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Treatment of HES

Treatment of Hypereosinophilic Syndrome
Treatment goals include decreasing blood eosinophil numbers, preventing organ damage,
and slowing disease progression. Treatments vary based on organs involved and disease
severity, as well as on the presence of other medical problems a patient may have. Therapy
for hypereosinophilic syndrome requires careful discussion with your health care providers
regarding the risks and benefits of the treatment for your specific HES- related organ
involvement.

Systemic steroids are often needed to treat HES with organ involvement or with systemic
symptoms, like severe rash, fluid retention, and similar. Steroids are medications that fight
(suppress) many types of inflammation. They are not specific for suppressing eosinophils,
although eosinophils are particularly sensitive to them. Systemic steroids, those that are
absorbed into the bloodstream (oral or IV), are very effective for treating a number of
eosinophilic disorders. Steroids are very effective for controlling eosinophil numbers in blood
and most HES patients can be maintained on oral steroid medication (called prednisone) for
long period of time with good control of the disease. However, the blood eosinophils and
disease symptoms generally return once steroids have been stopped. Long-term steroid use
(especially when used in high doses) has, unfortunately, been associated with certain side
effects. Serious side effects can include osteoporosis (brittle bones from bone loss),
infections, adrenal insufficiency (body becomes unable to properly respond to illness or
stress), avascular necrosis (collapse of the bones in a joint, usually the hip), and stunted
growth. Common side effects may include fluid retention (swelling), increased appetite,
“moon-face”, and irritability.

Interferon alpha (IFNa) is used for a variety of diseases including infections (like hepatitis)
and malignancies (like certain types of leukemia). IFNa has been shown to be effective in
HES by suppressing the symptoms related to the disease. Toxicity, however, is a major
obstacle to the use of this therapy. IFNa is commonly injected into the fatty tissue under the
skin 3-5 times a week. Upon the initiation of therapy most patients experience influenza-like
symptoms such as fever, chills, muscle aches, headaches, and joint pain. Other side effects
of IFNa are low blood counts and elevated liver enzymes that require careful monitoring.
These side effects usually lessen over time, but other toxicities can manifest themselves in
various forms after long-term therapy. Overall experience with IFNa in myeloproliferative
neoplasms is that about 25-30% of patients require discontinuation of therapy due to side
effects. New long-acting forms of IFNa (pegylated interferons) have been developed over last
few years and are now approved as therapy for hepatitis. These medications are
administered only once a week and may, therefore, be better tolerated.

Cyclosporine is a potent medication that suppresses the immune system and it is used
primarily to prevent organ rejection in people who have had organ transplants. In some
patients with HES there might be evidence that the immune cells have a role in supporting
the diseases existence (so called T cells) and cyclosporine may have a role as therapy in
such cases.

Anti-neoplastic agents (chemotherapy) provide an alternative approach to therapy of
advanced cases of HES. These are chemotherapeutic agents that may control the disease.
They are used to treat many malignancies and are not specific for eosinophilic disorders.
They are potent medications that kill cells that grow the fastest (eosinophils in HES) but may
potentially have harmful side effects and are reserved only for more severe cases. Careful
monitoring while taking these medications is essential. Chemotherapeutic agents that have
been used in HES include: Hydroxyurea, Methotrexate, Etoposide, Cyclophosphamide,
Vincristine, and Cladribine.

Gleevec (Imatinib Mesylate) is a tyrosine kinase inhibitor. As a result of cell growth
research, scientists have been able to develop a group of therapeutic agents known as
tyrosine kinase inhibitors (TKI). Tyrosine kinases are enzymes in the cells with a variety of
functions. By blocking the ability of tyrosine kinases to function, TKI provide a valuable tool
for controlling malignant cell growth. Several years ago a discovery was made in some
patients with HES of a genetic abnormality involving tyrosine kinase called PDGFRα. In thes
cases it seems that PDGFRα abnormality is responsible for disease existence. Gleevec is
TKI that inhibits PDGFRα and may eliminate the disease in HES patients with PDGFRα
abnormality. Genetic testing for PDGFRα abnormality is usually part of the bone marrow
evaluation and can help determine if Gleevec is best first therapy. Not all patients with HES
will respond to Gleevec as about 10-20% of patients may have PDGFRα. In HES patients
without PDGFRα abnormality Gleevec can be tried as therapy but it is unlikely to eliminate
the disease; it may help control the disease signs and symptoms for a period of time.

New therapies for HES
For patients who are refractory to conventional therapies, use of monoclonal antibody
therapy (medications that selectively bind to specific proteins) should be considered. Two
drugs are currently available: mepolizumab that targets interleukin-5, a cytokine in blood that
is recognized as very important protein that governs eosinophil growth, and alemtuzumab
that targets the CD52 protein expressed on the surface of eosinophils (its function not yet
known). Mepolizumab, therefore, by blocking interleukin-5 eliminates a cytokine from blood
that provides signal for eosinophil growth. Alemtuzumab, on the other hand, by binding to
CD52 kills the eosinophil. Mepolizumab is not approved therapy yet and is currently available
in a compassionate-use program (http://clinicaltrials.gov) sponsored by GlaxoSmithKline, for
patients with life-threatening HES that is not responding to usual therapy. Alemtuzumab is
currently approved by the Food and Drug Administration for use in B-cell chronic lymphocytic
leukemia.

References
1. Eosinophilic myeloid disorders: new classification and novel therapeutic strategies.
Gotlib J. Curr Opin Hematol. 2010 Jan 11. [Epub ahead of print]
2. Hypereosinophilic Syndrome and Clonal Eosinophilia: Point-of-Care Diagnostic
Algorithm and Treatment Update. Tefferi A, Gotlib J, Pardanani A. Mayo Clin Proc.
2010 Feb;85(2):158-64.
3. Recent breakthroughs in the understanding and management of chronic eosinophilic
leukemia. Lierman E, Cools J. Expert Rev Anticancer Ther. 2009 Sep;9(9):1295-304.
4. Hypereosinophilic syndrome variants: diagnostic and therapeutic considerations.
Roufosse F. Haematologica. 2009 Sep;94(9):1188-93.
5. How I treat hypereosinophilic syndromes. Klion AD. Blood. 2009 Oct 9;114(18):3736-
41
6. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Klion A.
Annu Rev Med. 2009;60:293-306.
7. Molecular diagnostics and treatment of patients with the hypereosinophilic syndrome.
Rothenberg ME. Clin Adv Hematol Oncol. 2009 Jan;7(1):43-4.
8. The hypereosinophilic syndromes: current concepts and treatments. Gleich GJ,
Leiferman KM. Br J Haematol. 2009 May;145(3):271-85.

Disclaimer: All information contained within the American Partnership for Eosinophilic
Disorders’ website is intended for educational purposes only. Visitors are encouraged to
consult other sources and confirm the information contained within this site. Consumers
should never disregard medical advice or delay in seeking it because of something they may
have read on this website.
Hypereosinophilic Syndrome
©American Partnership for Eosinophilic Disorders 2010
Edited by: Srdan Verstovsek MD, PhD
Updated 3-11-2011