An interstitial deletion in the long arm of chromosome 4 leads to the formation of a novel fusion gene (FIP1L1-PDGFRalpha) coding for a constitutively activated form of PDGFRalpha. The fusion gene has been identified only in patients with the hypereosinophilic syndrome and has become a marker of clonal HES. The PDGFRalpha transcript can be neutralized by several protein tyrosine kinase inhibitors (PTKI). Recently, imatinib mesylate (IM) has been shown to induce remissions (

Cools J,
N Engl J Med
.
2003
;
348
:
1199
–200
,
Pardanani A,
Blood
2003
;
102
:
3093
–6
,
Cortes J,
Blood
2003
;
102
:
4714
–6)
but remission duration is still undefined. The aim of this study was to evaluate the duration of IM in FIP1L1-PDGFRalpha positive HES patients. Hypereosinophilic syndrome was defined according to Chusid criteria (
Blood
,
1994
;
83
:
2759
–2779
). The FIP1L1-PDGFRalpha transcript was identified and monitored every six months on bone marrow cells using a nested retrospective reverse transcriptase polymerase chain reaction (RT-PCR), as reported by Cools J (
N Engl J Med.
2003
;
348
:
1199
–200
). Twenty-one FIP1L1-PDGFRalpha positive HES patients have been enrolled in a prospective national study of treatment with IM at a daily dose of 400 mg. All patients were male. Median age was 48 years ( range 25–72). All 21 patients achieved a complete hematologic response (CHR) in less than one month. Currently, the median follow-up of all 21 patients is 28 months ( range 13– 67), with 13 patients with a follow-up longer than 2 years. The longest follow-up are 42, 46 and 67 months. All these patients remained in complete hematologic remission and all became PCR negative and have remained PCR negative as of today. All patients are continuing on imatinib, but in several cases the dose has been reduced to 300, 200 or 100 mg daily. No patients developed heart failure.

We conclude that in FIP1L1-PDGFRalpha positive HES patients the therapeutic effect of IM at doses ranging from 400 to 100 mg daily is sustained over time, up to five years, without detectable adverse effects.

Topics:
disseminated eosinophilic collagen disease, follow-up, imatinib mesylate, platelet-derived growth factor alpha receptor, primary eosinophilic endomyocardial cardiomyopathy, disease remission, polymerase chain reaction, reverse transcriptase polymerase chain reaction, adverse effects, heart failure

Disclosure: No relevant conflicts of interest to declare.

Acknowledgments: COFIN 2003 (Molecular therapy of Ph+ leukemias), by FIRB 2001, by the University of Bologna (60%), by the Italian Association for Cancer Research (A.I.R.C.), by the Italian National Research Council (C.N.R), by Fondazione Del Monte of Bologna and Ravenna (Italy) and A.I.L. grants, European LeukemiaNet grants.

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2006, The American Society of Hematology
2006
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