Digital PCR of CHIP and MR for MRD Monitoring After Allo-HSCT in AML

Digital PCR-Based Detection of CHIP and MR Mutations for Minimal Residual Disease Monitoring After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Acute Myeloid Leukemia

This prospective observational study aims to evaluate the clinical significance of measurable residual disease (MRD) monitoring using digital PCR (dPCR) in patients with acute myeloid leukemia (AML) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study will specifically enroll patients harboring clonal hematopoiesis (CH) and/or myelodysplasia-related (MR) gene mutations.

Patient-specific dPCR assays will be established to enable highly sensitive, longitudinal quantification of mutation burden. Serial assessments will be performed at predefined time points within the first 12 months after transplantation. The study will investigate the prognostic value of dPCR-based MRD dynamics for predicting relapse, relapse-free survival, and overall survival, and will further explore its potential to enable earlier detection of molecular relapse compared with conventional methods.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia (AML)
• Intervention / Treatment: Diagnostic test: Individualized Digital PCR (dPCR) monitoring

Detailed Description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potentially curative treatment for patients with intermediate- and high-risk acute myeloid leukemia (AML). Post-transplant monitoring of measurable residual disease (MRD) is critical for early detection of relapse and timely clinical intervention.

This study focuses on AML patients harboring clonal hematopoiesis (CH) and/or myelodysplasia-related (MR) gene mutations (e.g., DNMT3A, TET2, ASXL1, SRSF2), who lack recurrent fusion genes and NPM1 mutations, representing a population with an unmet need for sensitive molecular MRD monitoring strategies.

For each enrolled patient, an individualized digital PCR (dPCR) assay will be developed to detect patient-specific mutations with high sensitivity. Bone marrow samples will be collected longitudinally at predefined time points (baseline [month 0], and months 1, 2, 3, 4.5, 6, 9, and 12 post-allo-HSCT).

Longitudinal dynamics of mutation burden will be analyzed to evaluate their association with clinical outcomes, including cumulative incidence of relapse (CIR) and overall survival (OS). This study aims to establish dPCR-based MRD monitoring as a precise and clinically actionable tool to guide early intervention and ultimately improve post-transplant outcomes in AML.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Ya-zhen Qin, Ph.D; Phone Number: +861088324702; Email: qin2000@aliyun.com
• Study Contact Backup: Name: Meng Lv, M.D,Ph.D; Phone Number: +861088324637; Email: drlvmeng@bjmu.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

AML patients who underwent allo-HSCT, specifically those lacking common fusion genes and NPM1 mutations but carrying CH and/or MR gene mutations.

Description

Inclusion Criteria:

1. Diagnosis of acute myeloid leukemia (AML).
2. Undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the investigating center.
3. Negative for recurrent fusion genes routinely monitored in the clinical laboratory, including but not limited to AML1::ETO, CBFB::MYH11, KMT2A (MLL) rearrangements, NUP98::NSD1, NUP98::HOXA9, FUS::ERG, DEK::NUP214, SET::NUP214, PICALM::AF10, and BCR::ABL1.
4. Availability of next-generation sequencing (NGS) results at initial diagnosis with accessible original reports.
5. Negative for NPM1 mutations at initial diagnosis.
6. Presence of clonal hematopoiesis (CH) and/or myelodysplasia-related (MR) gene mutations at initial diagnosis, including but not limited to DNMT3A, TET2, ASXL1, SRSF2, SF3B1, U2AF1, JAK2, IDH2, BCOR, EZH2, RUNX1, STAG2, and ZRSR2.

Exclusion Criteria:

1. Patients with mutation profiles unsuitable for the design of patient-specific digital PCR (dPCR) assays achieving a sensitivity of ≤0.1%.
2. Absence of evaluable molecular targets for longitudinal MRD monitoring.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AML post-HSCT Cohort; Patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) who harbor clonal hematopoiesis (CH) and/or myelodysplasia-related (MR) gene mutations, and are negative for recurrent fusion genes and NPM1 mutations.	Diagnostic test: Individualized Digital PCR (dPCR) monitoring; Bone marrow samples are collected at 0, 1, 2, 3, 4.5, 6, 9, and 12 months post-HSCT. DNA is extracted and specific CH/MR mutation burden is quantified using individualized dPCR primer/probe systems.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Incidence of Relapse (CIR)	CIR is defined as the time from transplantation to hematologic or extramedullary relapse	Up to 2 years post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	The time from HSCT to the Death from any cause	Up to 2 years post-transplantation
Relapse-free survival (RFS)	The time from the date of HSCT to the occurrence of any of the following: Death from any cause Disease recurrence	Up to 2 years post-transplantation

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Ya-zhen Qin, Ph.D, Peking University People's Hospital; Principal Investigator: Meng Lv, M.D,Ph.D, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: March 24, 2026
• First Submitted That Met QC Criteria: March 24, 2026
• First Posted (Actual): March 30, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Allogeneic Hematopoietic Stem Cell Transplantation; Clonal Hematopoiesis; Measurable Residual Disease (MRD); Digital PCR (DPCR)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Neoplastic Processes; Leukemia, Myeloid; Leukemia; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Neoplasm, Residual
• Other Study ID Numbers: 2026PHB191-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No