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

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT07500441

Enrollment

100

Registered

2026-03-30

Start date

2026-03-20

Completion date

2029-12-31

Last updated

2026-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Measurable Residual Disease (MRD), Digital PCR (DPCR), Allogeneic Hematopoietic Stem Cell Transplantation, Clonal Hematopoiesis

Brief summary

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.

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.

Interventions

DIAGNOSTIC_TESTIndividualized 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.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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.

Design outcomes

Primary

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

Secondary

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

Countries

China

Contacts

CONTACTMeng Lv, M.D,Ph.D

drlvmeng@bjmu.edu.cn+861088324637

CONTACTYa-zhen Qin, Ph.D

qin2000@aliyun.com+861088324702

PRINCIPAL_INVESTIGATORYa-zhen Qin, Ph.D

Peking University People's Hospital

PRINCIPAL_INVESTIGATORMeng Lv, M.D,Ph.D