Histiocytic Disorder Follow-up Study

The purpose of the study is to describe the burden of chronic health conditions, psychological dysfunction, chronic pain, healthcare utilization, worse health-related quality of life, overall mortality, and cause-specific mortality among individuals with histiocytic disorders

Study Overview

• Status: Recruiting
• Conditions: Histiocytosis; Langerhans Cell Histiocytosis; Erdheim-Chester Disease; Rosai Dorfman Disease; Xanthogranuloma; Malignant Histiocytoses

Detailed Description

Background

Over the last decade, major advances have occurred in histiocytic disorders with the discovery of MAPK-ERK pathway mutations leading to targeted therapeutics using BRAF- and MEK-inhibitors. However, there is a lack of large studies informing the burden of morbidity and mortality among people with histiocytosis. Institutional studies in pediatric LCH suggest that survivors suffer from long-term impairment of health related quality of life, cognitive dysfunction, pituitary dysfunction, and hearing difficulties in 20-50% cases. Studies from the investigative team and others have also shown a high incidence of acute myeloid leukemia and other second primary malignancies in pediatric and adult LCH. Chronic medical conditions may arise as a function of the disease biology or due to cancer therapy, as seen in other hematologic malignancies.

Design

Retrospective cohort study aimed at determining the risk of chronic health conditions and cause-specific mortality in pediatric and adult patients with histiocytic disorders. The study will include patients from the Histiocytosis Association registry and other institutions including UAB (n~6000). The participants will complete a validated questionnaire capturing details of chronic health conditions, health related quality of life, cognitive/psychological function, and healthcare utilization.

Future directions

The results from our study will be instrumental in formulating follow-up guidelines for histiocytic disorders and developing targeted survivorship programs to improve overall outcomes.

• Study Type: Observational
• Enrollment (Estimated): 6000

Contacts and Locations

• Study Contact: Name: Gaurav Goyal, MD; Phone Number: 1-866-438-1640; Email: histio@uabmc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Gaurav Goyal, MD; Phone Number: 1-866-438-1640; Email: histio@uabmc.edu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Individuals with diagnosis of histiocytic disorder are eligible to participate, including family members (next of kin) of deceased individuals.

Description

Inclusion Criteria:

• diagnosis of histiocytic disorder at any age

  1. Langerhans cell histiocytosis,
  2. Erdheim-Chester disease,
  3. Rosai-Dorfman disease,
  4. Xanthogranuloma,
  5. Mixed histiocytosis
  6. Malignant histiocytosis (Histiocytic sarcoma, langerhans cell sarcoma, interdigitating cell sarcoma)
  7. Hemophagocytic lymphohistiocytosis

Exclusion Criteria:

• None

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic health conditions diagnosed after LCH diagnosis graded using the Common Terminology Criteria for Adverse Events (CTCAE), v5.0 (https://ctep.cancer.gov)	The CTCAE criteria for CHCs distinguishes each acute and chronic condition (including SPMs) in persons with cancer from grades 1 through 4 with unique clinical descriptions of severity (grade 1, mild; grade 2, moderate; grade 3, severe; grade 4, life-threatening/disabling). The main outcome will be the number of distinct CTCAE grade 3-4 conditions among LCH cases compared with unaffected (non-cancer) controls.	From diagnosis of histiocytic disorder to age at completion of survey, assessed up to 200 months
All-cause and cause-specific mortality	Causes of death will be grouped into primary cancer (LCH)-related mortality (PCRM) and non-primary cancer-related mortality (NPCRM - death from all causes other than the index LCH diagnosis) by two independent investigators.	2 years preceding death

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Factors associated with new-onset morbidity	We will build a prediction model that has a good discrimination for predicting CHC, SPMs, and psychological outcomes separately using data from the LCH (case) cohort.	From diagnosis to age at completion of survey, assessed up to 200 months

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Gaurav Goyal, MD, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: May 25, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: June 7, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: survivorship; targeted therapy; long-term; second cancer
• Additional Relevant MeSH Terms: Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Lymphatic Diseases; Lung Diseases, Interstitial; Histiocytic Disorders, Malignant; Histiocytosis, Non-Langerhans-Cell; Histiocytosis, Langerhans-Cell; Histiocytosis; Histiocytic Sarcoma; Erdheim-Chester Disease; Histiocytosis, Sinus
• Other Study ID Numbers: IRB-300008744

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No