KIT-D816V Mutation, Systemic Mastocytosis
Conditions
Brief summary
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.
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.
Interventions
None listed
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the diagnostic efficacy of peripheral blood KIT-D816V mutation detection using ddPCR for Systemic Mastocytosis (SM). | At the time of diagnosis and initial bone marrow biopsy. | 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. |
Countries
China
Contacts
CONTACTSuning Chen, Professor
CONTACTSuning Chen Chen, Professor
Outcome results
None listed