Individualized Application of Anti-Thymocyte Globulin(ATG)in Unrelated Donor Hematopoietic Stem Cell Transplantation

Application of Anti-Thymocyte Globulin(ATG) Individualized Dosing Model in Unrelated Donor Hematopoietic Stem Cell Transplantation

This study aims to compare individualized anti-thymocyte globulin (ATG) dosing versus conventional fixed-dose regimens in unrelated donor peripheral blood stem cell transplantation (URD-PBSCT).

This study notes that URD-HSCT is a key treatment for malignant hematologic diseases and severe bone marrow failure, with rapid expansion in China. However, this study identifies post-transplant CMV infection as a major challenge, adversely affecting survival and quality of life. This study finds that CMV infection compromises immunity and causes multi-organ complications. Given the high costs, long treatment cycles, and limited efficacy of current interventions, this study considers optimizing CMV prevention to be of greater value than expanding treatment options. This study asserts that effective prevention can reduce infection rates and improve overall survival (OS) and long-term prognosis.

This study recognizes that ATG is widely used in URD-HSCT to prevent graft-versus-host disease (GVHD), but its dosage is significantly linked to CMV risk. This study indicates that inadequate ATG exposure increases GVHD risk, while excessive exposure raises viral reactivation (e.g., CMV, EBV) and may cause relapse. This study thus identifies balancing GVHD prevention and infection control as a key clinical goal. This study cites Remberger et al. (2004), who compared ATG doses (4-10 mg/kg) in 162 URD-HSCT patients, finding lower doses increased acute GVHD (aGVHD) and 10 mg/kg raised infection-related mortality, suggesting 6-8 mg/kg as a balanced range. This study also references Bacigalupo et al. (2001), who found no survival differences across doses but noted higher doses reduced severe aGVHD at the cost of increased infection. Therefore, this study concludes that optimal ATG dosing requires balancing GVHD, infection, and relapse.

This study acknowledges that ATG pharmacokinetics (PK) are complex, influenced by dose, body weight, and absolute lymphocyte count (ALC). This study points out that even with fixed dosing, internal exposure (active ATG-AUC) varies greatly among individuals, indicating that fixed dosing is suboptimal and individualized strategies are needed. This study notes that Admiraal et al. developed an ALC-based individualized ATG model, improving immune reconstitution, reducing viral infections, and enhancing OS. However, this study observes that this model was designed for non-myeloablative conditioning and is not applicable to myeloablative conditioning (MAC), which is standard in China.

To address this, this study states that our team initiated ATG PK studies in 2019. This study explains that under MAC, ALC is nearly eliminated, making traditional models unsuitable. By monitoring active ATG-AUC in 106 haploidentical HSCT (haplo-HSCT) patients and using machine learning, this study identified an optimal exposure window of 100-148.5 UE·day/mL. This study found that patients within this window had lower CMV/EBV reactivation without increased GVHD. This study developed a protocol adjusting doses on days -3 and -2 based on ATG concentrations measured on days -5 and -4. This study confirmed through a prospective single-arm study in haplo-HSCT that this regimen reduces CMV/EBV infection and improves disease-free survival (DFS) and OS while maintaining GVHD control.

Given the consistency between URD-PBSCT and haplo-PBSCT in conditioning, GVHD prophylaxis, and CMV prevention-and that CMV infection rates in Chinese URD-PBSCT patients reach 65%-70%-this study extends the individualized ATG protocol to URD-PBSCT to validate its universality across donor sources.

