Comprehensive Analysis of Diagnosis, Treatment and Outcome in a Retrospective Cohort of HES Patients in the South-West of the Netherlands between 2000-2020

Background

Hypereosinophilic syndrome (HES) encompasses a rare group of disorders, defined by persistent elevation of eosinophilic granulocytes in the peripheral blood or in tissue, with a lack of other explanations for the eosinophilia, and the presence of associated end-organ damage.

The rarity of HES adds to the difficulty of data centralization and true numbers indicating prevalence and treatment are lacking for the Netherlands.

Aim

We performed a retrospective analysis of HES patients in the South-West of the Netherlands with regards to primary HES diagnosis, presenting symptoms, complications, age, sex, and comorbidities. We further aimed to elucidate the role of cardiac involvement in morbidity and mortality, and to analyze the effects of the treatments given to patients and to report outcome.

Furthermore, we aimed to characterize (L-)HES patients in terms of T-cell populations, and analyze the frequency of normal or aberrant T-cell phenotypes as well as the frequency of clonal T-cell populations.

Methods

Retrospective analysis was performed on all patients who were referred to our institution for a HES FISH from the years 2000 to 2020.

Medical records of patients in the aforementioned HES FISH list were analyzed to retrieve the following information: primary diagnosis, associated conditions, organ involvement, presenting symptoms, age, sex, co-morbidities, cardiac involvement, treatment received, T-cell immunophenotyping, TCR rearrangement analysis, mortality, and outcome.

Results

349 patients were referred for a HES FISH test within our institution. Medical records of 130 of these patients were available for data collection and analysis. 82 (63%) of these patients had received HES as a primary diagnosis while 48 (37%) patients had an alternative diagnosis to explain their eosinophilia. Of these 130 patients, 6 (5%) patients had the 4q12 deletion resulting in the FIP1L1-PDGFRA fusion gene (table 1).

Symptoms at presentation were highly variable and manifested in any organ system. The pulmonary (67, 52%), constitutional (59, 45%), dermatologic (55, 42%) and gastro-intestinal (35, 27%) systems were most frequently affected. This was followed by ENT (30, 23%), cardiac (28, 22%), neurologic (23, 18%) and rheumatic symptoms (21, 16%).

Of the 82 HES patients, 14 (17%) patients had cardiac involvement in varying degrees.

In terms of non-steroidal treatment, 22 (26%) patients were on hydroxycarbamide, 18 (21%) on interferon, 17 (20%) on imatinib, and 19 (22%) on anti-IL5 agents (i.e. mepolizumab, benralizumab). Anti-IL5 treatment was the most effective treatment (74%), followed by imatinib (39%), hydroxycarbamide (23%), and interferon (17%). It should be noted that imatinib was also administered to patients who did not have the FIP1L1-PDGFRA fusion gene. Imatinib was 100% effective in the 6 patients with the fusion gene, and 33% effective in the 12 patients without the fusion gene (p = .308). Interferon had the highest rate of intolerance (30%), followed by hydroxycarbamide (28%).

We found concordance between sensitive T-cell phenotyping and TCR gene analysis with PCR in L-HES patients, while (mostly small) clonal T-cell populations were found by PCR in non L-HES patients.

Conclusion

In this cohort study, we present a comprehensive dataset to characterize a group of patients diagnosed with HES. This study adds to knowledge concerning HES patients with regards to clinical presentation, cardiac morbidity, mortality, advanced diagnostics including cellular and molecular techniques, treatment used, treatment efficacy, and clinical outcome.