Plasma ctDNA Monitoring in Pediatric Acute Leukemia

Официальное название

A Retrospective-Prospective Observational Cohort Study of Peripheral Blood Plasma ctDNA Compared With Bone Marrow MFC-MRD, ddPCR, and RNA Sequencing in Pediatric Acute Leukemia

Обзор

This retrospective-prospective observational cohort study aims to evaluate peripheral blood plasma circulating tumor DNA (ctDNA) dynamics in pediatric acute leukemia and compare ctDNA results with concurrent bone marrow multiparameter flow cytometry minimal residual disease (MFC-MRD), droplet digital PCR (ddPCR), and RNA sequencing findings. The study includes a retrospective cohort with available clinical and molecular data and a prospective cohort with serially collected peripheral blood and bone marrow samples at predefined treatment time points. The study will assess consistence between plasma ctDNA and conventional bone marrow-based assays, characterize longitudinal ctDNA dynamics, and explore the association between ctDNA patterns and relapse or survival outcomes.

Подробное описание

Minimal residual disease assessment is essential for treatment response evaluation and risk stratification in pediatric acute leukemia. Conventional MRD monitoring mainly relies on bone marrow-based assays, including multiparameter flow cytometry, molecular assays, and sequencing-based methods. However, repeated bone marrow sampling is invasive, and peripheral blood plasma ctDNA may provide a minimally invasive approach for dynamic disease monitoring.

This study will include pediatric patients with acute leukemia who have available peripheral blood plasma ctDNA testing data and corresponding clinical or molecular information. Existing clinical records, laboratory results, leukemia-related genetic findings, bone marrow MFC-MRD results, ddPCR results, RNA sequencing results, treatment information, and follow-up outcomes will be retrospectively collected. After study registration, follow-up outcomes and additional serial molecular monitoring data will be prospectively collected when available.

Peripheral blood plasma cfDNA/ctDNA results will be compared with matched or corresponding bone marrow-based assessments, including MFC-MRD, ddPCR, and RNA sequencing. The study will evaluate the concordance between plasma ctDNA and conventional bone marrow-based assays at different treatment time points, including diagnosis, pre-transplantation, post-transplantation, follow-up, and suspected relapse when available.

The study will further assess ctDNA clearance, persistence, or re-emergence during treatment and follow-up. Exploratory analyses will evaluate whether ctDNA dynamics are associated with treatment response, relapse, event-free survival, relapse-free survival, and overall survival.

Первичные конечные точки

• Consistence between peripheral blood plasma ctDNA and bone marrow MFC-MRD [Срок оценки: From the date of enrollment to 6 months after hematopoietic stem cell transplantation, assessed up to 6 months post-transplantation.]

Вторичные конечные точки (3)

• Event-free survival [Срок оценки: The time from diagnosis to relapse, death from any cause, or last follow-up, whichever occurs first, assessed up to 36 months.]
• Overall survival [Срок оценки: From the date of diagnosis until the date of death from any cause or last follow-up, whichever occurs first, assessed up to 36 months.]
• ctDNA clearance rate [Срок оценки: From the date of enrollment to 6 months after hematopoietic stem cell transplantation, assessed up to 6 months post-transplantation.]

Критерии участия

Критерии включения

• Patients diagnosed with pediatric acute leukemia, including acute lymphoblastic leukemia, acute myeloid leukemia, or mixed phenotype acute leukemia.
• Age younger than 18 years at diagnosis.
• Availability of peripheral blood plasma cfDNA/ctDNA testing data.
• Availability of clinical data and at least one corresponding bone marrow-based assessment, including MFC-MRD, ddPCR, RNA sequencing.
• For prospectively collected follow-up data or samples, written informed consent will be obtained from parents or legal guardians.
• For retrospectively collected data, consent procedures will follow the approval of the institutional ethics committee.

Критерии исключения

• Patients without available peripheral blood plasma cfDNA/ctDNA data.
• Patients with insufficient clinical or laboratory data for analysis.
• Samples failing cfDNA/ctDNA quality control.
• Withdrawal of consent for prospective follow-up or additional sample collection.
• Patients judged by the investigator to be unsuitable for inclusion.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Department of Pediatric Hematology/Oncology,Institute of Hematology and Blood Disease Hosp — Тяньцзинь

Идентификаторы

NCT: NCT07751588 · IIT2026086

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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