Successful treatment of cardiac manifestation of eosinophilic leukemia

Abstract

A 37-year-old male patient presented to the stroke unit of our neurology department with weakness and paresthesia of the right arm and slight anomia. Physical examination revealed distal palsy of both arms, predominantly on the right side. No other pathologic findings were observed. Cranial MRI revealed bilateral territorial infarction in the supply territories of the middle and posterior cerebral arteries. A 12-lead electrocardiography showed incomplete right bundle branch block, negative T waves and ST depression in II, III, aVF and V4–V6 (Fig. 1a). Transesophageal and transthoracic echocardiography revealed normal dimensions of both ventricles with regular systolic and diastolic function. No intracardiac thrombi and no patent foramen ovale could be detected at that time. HolterECG did not show paroxysmal atrial fibrillation. Carotid artery stenosis was ruled out by duplex ultrasound. Blood examination showed increased creatinine (1.59 mg/dL) and urea (60 mg/dL). The white cell count was 13.2 9 10/L, with 6.9 9 10/L eosinophils (52%). A screening for vasculitis was unremarkable aside from an ANA titer of 1:320. Stool analysis and serologic tests were unsuspicious for parasitic helminth infection and there was no apparent primary allergic disorder. Because of the drastically increased eosinophils, we suspected a myeloproliferative disorder. A bone marrow biopsy was done, showing increased myelopoiesis and megakaryopoiesis as well as massive eosinophilia. These findings led us to the diagnosis of hypereosinophilic syndrome (HES). The firstline therapy for HES is steroids [3]; so, we started treatment with prednisone. Antiplatelet therapy with aspirin was administered because of the stroke. As it may have influence on the treatment, it is necessary to further classify the disease by cytogenetic and molecular genetic analysis. During these diagnostic procedures, a chromosomal deletion on 4q12 leading to creation of the FIP1L1–PDGFRA fusion gene was detected. This gene encodes a protein displaying constitutive tyrosine kinase activity. Thus, the final diagnosis was F/P ? chronic eosinophilic leukemia (CEL) [7] and the tyrosine kinase inhibitor imatinib, which is regarded as first line therapy for this special disease subgroup [3, 7], was administered at a dose of 100 mg/day. A control echocardiography was performed 2 months later, revealing an elastic echogenic mass filling the left ventricular apex (Fig. 1b; Movie 1) and right ventricular involvement. These findings could be confirmed in further follow-up studies. Cardiac magnetic resonance (CMR) also confirmed the presence of thrombotic formations in the left and right ventricular apex (Fig. 1d). Strikingly, leukocyte count was normalized to 9.1 9 10/L with 0.5% eosinophils at this point of time. No FIP1L1–PDGFRA transcripts were detectable, so a complete molecular genetic remission was achieved. The patient remained clinically stable without symptoms. Echocardiography follow-up was continued and after 1 year of therapy with imatinib, a clear regression of cardiac involvement could be assessed, since the left and right ventricular echogenic masses could not be detected any longer (Fig. 1c; Movie 2). Chronic eosinophilic leukemia is part of the heterogenous group of HESs. As these are very rare, there are no published Electronic supplementary material The online version of this article (doi:10.1007/s00392-010-0143-9) contains supplementary material, which is available to authorized users.