ECD-Score: a Study on Erdheim-Chester Disease

Condition(s) studied

Study summary

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.

Eligibility

Primary outcome measure(s)

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

Trial sites (7)

More Meyer Children's Hospital IRCCS trials in France