Erdheim-Chester Disease (ECD)
Conditions
Brief 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.
Interventions
None listed
Sponsors
Meyer Children's Hospital IRCCS
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of comorbidities secondary to the disease or treatment (e.g., secondary malignancies) | 5 years | To assess the incidence of organ damage related to the disease or comorbidities secondary to the disease or the treatment received |
| Association between disease and quality of life | 5 years | Assessment of the impact on quality of life following disease diagnosis and in response to treatment, using validated questionnaires |
Countries
France, Italy, United Kingdom, United States
Contacts
CONTACTAugusto Vaglio, Medical Doctor
PRINCIPAL_INVESTIGATORAugusto Vaglio, Medical Doctor
Meyer Children's Hospital IRCCS
Outcome results
None listed