ECD-Score: a Study on Erdheim-Chester Disease

Predicting Long-term Prognosis in Erdheim-Chester Disease: A New Comprehensive Approach

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that primarily affects adults but may also occur in pediatric patients. It is characterized by the accumulation of foamy histiocytes with a distinctive immunophenotype in multiple anatomical sites, most commonly the long bones, retroperitoneal and perirenal tissues, the heart, the central nervous system, and the pituitary gland. The disease shows marked clinical heterogeneity, ranging from localized and asymptomatic forms to severe manifestations with multiorgan involvement. From a pathogenetic perspective, ECD is mainly driven by gain-of-function mutations affecting the MAPK and PI3K-AKT pathways, particularly the BRAFV600E mutation, leading to aberrant activation of the MAPK and mTOR signaling pathways. The release of pro-inflammatory cytokines and chemokines plays a key role in systemic inflammation and tissue damage, resulting in significant complications and disability depending on the organs involved.

Despite the significant efforts of international research in recent years, particularly given the extreme rarity of the disease (incidence below 5 cases per 10,000,000 adults per year), substantial knowledge gaps remain, especially with regard to the prediction of long-term outcomes, both in terms of survival and disability. Although some prognostic factors associated with survival have already been identified (such as central nervous system involvement), to date only limited-scale studies have systematically evaluated the prognosis of patients with ECD, focusing in particular on factors influencing organ-specific complications. Moreover, in clinical practice, several aspects that significantly affect patients' quality of life tend to be underestimated, partly due to the time required to perform comprehensive assessments using detailed questionnaires designed to quantify disease-related consequences, such as chronic disability, depression, and cognitive impairment. Nevertheless, there is a growing need for and interest in these parameters, commonly referred to as patient-reported outcomes. In light of these considerations, the development and implementation of a comprehensive prognostic score aimed at predicting survival and long-term disease outcomes could improve the overall assessment of patients and provide more accurate and clinically meaningful prognostic information.

Study Overview

• Status: Recruiting
• Conditions: Erdheim-Chester Disease (ECD)

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Augusto Vaglio, Medical Doctor; Phone Number: 055 5662905; Email: augusto.vaglio@meyer.it

Study Locations

• France
  • Paris, France
    • Not yet recruiting
    • Hôpital Pitié-Salpêtrière
    • Contact: Julien Haroche, Medical Doctor
• Italy
  • Fi
    • Florence, Fi, Italy, 50134
      • Recruiting
      • Meyer Children's Hospital IRCCS, Firenze
      • Contact: Augusto Vaglio; Phone Number: 055 5662905; Email: augusto.vaglio@meyer.it
  • Italy
    • Milan, Italy, Italy
      • Not yet recruiting
      • San Raffaele Hospital
      • Contact: Lorenzo Dagna, Medical Doctor
• United Kingdom
  • Newcastel
    • Newcastle, Newcastel, United Kingdom
      • Not yet recruiting
      • Newcastle upon Tyne Hospitals NHS Foundation Trust
      • Contact: Matthew Collin, Medical Doctor
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Not yet recruiting
      • National Institute of Health
      • Contact: Kevin O'Brien, Medical Doctor
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Matthew J. Koster, Medical Doctor
  • New York
    • New York, New York, United States, 10065
      • Not yet recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Eli L. Diamond, Medical Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with ECD will be recruited and will attend outpatient visits at the study coordination center at the Meyer IRCCS University Hospital (Florence) and other participating centers. The patients to be enrolled will be "prevalent" and "incident" patients during the 5-year study period. Patients undergoing follow-up at their respective centers will be involved in the study, as well as those who receive a new diagnosis of ECD during the study period.

Description

Inclusion Criteria:

• informed consent signed by the patient or, for minors, by a parent or legal guardian
• confirmed diagnosis of ECD according to the latest international guidelines (Goyal G, Blood 2020)
• availability of clinical, molecular, treatment and response to therapy data
• a minimum follow-up period of one year.

Exclusion Criteria:

• lack of diagnostic or follow-up data
• refusal or inability to sign the informed consent form

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

patients with Erdheim-Chester disease (ECD); Patients with ECD will be recruited and will attend outpatient visits at the study coordination center at the Meyer IRCCS University Hospital (Florence) and other participating centers. The patients to be enrolled will be "prevalent" and "incident" patients during the 5-year study period. Patients undergoing follow-up at their respective centers will be involved in the study, as well as those who receive a new diagnosis of ECD during the study period. Clinical data will be collected from all patients included, focusing primarily on organ involvement and response to treatment. They will also be asked to complete questionnaires on quality of life and other specific outcomes. Epidemiological data will also be considered, in particular the geographical origin of patients, and survival rates will also be evaluated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time from the patient's enrollment in the study until death or the last available follow-up	5 years
Association between belonging to a clinical cluster and survival	Clinical cluster of ECD	5 years
Association between organ damage and survival	organ damage related to the disease (e.g., chronic kidney failure)	5 years
Association between the treatment used (relative to the historical period) and survival	treatment received	5 years
Association between response to treatment and survival	complete response rate, partial response, stable disease, progression	5 years
Association between treatment toxicity and survival	incidence and severity of adverse events (classified according to CTCAE v6.0)	5 years
Association between comorbidities and survival	presence of malignant tumors and other chronic diseases	5 years
Association between geographical origin and survival	geographical origin	at enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of comorbidities secondary to the disease or treatment (e.g., secondary malignancies)	To assess the incidence of organ damage related to the disease or comorbidities secondary to the disease or the treatment received	5 years
Association between disease and quality of life	Assessment of the impact on quality of life following disease diagnosis and in response to treatment, using validated questionnaires	5 years

Collaborators and Investigators

• Sponsor: Meyer Children's Hospital IRCCS
• Investigators: Principal Investigator: Augusto Vaglio, Medical Doctor, Meyer Children's Hospital IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 2, 2026
• First Submitted That Met QC Criteria: March 2, 2026
• First Posted (Actual): March 6, 2026

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Hemic and Lymphatic Diseases; Erdheim-Chester Disease
• Other Study ID Numbers: ECD-Score

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No