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Hemato-Oncology-43-Eosinophilia Diagnosis

HEMATO-ONCOLOGY PART-43

Question: Dr. Chiragbhai, thank you for explaining in last part about approach to eosinophilia, especially concept of AEC, degree, and main differential diagnoses. Now can you tell us more about diagnosis?
Ans: As discussed last time, there is a wide range of conditions that may cause eosinophilia. Most of them are suspected based on good clinical review and basic tests, including blood tests, chest xray and abdominal sonography. If there is no obvious underlying cause, we need to decide need for more tests and urgency for treatment.
In such cases, asymptomatic patients with mild to moderate eosinophilia may be observed for few months as some of them have spontaneous resolution. However, those with severe eosinophilia i.e. AEC over 5000, should be evaluated with bone marrow examination and special tests. These patients generally need treatment right away, due to risk of serious organ injury, as eosinophils contain many toxic cytokines. Most common tests include IgE level, bone marrow aspiration and trephine biopsy with cytogenetics, PDGFR alpha, PDGFR beta, and sometimes FGFR mutation analysis. Also, CML should be ruled out by either bone marrow cytogenetics or by PCR for BCR-ABL, especially with very high WBC.
Thus patients fall in mainly 3 categories:
1. Primary HES (myeloproliferative type – neoplastic)
2. Secondary (reactive) – due to many casues
3. Idiopathic HES – no cause after thorough work up.
Que: What is the role of these special tests?
Ans: Bone marrow examination is essential to rule out myeloproliferative type of eosinophilic disorder, and to rule out eosinophilic leukemia. It is also important to rule out underlying lymphoproliferative disorder before giving any steroid treatment. PDGFR alpha or beta are targets for imatinib therapy. Their presence indicates very good chance that imatinib will work. If positive, imatinib gives excellent results in these patients, even at very low doses. We have a patient with absolute eosinophil count of over 50,000, with excellent response to imatinib. Within 3 weeks, total wbc count and AEC is normal. Compared to 400 mg dose in CML, 200 mg or sometimes even 100 mg is sufficient in these patients. It has to be continued lifelong as in CML.
Que: What about patients who do not have obvious underlying cause?
Ans: Idiopathic HES (hypereosinophilic syndrome) patients range from asymptomatic or mild to severe symptoms with even limb/or organ threatening complications. Those who are asymptomatic can be monitored, but others are treated with a course of steroids. If steroids are ineffective or there is a relapse after steroid taper, hydroxyurea is used. Some start with hydroxyurea to avoid steroid side effects. For resistant patients, treatment is mostly similar to that of a myeloproliferative disorder, such as high dose hydroxyurea or melphalan or interferon alpha. Some patients are resistant to all common agents, and disease is rapidly fatal. Those patients presenting with AEC over 50,000 or so have poor prognosis. There are reports of allogeneic stem cell transplantation for patients who are unresponsive to medicines.
Important aspect of therapy is also monitoring for thrombosis, organ injury especially cardiac. Overall survival has significantly improved with early diagnosis before organ injury, and improved treatment options. 80% survival at 5 years and 40% at 15 years is seen overall.
Mepolizumab is the most recent drug, still not widely available, but on compassionate basis for resistant HES. It is undergoing clinical trials for HES. It is a monoclonal antibody against IL-5 approved for treatment of Churg-Strauss syndrome, which also has eosinophilia as one of the manifestations.

Dr. Chirag A. Shah; M.D. Oncology/Hematology (USA), 079 26754001. Diplomate American Board of Oncology and Hematology. Ahmedabad. drchiragashah@gmail.com Shyam Hem-Onc Clinic. 402 Galaxy, Near Shivranjani, Opp Jhansi ki Rani BRTS, Ahmedabad. www.shyamhemoncclinic.com

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