Table 1.

Subtypes of hypereosinophilic syndromes and treatment.

Category	Variant	Clinical and laboratory characteristics	Pathophysiology	First line therapies	Second line therapies
Primary	Chronic eosinophilic leukemia, not otherwise specified	Circulating myeloblasts and/or clonal cytogenetic abnormalities, cytopenias, constitutional symptoms, hepatomegaly, splenomegaly, may accelerate or transform into acute myeloid leukemia	Various mutations, including those involving KIT, JAK2 V617F, ETV6-PDGFRB, or ETV6-ABL1	Imatinib for ETV6-PDGFRB or ETV6-ABL1 mutations	Chemotherapy; hematopoietic stem cell transplant
	Myeloid variant (M-HES)	Circulating leukocyte precursors and/or clonal cytogenetic abnormalities, cytopenias, hepatomegaly, splenomegaly, elevated serum B12 and tryptase levels (typically in FIP1L1-PDGFRA fusion only)	FIP1L1-PDGFRA fusion (most frequent genetic abnormality observed in M-HES)	Imatinib, often as little as 100 mg daily or less	Other tyrosine kinase inhibitors
			PDGFRA or PDGFRB rearrangement (nearly exclusive to males)	Imatinib	Other tyrosine kinase inhibitors; hydroxyurea
			FGFR1 rearrangement	Ponatinib; Midostaurin	Other tyrosine kinase inhibitors
			JAK2 point mutation or fusion	Ruxolitinib	Other kinase inhibitors
	Familial HES	HE is present at birth. Patients are often asymptomatic, but may rarely progress to end-organ damage	Unknown. Mutations have been mapped to 5q31–33 with autosomal dominant transmission.	Observation	GCs if necessary
Secondary	T cell lymphocytic variant (L-HES)	Typically with pronounced dermatologic findings and abnormal T cell immunophenotyping, may progress to T cell lymphoma	Clonal lymphoproliferative disorder, clones produce excess IL-5	GCs	IFN-α; JAK inhibitors; immunosuppressive agents; anti-eosinophil biologics

HES: hypereosinophilic syndromes; PDGFRB: platelet-derived growth factor receptor beta; FGFR1: fibroblast growth factor receptor 1; GC: glucocorticoid; IFN-α: interferon alpha; JAK2: Janus kinase 2; FIP1L1: Fip1-like1; PDGFRA: platelet-derived growth factor receptor alpha; L-HES: lymphocytic variant HES; IL-5: interleukin-5.

Modified from: Dispenza MC, Bochner BS. Diagnosis and novel approaches to the treatment of hypereosinophilic syndromes. Curr Hematol Malig Rep. 2018; 13: 191–201.⁷²