The results of imatinib therapy for patients with primary eosinophilic disorders

To the Editor: Primary eosinophilia is considered to be clonal or idiopathic. Clonal eosinophilia occurs in a wide spectrum of hematological malignancies and is demonstrated to be a part of a malignant clone or it can also result from cytokine-secreting T-cell clone (1). Idiopathic hypereosinophilic syndrome (HES) is defined by persistent eosinophilia ‡1.5 · 10/L for at least 6 months, absence of reactive causes of eosinophilia, and evidence of organ damage (2). A subset of patients with FIP1L1-PDGFRA (Fip1-like1-platelet-derived growth factor receptor alpha) -positive HES demonstrated rapid clinical improvement and hematologic/molecular remission after imatinib therapy (3). We report here on eight patients (pts)with primary eosinophilia (four pts HES, two pts chronic eosinophilic leukemia PDGFRA+, one pt MPD-HES (myeloproliferative disorder-hypereosinophilic syndrome), one pt T-cell mediated HES) treated with imatinib at a starting dose of 100 mg daily. There were five male and three female patients, with a median age of 54.5 yr (range 19–65). Median white blood cell count at diagnosis was 14 · 10/L (range 9.7–30.0), with peripheral blood eosinophilia of 6.34 · 10/L (3.9–24) and bone marrow eosinophilic infiltration of 32% (14–47%). Median serum immunoglobulin E (IgE) level was 168 IU (9–1617). Serum vitamin B12 level was in the normal range (median 350 pg/mL). In one patient, flow cytometric analysis of lymphoid cells showed a population of CD2+CD3+CD4+CD8) lymphocytes. On multiplex polymerase chain reaction (PCR) with heteroduplex analysis, this patient revealed TCRab gene rearrangement. The samepatient presented also t(6;11)(21q;23q) on cytogenetic evaluation. Normal karyotype was showed in the remaining seven pts. A FIP1L1-PDGFRAfusion genewas detectable in two of seven pts at diagnosis (28%) by reverse transcription (RT)-PCR.All patients had an associated organ involvement. Because of refractoriness to the primary therapy, imatinib at 100 mg a daywas initiated in all patients. Median time from diagnosis to imatinib commencement was 53 months (4–144). Median serum troponin level before therapy was 0.2 ng/mL (0.0–9.2). A complete hematologic remission defined as peripheral eosinophilia count <0.7 · 10/L was achieved in three pts, all male, after median of 14 d (range 13–65). Two out of three were FIP1L1PDGFRA positive at diagnosis, one patient was not studied for this transcript. One out of two FIP1L1PDGFRA-positive patients also achieved molecular remission at 6 months. In one patient, imatinib was stopped after 7 months, while in complete remission. After 5 months off imatinib, eosinophilia recurred. This patient was not studied for FIP1L1-PDGFRA transcript at diagnosis, but hewas negative at time of relapse. In two other patients (FIP+), who had been in sustained remission for 6 months, imatinib was stopped, but eosinophilia re-appeared within 1 month. All three pts resumed imatinib at 100 mg a day with complete hematologic remission within next 2 weeks of therapy. Soon thereafter imatinib dose was reduced to 100 mg once a week. Median follow-up of treatment is +6 months (+6 to +24). Imatinib is well tolerated and no side effects are present. Currently, all patients receive imatinib as a maintenance at dose 100 mg a week with sustained remission. Figure 1 presents reduction of eosinophilia count during imatinib in responder group. Eur J Haematol 2006: 76: 535–536 doi:10.1111/j.1600-0609.2006. 00652.x All rights reserved 2006 The Authors Journal compilation 2006 Blackwell Munksgaard