U.S. ResidentsHYPEREOSINOPHILIC SYNDROME (HES)/ CHRONIC EOSINOPHILIC LEUKEMIA (CEL)
Image of an eosinophil from an electron micrograph.1
HES
HES refers to a group of disorders in which there are very high numbers of eosinophils in the blood ≥6 months for which no cause can be determined, eventually leading to inflammation and damage to organs such as the heart, lungs, gastrointestinal tract, brain, or skin.2
Epidemiology
- The exact incidence of HES is unknown. According to one estimate, 1 or 2 new cases can be expected each year per 200,000 individuals3
- The disorder primarily affects males (male to female ratio, 9:1)3
- Peak incidence is in the fourth decade of life4
Presenting symptoms
- Presenting symptoms may be sudden and dramatic, but more often, the onset is insidious and may involve almost any organ system5
- Patient may present with3
- Chronic, persistent cough
- Loss of intellect, depressed mood, and poor coordination
- Peripheral neuropathy
- Adie's syndrome (pupillotonia), kerato-conjunctivitis sicca, and scleritis
- Vasculitis
- Endomyocardial fibrosis
- Patient may present with3
CEL
Like HES, patients with CEL exhibit eosinophilia with evidence of organ involvement.4
Patients with CEL are distinguished from those with HES by the presence of an acquired clonal cytogenetic mutation.4
Epidemiology
- The true incidence of CEL is unknown4
- CEL has been reported to be more common in males, with peak incidence in the fourth decade of life4
Presenting symptoms
- Patients may present with constitutional symptoms such as fatigue, weight loss, night sweats, and fever6
Prescribing GLIVEC
PRESCRIBING GLIVEC FOR HYPEREOSINOPHILIC SYNDROME (HES)/ CHRONIC EOSINOPHILIC LEUKEMIA (CEL)
GLIVEC is indicated for the treatment of adult patients with advanced HES and/or CEL with FIP1L1-PDGFRa rearrangement.1*
Dose increase from 100 mg to 400 mg may be considered in the absence of adverse drug reactions if assessment demonstrates an insufficient response to therapy.1
Treatment should be continued as long as the patient continues to benefit.1
| Dose adjustments for neutropenia and thrombocytopenia in HES/CEL with FIP1L1-PDGFRa1 | ||
|---|---|---|
| HES/CEL (starting dose 100 mg) | ANC <1.0 x 109/L and/or Platelets <50 x 109/L |
|
| HES/CEL (starting dose 400 mg) | ANC <1.0 x 109/L and/or Platelets <50 x 109/L |
|
Special Warnings
In patients with HES and cardiac involvement, isolated cases of cardiogenic shock/left ventricular dysfunction have been associated with the initiation of imatinib therapy. The condition was reported to be reversible with the administration of systemic steroids, circulatory support measures, and temporarily withholding imatinib. As cardiac adverse events have been reported uncommonly with imatinib, a careful assessment of the benefit/risk of imatinib therapy should be considered in the HES/CEL population before treatment initiation. Myelodysplastic/myeloproliferative diseases with PDGFR gene rearrangements could be associated with high eosinophil levels. Evaluation by a cardiology specialist, performance of an echocardiogram, and determination of serum troponin should therefore be considered in patients with HES/CEL and in patients with MDS/MPD associated with high eosinophil levels before imatinib is administered. If either is abnormal, follow-up with a cardiology specialist and the prophylactic use of systemic steroids (1–2 mg/kg) for 1 to 2 weeks concomitantly with imatinib should be considered at the initiation of therapy.1
Response rates seen in patients with HES/CEL receiving GLIVEC 75 mg/day to 1000 mg/day in clinical trials and published case reports†
| Response in HES/CEL2 | |||
|---|---|---|---|
| Cytogenetic abnormality | Number of patients | Complete hematologic response | Partial hematologic response |
| n (%) | n (%) | ||
| Positive FIP1L1-PDGFRa fusion kinase | 61 | 61 (100%) | 0 (0%) |
| Negative FIP1L1-PDGFRa fusion kinase | 56 | 12 (21%) | 9 (16%) |
| Unknown cytogenetic abnormality | 59 | 34 (58%) | 7 (12%) |
| Total | 176 | 107 (61%) | 23 (13%) |
* In HES/CEL patients, the efficacy of GLIVEC is based on hematologic response rates. There are no controlled trials demonstrating a clinical benefit or increased survival for these diseases.1
†Fourteen patients aged 16 to 64 years with HES/CEL treated with 100 mg to 1000 mg of GLIVEC daily were studied in an open-label, multicenter, phase 2 clinical trial that was conducted testing GLIVEC in diverse populations of patients with life-threatening diseases involving Abl, KIT, or PDGFR protein tyrosine kinases. Thirty-five published case reports and case series describe the use of GLIVEC dosed from 75 mg to 800 mg daily in 162 additional patients with HES/CEL aged 11 to 78 years. Response durations for these additional patients ranged from 6+ weeks to 44 months.2
References
References
- Schwartz RS. The hypereosinophilic syndrome and the biology of cancer. N Engl J Med. 2003;348(13):1199-1200.
- HES: information about hypereosinophilic syndrome. American Partnership for Eosinophilic Disorders (APFED) Web site.
- Karnak D, Kayacan O, Beder S, Delibalta M. Hypereosinophilic syndrome with pulmonary and cardiac involvement in a patient with asthma. CMAJ. 2003;168(2):172-175.
- Kamineni P, Baptiste A, Hassan M, et al. Case of chronic eosinophilic leukemia with deletion of chromosome 16 and hepatitis C. J Natl Med Assoc. 2006;98(8):1356-1360.
- Samavedi V, Sacher RA, Herrin VE, Files JC, Zhou Y, Schick P. Hypereosinophilic syndrome. http://www.emedicine.com/med/topic1076.htm. Updated October 4, 2009. Accessed August 17, 2010.
- Leukemia. Cleveland Clinic Web site. http://my.clevelandclinic.org/disorders/leukemia/hic_leukemia.aspx. Accessed August 17, 2010.
