Development and Validation of the FIP Score for the Screening of FIP1L1::PDGFRA-Associated Hypereosinophilic Syndrome

Abstract

Background: The FIP1L1-PDFGRA (F/P)-associated hypereosinophilic syndrome (HES) is a rare condition. The F/P fusion gene testing is one of the first-line investigations in patients with unexplained eosinophilia and yields poor diagnostic performance.

Objective: To build and validate the factor interacting with PAPOLA and CPSF1 (FIP) score: a set of weighted criteria warranting testing for the F/P fusion gene.

Methods: We merged data from 151 patients with F/P-associated HES and 320 patients with either F/P-negative HES (n = 279) or hypereosinophilia of undetermined significance (n = 41). Training and validation cohorts (comprising, respectively, 90% and 10% of all patients) were randomly dichotomized. Variables with a P value less than .20 in univariate analysis were included in the multivariable forward-backward logistic regression model to assess their independent contribution to testing positive for the F/P fusion gene. Beta coefficients from multivariable logistic regression were used to assign points for the construction of the score.

Results: Age younger than 66 years, male sex, splenomegaly, lymphomatoid papulosis, absence of gastrointestinal involvement, high serum vitamin B₁₂, high serum tryptase, and normal serum immunoglobulin E levels were the 8 variables retained in the model. The best cutoff value was greater than 48. The model yielded a sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve, respectively, of 88.3%, 93.7%, 87.1%, 94.4%, and 0.962 in the training dataset and of 85.7%, 97.0%, 85.7%, and 97.0%, 0.986 in the validation dataset.

Conclusions: The FIP score highlights the need for closely selecting patients with hypereosinophilia for whom F/P fusion gene testing should be performed, resulting in medical time reduction and substantial cost-savings.

Keywords: Clinical medicine; Cost savings; Diagnosis; Diagnostic test; Eosinophilia; FIP1L1-PDGFRA fusion protein; Hypereosinophilic syndrome; Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions.