Prospective Validation of Engraftment Syndrome Phenotypes and Outcomes After Hematopoietic Stem Cell Transplantation (ES after HSCT)

A Prospective Observational Cohort Study to Validate Engraftment Syndrome Phenotypes and Their Associations With Acute Graft-Versus-Host Disease and Clinical Outcomes After Hematopoietic Stem Cell Transplantation

Engraftment syndrome (ES) is an early inflammatory complication after hematopoietic stem cell transplantation (HSCT) and has been associated with subsequent transplant-related complications and adverse clinical outcomes. However, ES is clinically heterogeneous, and its relationship with acute graft-versus-host disease (aGVHD), survival, and other post-transplant outcomes remains incompletely defined.

This prospective observational cohort study aims to validate previously identified ES-associated risk factors, severity-oriented ES phenotypes, and their associations with grade II-IV aGVHD and clinical outcomes after HSCT. Patients undergoing HSCT will be prospectively followed for the development of ES, grade II-IV aGVHD, and clinical outcomes including overall survival, disease-free survival, relapse, and non-relapse mortality. The study will evaluate whether ES phenotypes and ES-related clinical characteristics can stratify patients according to subsequent aGVHD risk and post-transplant prognosis.

Study Overview

• Status: Not yet recruiting
• Conditions: Engraftment Syndrome; Allo-HSCT
• Intervention / Treatment: Other: No Intervention: Observational Cohort

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Yejun Wu; Phone Number: +8618800181620; Email: wyejun1999@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

The study population will include patients who develop engraftment syndrome after allogeneic hematopoietic stem cell transplantation at the participating center. Patients will be prospectively enrolled after the diagnosis of engraftment syndrome and followed for subsequent grade II-IV acute graft-versus-host disease and post-transplant outcomes, including overall survival, disease-free survival, relapse, and non-relapse mortality. Clinical features, laboratory parameters, engraftment kinetics, and organ-injury markers related to engraftment syndrome will be collected to validate ES phenotypes and their prognostic significance.

Description

Inclusion Criteria:

1. Patients undergoing allogeneic hematopoietic stem cell transplantation at the participating center.
2. Development of engraftment syndrome after hematopoietic stem cell transplantation, diagnosed according to predefined institutional or published clinical criteria.
3. Availability of key clinical and laboratory data required for engraftment syndrome phenotyping, including engraftment kinetics, clinical manifestations, inflammatory markers, and organ-injury parameters.
4. Ability to undergo prospective follow-up for post-transplant outcomes, including acute graft-versus-host disease and survival outcomes.
5. Written informed consent provided by the patient or legally authorized representative, when required by the institutional review board or ethics committee.

Exclusion Criteria:

1. Patients who do not develop engraftment syndrome after hematopoietic stem cell transplantation.
2. Patients with insufficient clinical or laboratory data to confirm the diagnosis of engraftment syndrome.
3. Patients with missing essential follow-up information for assessment of primary outcome measures.
4. Patients who withdraw consent or decline participation in prospective follow-up.
5. Patients enrolled in another study that, in the opinion of the investigators, may interfere with the observational assessment of engraftment syndrome phenotypes or post-transplant outcomes.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients With Engraftment Syndrome; Patients who develop engraftment syndrome after hematopoietic stem cell transplantation will be enrolled and prospectively followed. Engraftment syndrome will be diagnosed according to predefined clinical criteria during the early post-transplant period. Clinical features, laboratory parameters, transplant-related characteristics, ES phenotypes, subsequent grade II-IV acute graft-versus-host disease, and clinical outcomes will be recorded and analyzed.

