We have initiated a project in collaboration with Dr. Amy Klion of the National Institute of Allergy and Infectious Diseases to study patients with hypereosinophilic syndrome. It has been recently described that a subgroup of patients with idiopathic hypereosinophilic syndrome (HES) carries the FIP1L1/PDGFRA fusion gene, resulting in dysregulated tyrosine kinase activity. These patients show marked peripheral blood eosinophilia, myeloproliferative bone marrows with increased atypical spindle-shaped mast cells, elevation of serum tryptase levels and serum B12 levels, and dramatic responses to treatment with imatinib mesylate. During the last year we have established a novel RT-PCR assay to detect FIP1L1/PDGFRA fusion gene in patients with peripheral blood 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 currently 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 |