In summary, building on prior haploidentical transplant research, this study applies individualized ATG dosing to URD-PBSCT. This study aims to precisely regulate ATG exposure to reduce CMV infection while maintaining GVHD prophylaxis. This study seeks to improve patient survival and outcomes, laying the foundation for a population PK model and advancing HSCT toward precision medicine.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Drug: Anti-Thymocyte Globulin; Drug: Anti-Thymocyte Globulin

• Study Type: Interventional
• Enrollment (Estimated): 324
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dai-Hong Liu, Dr.; Phone Number: 86-010-66937232; Email: daihongrm@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Li-ping Dou, Dr.; Phone Number: 86-010-66937232; Email: daihongrm@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with indications for allogeneic hematopoietic stem cell transplantation, with malignant hematologic diseases in CR1 or CR2 before transplantation.
2. Have an HLA-matched sibling, unrelated, or haploidentical donor.
3. Age ≥ 14 years and ≤ 65 years.
4. Liver function: ALT and AST ≤ 2.5 × upper limit of normal, bilirubin ≤ 2 × upper limit of normal.
5. Renal function: creatinine ≤ upper limit of normal.
6. No uncontrolled infection or severe mental or psychological disorders.
7. ECOG performance status score of 0-2.
8. Signed informed consent.

Exclusion Criteria:

- 1.No HLA-matched donor. 2.Malignant hematologic disease in CR3 or higher disease stage, or refractory/relapsed status.

3.Patient age < 14 years or > 65 years. 4.Pregnancy of either the donor or the recipient. 5.Presence of mental illness or other conditions that preclude compliance with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control group	Drug: Anti-Thymocyte Globulin; Patients receiving individualized dosing of ATG + standard GVHD prophylaxis regimen; Drug: Anti-Thymocyte Globulin; Patients receiving fixed-dose ATG + standard GVHD prophylaxis regimen
Experimental: Experimental group	Drug: Anti-Thymocyte Globulin; Patients receiving individualized dosing of ATG + standard GVHD prophylaxis regimen; Drug: Anti-Thymocyte Globulin; Patients receiving fixed-dose ATG + standard GVHD prophylaxis regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year GVHD-free and relapse-free survival rate(1-year-GRFS)	The 1-year GVHD-free and relapse-free survival rate (1-year GRFS) is the proportion of patients who, within one year post-treatment, have not experienced: grade III-IV acute graft-versus-host disease (GVHD), moderate-to-severe chronic GVHD requiring systemic immunosuppression, or disease relapse or progression.	1 years after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)	Overall survival (OS) refers to the time from the start of treatment to the death of the patient for any reason.	1 years after treatment
+180 days CMV virus reactivation rate	+180 days CMV virus reactivation rate refers to the time from randomization to CMV virus reactivation, relapse or death within 180 days post-transplant. The actual incidence rate is calculated as the number of patients with events / total number of cases × 100%.	180 days post-transplant
Acute GVHD incidence	Acute GVHD incidence refers to the time from randomization to acute GVHD onset, relapse or death within 100 days post-transplant. The actual incidence rate is calculated as the number of patients with events / total number of cases × 100%.	100 days post-transplant
disease free survival (DFS)	Disease free survival (DFS) refers to the time from treatment to the first lymphoma recurrence.	1 years after treatment
Cumulative incidence of relapse (CIR)	Cumulative incidence of relapse (CIR) refers to the number of patients with hematologic or MRD relapse from randomization to the last follow-up.	1 years after treatment
Cumulative non-relapse mortality (NRM)	Cumulative non-relapse mortality (NRM) refers to death due to non-relapse causes while in complete remission (CR), measured as the number of patients with NRM from randomization to the last follow-up.	1 years after treatment
Treatment-related safety indicators	Treatment-related safety indicators mainly include the cumulative incidence of bacterial infection, viral infection, fungal infection, PTLD, and chronic GVHD from randomization to the last follow-up.	1 years after treatment
Immune reconstitution status	Immune reconstitution status refers to the actual incidence rate calculated as the number of patients with immune reconstitution / total number of cases × 100% from randomization to the last follow-up.	1 years after treatment

Collaborators and Investigators

• Sponsor: Daihong Liu
• Collaborators: Peking University People's Hospital; The First Affiliated Hospital of Zhengzhou University
• Investigators: Study Chair: Dai-Hong Liu, Dr., Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2025
• Primary Completion (Estimated): December 30, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: May 9, 2026
• First Submitted That Met QC Criteria: June 11, 2026
• First Posted (Actual): June 15, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Immune Sera; Antilymphocyte Serum
• Other Study ID Numbers: S2025-1112-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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