Peripheral Blood KIT-D816V Mutation in Adult Systemic Mastocytosis (PB-KIT in SM)

Study on the Diagnostic Value of Peripheral Blood KIT-D816V Mutation Detection in Adult Systemic Mastocytosis

This observational study aims to evaluate the diagnostic value and clinical utility of detecting the KIT-D816V mutation in the peripheral blood of adult patients with systemic mastocytosis (SM), using droplet digital PCR (ddPCR). Currently, the diagnosis of SM relies heavily on invasive bone marrow biopsies. This study will determine whether highly sensitive ddPCR testing of peripheral blood could provide a reliable, minimally invasive alternative for detecting the KIT-D816V mutation, which is a key driver of the disease and a major diagnostic criterion. The results could optimize the diagnostic process and continuous monitoring of adult SM patients.

Study Overview

• Status: Recruiting
• Conditions: Systemic Mastocytosis; KIT-D816V Mutation

Detailed Description

Systemic mastocytosis (SM) is a rare hematologic neoplasm characterized by the abnormal clonal proliferation and accumulation of mast cells in various organs, most notably the bone marrow. The somatic KIT-D816V mutation is identified in over 90% of adult patients with SM and serves as a major World Health Organization (WHO) diagnostic criterion.

Traditionally, detecting this mutation and definitively diagnosing SM requires a bone marrow aspiration and biopsy, which are invasive, painful, and carry procedural risks. While peripheral blood allele burdens are generally lower than those in the bone marrow, the advent of ultra-sensitive molecular techniques, such as droplet digital PCR (ddPCR), has opened new avenues for non-invasive testing.

This study (ID: SZ-SM02) is designed to systematically investigate the efficacy of detecting the peripheral blood KIT-D816V mutation in adult SM patients. By utilizing ddPCR, we will quantify the mutant allele burden in peripheral blood samples and correlate these findings with matched bone marrow biopsy results, clinical symptom severity, and disease subtypes. The primary objective is to assess the sensitivity, specificity, and overall diagnostic accuracy of peripheral blood ddPCR compared to the gold-standard bone marrow evaluation. Secondary objectives include evaluating the feasibility of using peripheral blood mutational burden as a dynamic biomarker for monitoring disease progression and treatment response. Ultimately, this study seeks to validate a less invasive diagnostic pathway that reduces the burden on patients while maintaining high diagnostic precision.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Suning Chen, Professor; Phone Number: +86-13814881746; Email: chensuning@sina.com
• Study Contact Backup: Name: Suning Chen Chen, Professor; Phone Number: +86-13814881746; Email: chensuning@sina.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology
      • Contact: Suning Chen, Professor; Phone Number: +8613814881746; Email: chensuning@sina.com

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of two main cohorts: adult patients presenting with symptoms indicative of suspected systemic mastocytosis (SM) who require diagnostic evaluation, and a control cohort of adult patients diagnosed with non-SM hematologic diseases. Participants will be recruited from the clinical setting during their standard care visits.

Description

Inclusion Criteria:

• Age >= 18 years.
• Presenting with recurrent idiopathic anaphylactic reactions (e.g., hypotension, syncope), mast cell activation syndrome (MCAS)-related symptoms (flushing, abdominal pain, diarrhea), urticaria pigmentosa, or histopathological findings of mast cell aggregation.
• No prior treatment with KIT inhibitors or drugs affecting mast cell function (e.g., corticosteroids, interferon, immunosuppressants).
• Willingness to undergo bone marrow examination and peripheral blood KIT-D816V testing, consent to biannual clinical follow-up for 6 months, and signing of the informed consent form.

Exclusion Criteria:

• Patients from whom specimens cannot be obtained (e.g., due to comorbidities or coagulation abnormalities preventing sufficient peripheral blood collection or bone marrow biopsy).
• Prior diagnosis of other clonal hematologic diseases (e.g., other types of leukemia or lymphoid malignancies) that could interfere with the specificity of the KIT-D816V mutation assessment.
• Treatment with targeted KIT drugs (e.g., imatinib, avapritinib) within the last 3 months.
• Systemic corticosteroid, interferon, or immunosuppressive therapy within the last 1 month.
• Refusal to participate or inability to complete follow-up due to severe comorbidities or other personal reasons.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Suspected Systemic Mastocytosis (SM) Patients; Adult patients with suspected systemic mastocytosis (SM). Matched peripheral blood and bone marrow samples will be collected from these patients for the detection and quantification of the KIT-D816V mutation via droplet digital PCR (ddPCR).
Non-SM Hematologic Disease Patients (Control); Adult patients diagnosed with non-SM hematologic diseases, serving as the control cohort. Matched peripheral blood and bone marrow samples will be collected for comparative KIT-D816V mutation analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the diagnostic efficacy of peripheral blood KIT-D816V mutation detection using ddPCR for Systemic Mastocytosis (SM).	To evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Area Under the Curve (AUC) of ddPCR detection of the KIT-D816V mutation in peripheral blood for the diagnosis of SM, compared to bone marrow biopsy.	At the time of diagnosis and initial bone marrow biopsy.

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2025
• Primary Completion (Estimated): May 19, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 26, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mast Cell Activation Disorders; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Mastocytosis; Mastocytosis, Systemic
• Other Study ID Numbers: SZ-SM02

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