BOF: Malignant (Myeloproliferative Disease)
- Jul 2, 2016
- 2 min read
A 24 year old man is being treated for FIP1L1/PDGFRalpha POSITIVE myeloproliferative hypereosinophilic syndrome with evidence of cardiac failure. There was no excess circulating or bone marrow aspirate blasts at diagnosis.
He is commenced on treatment with high dose glucocorticoids and imatinib, and the steroids weaned after the second week. He attends the outpatient clinic four weeks later complaining of worsening shortness of breath and ankle swelling and echocardiogram confirms worsening cardiac function.
He has no siblings and a matched unrelated donor search is underway.
His full blood count is as follows:
Hb: 10.2g/dl, WCC: 42.3x10⁹/L, Plt: 138x10⁹/L
Leucocyte differential: 80% eosinophils; 10% neutrophils, 8% lymphocytes, 2% monocytes. No circulating blasts present.
Which of the following therapies is the BEST subsequent line of treatment for his condition?
a) High dose glucocorticoids (1-2mg/kg daily) alone
b) Dasatinib with high dose glucocorticoids
c) Interferon-alfa with high dose glucocorticoids
d) Mepolizumab with high dose glucocorticoids
e) Vincristine with high dose glucocorticoids
Answer:
b) Dasatinib with high dose glucocorticoids
Explanation:
Treatment of FIP1L1/PDGFRalpha positive HES should be with the tyrosine kinase inhibitor (TKI) imatinib as first line, with elevated serum tryptase predicting responsiveness (but also associated with poorer outcome). This should be in combination with corticosteroids in patients with cardiac involvement. Patients developing resistance or intolerance to imatinib should receive second generation TKIs such as dasatinib or nilotinib.
Mepolizumab is humanised anti-interleukin 5 antibody currently available only on clinical protocols for patients with life-threatening HES refractory to standard therapies or with eosionophilic granulomatosis with polyangiitis (Churg Strauss syndrome).
It may find its way into a multi-agent treatment approach in the future. Allogeneic haematopoietic stem cell transplant offers the only chance of long term remission, and reduced intensity conditioning has been tried successfully.
Reference:
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