Eosinophilia often occurs as a secondary process due to
Eosinophilia often occurs as a secondary process due to parasitic infections, allergy, dhpg disease, malignancy, or drug reactions. When secondary causes of eosinophilia are excluded, one must consider HES, which is defined as a peripheral eosinophil count of greater than 1.5×109/L on at least 2 occasions and the absence of secondary causes. The syndrome includes several variants, including myeloproliferative HES, lymphocytic HES, and organ-limited eosinophilic disorders, some of which are overlapping. The myeloproliferative variant can display similar features as the classical MPN, including organomegaly, marrow fibrosis, clonality, increased vitamin B12 levels, thrombotic tendencies, and AML transformation. However, this group of illnesses is typically clinically and molecularly distinct from the classical MPN.
A novel fusion tyrosine kinase, FIP1L1-PDGFRα, was identified as the most common genetic abnormality in the myeloproliferative forms of HES, and this form is responsive to imatinib. Our patient was tested for the FIP1L1-PDGFRα mutation as well as other less common mutations, none of which were present. Although imatinib can successfully inhibit the constitutively active tyrosine kinase created by the FIP1L1-PDGFRα rearrangement and lead to a complete hematologic response in nearly 100% of patients harboring this specific mutation, imatinib has also been used in cases of HES without the FIP1L1-PDGFRα mutation with limited success. Due to the critical illness of our patient, severe end-organ damage from eosinophilia, and lack of significant response to high-dose steroids, our patient was treated with imatinib, despite her negative FIP1L1-PDGFRα status. She had a dramatic response to imatinib 100mg daily, and her eosinophil counts were suppressed 6 months after diagnosis of HES with imatinib, which had been reduced to weekly dosing due to cytopenias. Her prognosis is still guarded given the poor outcomes associated with her underlying post-PVMF.
The mechanism accounting for our patient\'s hypereosinophilia is unexplained, as molecular testing did not reveal a characteristic abnormality as seen in myeloproliferative forms of HES. In part due to an inaspirable bone marrow, cytogenetics could not be obtained, impairing recognition of clonal evolution, such as the t(6;10)(q27;q11) in a previously described case or a mutation of FGFR1, which is associated with the 8p11 myeloproliferative syndrome that frequently presents with eosinophilia. Interestingly, JAK2, has also recently been identified as a mediator of eosinophil growth that is activated by the FIP1L1-PDGFRα fusion gene in that form of myeloproliferative HES. It is unclear whether the hypereosinophilia was an isolated secondary process in our patient\'s case, but we suspect that it was a consequence of clonal evolution of her underlying MPN, with aberrant, imatinib-sensitive tyrosine kinase activity leading to eosinophil proliferation.
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is an open access, international journal which delivers timely information online to all health care professionals involved in basic and/or applied clinical research in leukemias, lymphomas, multiple myeloma and other hematologic malignancies. It does this by rapidly publishing a range of peer-reviewed short form papers, including brief communications, case reports, letters to the Editors, images, and debate articles. The Editors encourage the submission of articles relevant to normal and leukemic hemopoiesis, biochemistry, cell biology, immunology and molecular biology as well as epidemiologic and clinical studies. \' coverage encompasses the application of oncogenes, genomics (gene expression profiles and microRNAs), proteomics, growth factors, cell markers, cell cycle and differentiation agents, novel therapeutics and clinical trials in both the acute and chronic leukemias as well as the myelodysplastic syndromes. In addition articles are solicited on the rapidly growing specialty of marrow or stem cell reconstitution after high dose therapy with curative attempt in patients with a wide range of neoplasms.