Pediatric Hypereosinophilic Syndrome Medication

Updated: Aug 02, 2018
  • Author: Bruce M Rothschild, MD; Chief Editor: Harumi Jyonouchi, MD  more...
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Medication

Medication Summary

No therapy is indicated in the absence of organ damage. Treatment is directed at organ system involvement and at reducing the eosinophil load and perhaps the eosinophil effect.

A small experimental study found that alemtuzumab was helpful in advanced hypereosinophilic syndrome refractory to other standard therapies. Escalating doses of 5 mg, 10 mg, and 30 mg IV on days 1-3, and then at tolerated dose 3 times per week for 3 weeks, were suggested. If a full response is seen, consider weekly administration. The authors suggest clinical evaluation of alemtuzumab in a larger clinical trial is warranted. [13]

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Corticosteroids

Class Summary

These agents interfere with eosinophilopoiesis by antagonizing IL-5, IL-3, and granulocyte/monocyte cell–stimulating factor. They also suppress eosinophilia; however, discontinue corticosteroids if eosinophilia is not suppressed. Response to steroids is considered a good prognostic indicator.

Prednisone (Deltasone, Meticorten, Orasone, Sterapred)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.

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Immunosuppressant and immunomodulator agents

Class Summary

These drugs are used to inhibit DNA synthesis, but only case reports of their effectiveness are available.

Hydroxyurea (Hydrea)

Interferes with DNA synthesis. Used to reduce total leukocyte count to < 10,000/µL. Requires 7-14 d for effectiveness.

Vincristine (Oncovin)

Used to reduce total leukocyte count to < 10,000/µL. Effective in 1-3 d and spares bone marrow toxicity but may cause paresthesias.

Cyclophosphamide (Cytoxan)

Used to reduce total leukocyte count to < 10,000/µL.

Busulfan (Myleran)

Used to reduce total leukocyte count to < 10,000/µL.

Methotrexate (Rheumatrex)

Used to reduce total leukocyte count to < 10,000/µL.

Chlorambucil (Leukeran)

Used to reduce total leukocyte count to < 10,000/µL.

Etoposide (VP16-213, VePesid)

Podophyllotoxin derivative that acts as topoisomerase II inhibitor to cause DNA damage.

Interferon alfa 2b (Intron A)

Empirically applied to many diseases as immunomodulator. Acts at biologically active sites in eosinophil action.

Cyclosporine (Sandimmune, Neoral)

Inhibits T-cell clonal release of eosinophilopoietin cytokines.

Sorafenib (Nexavar)

Multikinase inhibitor that targets serine/threonine and tyrosine receptor kinases in both the tumor cell and the tumor vasculature. Targets kinases involved in tumor cell proliferation and angiogenesis, thereby decreasing tumor cell proliferation. These kinases include RAF kinase, VEGFR-2, VEGFR-3, PDGFR-beta, KIT, and FLT-3.

Imatinib mesylate (Gleevec)

Specifically designed to inhibit tyrosine kinase activity of the bcr-abl kinase in Ph+ leukemic chronic myeloid leukemia (CML) cell lines. Well absorbed after PO administration, with maximum concentrations achieved within 2-4 hours. Elimination is primarily in feces in form of metabolites. FDA-approved for chronic hypereosinophilic syndrome in adults. Also indicated to treat pediatric patients with Ph+ chronic phase CML whose disease has recurred after stem cell transplant, or have demonstrated interferon alpha resistance.  In patients with confirmed formation of FIP1L1-PDGFRA fusion gene, imatinib is expected to be effective by blocking tyrosine kinase activity of PDGFRA; this fusion gene induced hyperactivity of tyrosine kinase of PDGFRA.

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Anti-inflammatory agents

Class Summary

Dapsone is a sulfone antimicrobial. Its anti-inflammatory action, which enables its use for dermatologic conditions, is not fully understood but does not appear to be associated with its antibacterial action.

Dapsone (Avlosulfon)

Sulfone specifically useful for skin involvement.

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Anticoagulant and antiplatelet agents

Class Summary

These agents are used in an effort to reduce frequency of thrombotic events. Warfarin and aspirin have well-established roles in preventing thrombosis. Warfarin acts as an anticoagulant by antagonizing vitamin K in its role as a cofactor in the carboxylation process of coagulation factors II, VII, IX, and X. Aspirin possess antiplatelet ability by permanently inactivating cyclooxygenase (COX) activity of prostaglandin synthase-1 and prostaglandin synthase-2 (ie, COX-1 and COX-2).

Thromboxane A2 (TXA2) induces platelet aggregation and vasoconstriction. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit TXA2 by reversible inhibition of COX-1. The level of reversible inhibition provided by NSAIDS may be inadequate to effectively block platelet aggregation in vivo. However, the NSAID indobufen, which is not available in the United States, is a potent inhibitor and has biochemical activity comparable to aspirin. Further investigation of effective antiplatelet drugs is essential to overcome obstacles associated with aspirin (eg, toxicity, resistance).

Warfarin (Coumadin)

Used to achieve sufficient anticoagulation to prevent thrombotic events. Interferes with hepatic synthesis of vitamin K–dependent coagulation factors. Used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. Adjust dose to maintain INR of 2-3 in absence of associated anticardiolipin syndrome.

Aspirin (Anacin, Ascriptin, Bayer)

Inhibits prostaglandin synthesis, preventing formation of platelet-aggregating TXA2. May be used in low dose to inhibit platelet aggregation and improve complications of venous stases and thrombosis.

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Interleukin inhibitor

Class Summary

Results from a Phase III study demonstrate significantly more patients who received mepolizumab for treatment of hypereosinophilic syndrome were able to maintain disease control with reduced corticosteroid use (84% vs 43%, p< 0.001). [14]

Mepolizumab

Humanized anti-interleukin-5 monoclonal immunoglobulin G1 antibody. Pending FDA approval for severe eosinophilic asthma. 

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