Eosinophilia, for which a cause is ascertained, can be clonal or reactive. Primary Clonal Eosinophilic Disorders
The primary clonal eosinophilic disorders include eosinophilic leukemias of exclusively eosinophilic lineage, for example, acute eosinophilic leukemia and chronic eosinophilic leukemia (also known as myeloproliferative variant of idiopathic hyper-eosinophilic syndrome). The following karyotypic abnormalities associated with chronic eosinophilic leukemia have been reported: The majority of patients have t (5 ; 12) (q33 : p 13). Sporadic patients have trisomy 8, i (17q), t (5 ;12) (q 31: q13), t (1; 5) (q 23: q 33), t (2; 5) (p 13: q 35), t (5; 9) (q 32: q33), t (5 ; 16) (q 33 : p 13), trisomy 10, 17q+, 15q-, -7,t (7; 12) (q11: p11), or t (4;16) (q11 or 12: p13).
A special variant of HES with a fusion gene FIP1L1-PDGFRA occurring as a result of interstitial deletion on chromosome 4q12 has recently been described. The fusion gene makes an activated tyrosine kinase, which results in a myeloproliferative variant of HES. It is characterized by increased levels of tryptase, increased atypical mast cells in bone marrow, and tissue fibrosis (myelofibrosis, endomyocardial fibrosis, pulmonary fibrosis). They respond well to imatinib mesylate treatment, which targets the fusion tyrosine kinase. Some patients with the FIP1L1-PDGFRA fusion gene may not have the classic characteristics of a myeloproliferative variant of HES and also respond well to imatinib. Some patients with HES may not have the FIP1L1-PDGFRA fusion gene and still respond to imatinib.
Secondary clonal involvement of eosinophil lineage can occur in myeloproliferative disorders of stem cell origin, for example, Ph1-positive chronic myeloid leukemia. Eosinophilia is observed less commonly in polycythemia vera, myelofibrosis, and essential thrombocythemia.
In noneosinophilic clonal disorders, clonal cells release eosinopoietic cytokines and, thus, are associated with eosinophilia. These noneosinophilic clonal disorders
Treatment of reactive or nonclonal eosinophilia: Treat the underlying cause, e.g., treatment of parasitic infections with appropriate antiparasitic drugs Treatment of clonal disease: Myeloid clonal disease: Treat with appropriate chemotherapy
± hematopoietic stem cell transplantation. Lymphoid malignancies: Treat with appropriate chemotherapy.
CD3-, CD4+ Lymphoid clonal disease with high levels of IL-5, usually associated with dermatologic manifestations: Treat with cyclosporine A, glucocorticoids or 2CDA. CD3+, CD4-, CD8- Lymphoid clonal induced eosinophilia with high levels of IL-5 and usually associated with dermatologic manifestations: Treat with glucocorticoids, cyclosporine A.
Treatment of HES caused by interstitial deletion of 4q12 resulting in a fusion gene FIP1L1-PDGFRA: Imatinib mesylate, adult dose: 400 mg day. Pediatric dose: not established.
Treatment of idiopathic HES: Glucocorticoids, hydroxyurea, a-interferon, vincristine, thioguanine, or etoposide. Use these agents sequentially and if the response is unsatisfactory then treat with imatinib mesylate at doses of 100-200 mg/day (of interest is that patients with normal serum interleukin-5 values respond to imatinib, but not the ones with high values). During acute life-threatening presentation of HES, high-dose 10-20 mg/kg of Solu-Medrol (methylprednisolone) may be required but usually 1-2 mg/kg of prednisone may be sufficient.
Treatment with allogeneic hematopoietic stem cell transplantation is reserved for patients with HES refractory to above-mentioned therapies. Treatment of patients with idiopathic HES but without organ involvement: None.
Treatment is not necessary, but continuous periodic monitoring for organ involvement and emergence of clonality is warranted. Also, continue search for rare reactive causes of eosinophilia.
The following eosinophilic disorders with single-organ involvement may progress into HES:
Gleich syndrome (episodic eosinophilia with angioedema) Loeffler syndrome
Schulman syndrome (eosinophilic fascitis) Well syndrome (eosinophilic cellulitis) Parasitic infections with eosinophilia.
Note:Doses of some of the drugs: thioguanine, 40-60 mg/m2/day orally. Vincristine, 1.5 mg/m2/week IV. Etoposide, 60-100 mg/m2/day for 3-5 days IV every 3-6 weeks. Hydroxyurea, 10-20 mg/kg/day orally. Cyclosporine 6 mg/kg/day orally (trough level, 100-200 |g/L). a-Interferon, 5 x 106 units/m2/day SC or IM.
may be lymphoid or myeloid in their clonality. Lymphoid clonal disorders associated with eosinophilia include dermatologic patients with abnormal clones of T cells producing interleukin-5, patients with acute lymphoblastic leukemia, and T-lymphoblastic lymphoma. Myeloid clonal disorders associated with eosinophilia include myelodysplastic syndromes, acute myeloid leukemia with chromosome 16 abnormality, the 8p myeloproliferative syndrome, myelodysplastic syndromes, and systemic mastocytosis. The following cytogenetic abnormalities associated with acute myeloid leukemia with eosinophilia have been reported: inv (16) (p13: q22), t(16:16)(p 13: q22), t(5; 16) (q33:q22), and monosomy 7. Reactive or nonclonal eosinophilic conditions are listed in Table 9-12.
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