Other: No Intervention: Observational Cohort; No study-specific intervention will be administered. Participants will receive standard clinical care after hematopoietic stem cell transplantation according to institutional practice and treating physician discretion. The study will prospectively collect observational data on engraftment syndrome characteristics, laboratory parameters, subsequent grade II-IV acute graft-versus-host disease, and clinical outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Grade II-IV Acute Graft-Versus-Host Disease	Time from hematopoietic stem cell transplantation to the first diagnosis of grade II-IV acute graft-versus-host disease among patients with engraftment syndrome. Acute graft-versus-host disease will be graded according to institutional standard criteria.	From hematopoietic stem cell transplantation to the first diagnosis of grade II-IV acute graft-versus-host disease, assessed up to 180 days after transplantation.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade II-IV Acute Graft-Versus-Host Disease	Proportion of participants who develop grade II-IV acute graft-versus-host disease after hematopoietic stem cell transplantation.	Up to 180 days after transplantation.
Incidence of Chronic Graft-Versus-Host Disease	Proportion of participants who develop chronic graft-versus-host disease after hematopoietic stem cell transplantation.	Up to 2 years after transplantation.
Overall Survival	Time from hematopoietic stem cell transplantation to death from any cause. Participants alive at the last follow-up will be censored.	From transplantation to death from any cause, assessed up to 2 years after transplantation.
Disease-Free Survival	Time from hematopoietic stem cell transplantation to relapse, disease progression, or death from any cause, whichever occurs first.	From transplantation to relapse, disease progression, or death from any cause, assessed up to 2 years after transplantation.
Cumulative Incidence of Relapse	Proportion of participants who experience relapse or disease progression after hematopoietic stem cell transplantation. Non-relapse death will be considered a competing event in competing-risk analyses.	Up to 2 years after transplantation.
Non-Relapse Mortality	Death without prior relapse or disease progression after hematopoietic stem cell transplantation. Relapse will be considered a competing event in competing-risk analyses.	Up to 2 years after transplantation.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity-Oriented Engraftment Syndrome Phenotype	Classification of participants into severity-oriented engraftment syndrome phenotypes based on prospectively collected engraftment kinetics, pulmonary involvement, inflammatory burden, and organ-injury markers.	From transplantation to 100 days after transplantation.
Association Between Engraftment Syndrome Phenotype and Grade II-IV Acute Graft-Versus-Host Disease	Association between severity-oriented engraftment syndrome phenotype and subsequent development of grade II-IV acute graft-versus-host disease.	Engraftment syndrome phenotype assessed up to 100 days after transplantation; grade II-IV acute graft-versus-host disease assessed up to 180 days after transplantation.
Association Between Engraftment Syndrome Phenotype and Overall Survival	Association between severity-oriented engraftment syndrome phenotype and overall survival after hematopoietic stem cell transplantation.	Engraftment syndrome phenotype assessed up to 100 days after transplantation; overall survival assessed up to 2 years after transplantation.
Association Between Engraftment Syndrome Phenotype and Disease-Free Survival	Association between severity-oriented engraftment syndrome phenotype and disease-free survival after hematopoietic stem cell transplantation.	Engraftment syndrome phenotype assessed up to 100 days after transplantation; disease-free survival assessed up to 2 years after transplantation.
Performance of an Engraftment Syndrome Risk Stratification Model	Discrimination and calibration of a risk stratification model based on engraftment syndrome-related clinical features and laboratory parameters for predicting post-transplant outcomes.	Predictors assessed up to 100 days after transplantation; outcomes assessed up to 2 years after transplantation.

Collaborators and Investigators

• Sponsor: Xiao Hui Zhang
• Collaborators: Guangzhou First People's Hospital; The First Affiliated Hospital of Zhengzhou University; The Third Xiangya Hospital of Central South University; The First Hospital of Jilin University; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; Guangdong Provincial Hospital of Chinese Medicine, Zhuhai

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: May 3, 2026
• First Submitted That Met QC Criteria: May 3, 2026
• First Posted (Actual): May 11, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 3, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: allo-HSCT; acute GVHD; Engraftment Syndrome
• Other Study ID Numbers: ES-HSCT-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