Further evidence for the clonal nature of the idiopathic hypereosinophilic syndrome: complete haematological and cytogenetic remission induced by interferon‐alpha in a case with a unique chromosomal abnormality

Abstract

A 49-year-old man with the idiopathic hypereosinophilic syndrome (HES) and a unique chromosomal abnormality 46,XY,t(5;9)(q32;q33) is reported. Complete cytogenetic remission was induced by interferon alpha-2b (IFN-alpha). The beneficial action of IFN-alpha in different stem-cell disorders such as CML, HES, multiple myeloma and solid tumours such as hypernephroma or malignant melanoma suggests a common regulatory effect possibly by immunomodulation or other (immune-mediated) mechanisms, but the exact pathophysiological mechanisms remain hypothetic and unresolved. Since it has been known for some years that the genes encoding for GM-CSF, IL-3 and IL-5 reside on the long arm of chromosome 5, it could be possible that the chromosomal translocation in our patient resulted in excess production of these cytokines, hence causing the hypereosinophilia. This case report and the results obtained from the literature review support the growing body of evidence that IFN-alpha has a major place in the long-term treatment of HES, especially in those cases resistant to conventional treatment, with cytogenetic abnormalities, or presenting as a myeloproliferative variant of HES. In those cases IFN-alpha results in lower morbidity, lower mortality and long-term survival.

Hypereosinophilic Syndrome and Clonal Eosinophilia: Point-of-Care Diagnostic Algorithm and Treatment Update

“…42,43 Drug doses in this instance have usually been higher (400 mg/d), and currently it is unknown if lower doses would have the same effect. As was the case with FIP1L1-PDG-FRA-positive clonal eosinophilia, 27,39 patients with PDG-FRB rearrangements, possibly due to 5q31-33 cytogenetic abnormalities, might achieve clinical and cytogenetic remissions with interferon alfa therapy, [44][45][46] an observation that supports the use of interferon in imatinib mesylateresistant or -intolerant cases.…”

Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias

“…It should be noted that the high autofluorescence of the eosinophilic granules precluded evaluation of a proportion of mature eosinophils. In cases [13][14][15][16][17], that were FIP1L1-PDGFRA (À), the loss of one 3H20 signal was observed in only 0.5-1.5% of the nuclei, defining the background of the assay. In cases 4 and 8, with normal karyotype and available metaphase spreads, a three-color FISH assay with the additional 120K16 clone labelled with DEAC (shown as yellow, Figure 2c and d) was performed.…”

“…8 Case 16 has also been published previously. 13 Cytogenetic analysis was performed after unstimulated shortterm culture of bone marrow using standard methods. In all, 10 R-banded metaphase spreads were analyzed per case.…”

The FIP1L1-PDGFRα fusion tyrosine kinase in hypereosinophilic syndrome and chronic eosinophilic leukemia: implications for diagnosis, classification, and management

“…138,139 Interferon-␣ (IFN-␣) can elicit long-term hematologic and cytogenetic responses in HES and CEL patients resistant to other therapies, including prednisone and hydroxyurea. 109,[140][141][142][143][144][145] Some have advocated its use as initial therapy for these diseases. 144 Remissions have been associated with improvement in clinical symptoms and organ disease, including hepatosplenomegaly, 140,144 cardiac and thromboembolic complications, 109,141 mucosal ulcers, 143 and skin involvement.…”