A subset of patients presenting with hypereosinophilic syndrome (HES) have clinical features consistent with a myeloproliferative disorder. These patients have aggressive disease characterized by tissue fibrosis, including endomyocardial fibrosis and myelofibrosis and a poor prognosis with 5 year mortality rates as high as 50%, if left untreated. The peripheral blood mononuclear cells of the overwhelming majority of these patients have an interstitial deletion in chromosome 4, leading to the formation of the imatinib-sensitive FIP1L1/PDGFRA fusion gene, thus fulfilling the WHO criteria for a diagnosis of chronic eosinophilic leukemia (CEL). We have established a novel RT-PCR assay to test for FIP1L1/PDGFRA fusion gene in peripheral blood samples of patents with eosinophilia. Positive patients are followed over time and treatment responses to imatinib are monitored using this novel RT-PCR assay. Results show that patients show dramatic clinical response within one week of initiation of the therapy with imatinib and achieve molecular remission within 1-12 months. Imatinib dose de-escalation study is in progress. Patients are monitored every month to determine the lowest dose necessary to maintain molecular remission.
| Klion, Amy D; Robyn, Jamie; Maric, Irina et al. (2007) Relapse following discontinuation of imatinib mesylate therapy for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia: implications for optimal dosing. Blood 110:3552-6 |
| Maric, Irina; Robyn, Jamie; Metcalfe, Dean D et al. (2007) KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. J Allergy Clin Immunol 120:680-7 |
