Systematic Evaluation of Hypereosinophilic Syndrome-Related Organ Damage According to FIP1L1-PDGFRA Status and Response to the Therapy: Analysis from Prospective Clinical Trial with Imatinib Mesylate.
Authors: Rondoni Michela , Paolini Stefania , Vigna Ernesto , Merante Serena , Malagola Michele , Piccaluga Pier Paolo , Buccisano Francesco , Tiribelli Mario , Zaccaria Alfonso , Baccarani Michele , Martinelli Giovanni 
Published: April 2020

Idiopathic hypereosinophilic syndrome (HES) is a rare hematological disorder characterized by persistent eosinophilia presenting often with organ involvement. The increased blood and tissue levels of eosinophils (eos) appear to produce tissue damage via local release of toxic substances producing inflammation and fibrosis. Data from the literature are fragmentary and deduced from several historical series. The most commonly involved organs reported are cardiovascular, pulmonary, cutaneous and neurologic systems. Cardiac disease is described as the major cause of morbidity and mortality. Due to the new knowledge about myeloproliferative variant of HES and PDGFRA rearrangement, we tried to identify different clinical picture. The aim of this retrospective analysis is to evaluate the prevalence of HES-related organ damage, its relation to F/P status, and response to imatinib therapy. A prospective multicenter study of the HES began in 2001. Patient enrolled had HES diagnosis, independently of presence of FIP1L1-PDGFRA (F/P) rearrangement. 72 patients were treated with IM 100 to 400 mg daily with a median observation time of 28 months (r 12–68). 33 patients (46%) were positive for the F/P rearrangement (F/P+), while 39 (54%) were negative (F/P−). At the time of enrolment HES patients were systematically screened for organ damage with instrumental evaluation (chest radiography, echocardiogram, abdomen ultrasonography). Symptoms were considered too, so if respiratory symptoms were presented or a reduction of ejection fraction was found organ involvement was established. Results. Organ involvement was recorded in 42% of F/P+ and in 51% of F/P−. Skin involvement was only recorded in F/P−, whereas splenomegaly was reported in 7 F/P+ and only in one case of F/P−. To date, soft tissue was peculiar site of F/P+ patients. All the 33 F/P+ patients achieved a complete hematologic remission (CHR) and molecular negativity, and together they became negative for organ localization and free of symptoms. In the two patients with soft tissue involvement (temporal/parietal and retro-orbital masses) imaging response was documented with positron emission tomography (PET) and with CT scan one month after the beginning of the therapy. Favourable response was recorded also in patients with cardiac involvement, apiece to grade of fibrosis. 5 out of 39 F/P− patients achieved a transitory CHR, but no durable effects on organ involvement. All these patients are alive. Conclusion. Organ involvement do not seems to be a constant characteristic of HES, irrespective to F/P status, but there are differences between F/P+ and F/P− patients. Organ damage in F/P+ subset is reversible before fibrosis development. In the whole population observed, no deaths were recorded in more than five years.

F/P+(33 pt) F/P−(39 pt) Statistic Organ damage 42% 51% p=NS More than 1 organ involvement 18% 3% p=0,01 Heart 15% 5% p=NS Lung 18% 26% p=NS Spleen 21% 3% 0,001 Skin 0 15% p=0,001 Liver 3% 3% p=NS Soft tissue 6% 0 p=0,1 Skeleton 3% 0 p=NS Gut 0 3% p=NS