopoietic Stem Cells and Their Disorders · study mode — pick an answer, then reveal.
Question · easy
A 45-year-old man is found to have a persistently elevated eosinophil count on serial CBCs over 8 weeks. Which combination of findings is required to establish a diagnosis of hypereosinophilic syndrome (HES)?
HES is not defined by the eosinophil count alone. It requires BOTH a persistently elevated absolute eosinophil count >1500/µL (1.5 × 10^9/L) AND organ damage directly mediated by eosinophils (skin, lung, and GI tract most commonly, but also heart, nervous system, and thromboembolic events). Count >500/µL defines simple eosinophilia, which is most often reactive (CHINA mnemonic: Collagen vascular disease, Helminthic infection, Idiopathic HES, Neoplasia, Allergy/drug). A single elevated value lacks the persistence criterion, and elevated tryptase suggests mast cell involvement rather than defining HES.
MKSAP 19 B.4 Ch.2; Harrison's 22e Ch.115
Question · medium
A 58-year-old woman with flushing, pruritus, and peptic symptoms is diagnosed with indolent systemic mastocytosis confirmed by bone marrow biopsy. Her molecular studies show KIT D816V. Her physician considers starting imatinib, reasoning that it works well in related clonal eosinophilic disorders. Why is this reasoning flawed?
This is the classic 'imatinib trap': imatinib produces remarkable responses in primary HES driven by PDGFRA/PDGFRB fusions (e.g., FIP1L1::PDGFRA), but it does NOT work in most systemic mastocytosis because the activating KIT D816V mutation (>95% of SM cases) confers imatinib resistance. Responsiveness in one clonal mast cell/eosinophil disorder cannot be extrapolated to another. KIT D816V-directed therapy (e.g., avapritinib, approved for indolent SM in 2023) or cytoreductive agents like midostaurin and cladribine are the appropriate options for advanced disease, while indolent SM is managed symptomatically.
A 72-year-old man with low-risk MDS and an isolated del(5q) abnormality has become transfusion dependent despite an erythropoiesis-stimulating agent. Which therapy is most likely to restore transfusion independence, often with cytogenetic normalization?
Patients with low-risk MDS and isolated del(5q) who are transfusion dependent respond strikingly to lenalidomide: a high proportion achieve transfusion independence, often with cytogenetic normalization, though myelosuppression and thromboembolic risk require monitoring. Transplantation is the only cure for MDS but is too toxic to justify in low-risk disease and reserved for selected poor-prognosis patients. Glucocorticoids treat idiopathic HES, not MDS. Venetoclax plus azacitidine is approved for AML but is NOT approved in MDS.
MKSAP 19 B.4 Ch.2; Harrison's 22e Ch.107
Question · hard
A 34-year-old man who grew up in the southeastern United States presents with fatigue, cough, and persistent eosinophilia of 2800/µL. Workup is negative for clonal markers, and idiopathic hypereosinophilic syndrome is suspected. The team plans to start prednisone 1 mg/kg/day. What is the most important step BEFORE initiating glucocorticoids?
Before giving glucocorticoids for suspected HES, active Strongyloides infection must be excluded. Steroids can trigger hyperinfection syndrome and disseminated strongyloidiasis, which can be fatal — and this patient has epidemiologic risk (southeastern United States is endemic). This is the CHINA mnemonic's 'H' (helminthic infection) in action: parasitic causes must be excluded before labeling HES idiopathic. Echocardiography and troponin do belong in the initial HES evaluation (eosinophilic myocarditis is a major cause of morbidity), but they do not gate steroid therapy. Empiric imatinib is reserved for PDGFR-rearranged disease, and mepolizumab is for confirmed idiopathic HES after workup.
MKSAP 19 B.4 Ch.2; Harrison's 22e Ch.115
Question · hard
A 68-year-old woman with newly diagnosed lower-risk MDS has transfusion-dependent anemia and has never received an erythropoiesis-stimulating agent. Based on the COMMANDS trial, which statement best supports choosing luspatercept as first-line therapy?
In the phase 3 COMMANDS trial in ESA-naive, transfusion-dependent lower-risk MDS, luspatercept was superior to epoetin alfa for achieving red-cell transfusion independence of 12 weeks or longer (~58% vs ~31%), with benefit in both SF3B1-mutated and non-mutated subgroups and durable independence beyond 18 months — making it a preferred first-line option. The telomerase-inhibitor description (option B) is imetelstat, approved in June 2024 after ESA failure/intolerance (IMerge trial). No drug cures MDS — only allogeneic transplantation does — and option D misstates the subgroup data.
Platzbecker U, et al. Lancet 2023 (COMMANDS); Platzbecker U, et al. Lancet 2024 (IMerge); Harrison's 22e Ch.107