TDM-Based ATG Dosing Improves GRFS in Haploidentical TransplantTrial shows tailored dosing improves graft-versus-host disease outcomes

Cancer letters Published October 12, 2026 Study authors: Dou Liping, Wang Nan, Zhang Haoyang, Yang Jingjing, Du Jishan, Liu Qingyang, Zhang Xiawei, Li Fei, B… PubMed ↗ NCT05166967 ↗ DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

TDM-based ATG dosing improved GRFS and reduced chronic GVHD and infections versus fixed dosing in haploidentical transplant.

A phase 3 randomized trial tested therapeutic-drug-monitoring (TDM)-based, dose-optimized anti-thymocyte globulin (ATG) against standard weight-based fixed dosing (10 mg/kg) in 204 patients undergoing unmanipulated haploidentical haematopoietic stem cell transplantation. The primary endpoint, 365-day graft-versus-host disease-free and relapse-free survival (GRFS), was significantly higher with TDM-based dosing: 66.7% versus 50.0% (HR 0.666; 95% CI, 0.4456 to 0.9954; P = 0.048).

Secondary outcomes favored the TDM-based group. The cumulative incidence of moderate to severe chronic GVHD at day 365 was 9.8% with TDM-based dosing versus 22.5% with fixed dosing (P = 0.026). Grade 3-5 infections occurred in 44.1% versus 70.6% (P < 0.001). More patients in the TDM-based group achieved optimal ATG exposure (P = 0.007), and CD4 T-cell reconstitution was superior (P = 0.002).

These findings support the clinical utility of individualized ATG dosing for GVHD prophylaxis in this transplant setting. The trial was multicenter, and the results suggest a causal link between TDM-based dosing and improved outcomes, with high certainty for the reported endpoints.

Limitations include the specific evaluation of unmanipulated haploidentical transplants, which may restrict generalizability to other transplant types. Funding and conflicts of interest were not reported.

How this fits prior evidence

How this fits prior evidence: This finding addresses a gap in the management of graft-versus-host disease by providing evidence for individualized dosing. It complements the finding that low-dose ATG plus PTCy shows no significant difference in acute GVHD compared to standard regimens by suggesting that the precision of the dose, rather than just the amount, impacts outcomes. It also aligns with the role of precision diagnostics and novel biomarkers in improving the management of the graft-versus-host disease clinical spectrum.

Researchers conducted a Phase 3 clinical trial to compare two ways of dosing anti-thymocyte globulin (ATG). This medication is used to prevent graft-versus-host disease, a serious condition that can occur after a stem cell transplant. The study involved 204 patients undergoing unmanipulated haploidentical hematopoietic stem cell transplants. One group received a standard weight-based dose, while the other received a dose optimized through therapeutic-drug monitoring (TDM).

The results showed that patients receiving the tailored, TDM-based dose had a higher rate of survival free from graft-versus-host disease and relapse at one year. Additionally, this group had a lower rate of severe chronic graft-versus-host disease and significantly fewer severe infections compared to the group receiving the standard dose. The tailored approach also led to better T-cell recovery.

While the study suggests that personalized dosing is more effective, it is important to note that these findings specifically involve unmanipulated haploidentical transplants. Patients and doctors should discuss how these specific results apply to individual treatment plans, as every transplant case is unique.

What this means for you:

Tailored ATG dosing may improve survival and reduce severe complications in specific stem cell transplant patients.

Common questions

What is the main benefit of the tailored dosing strategy?

The tailored dosing strategy showed a 66.7% survival rate free from graft-versus-host disease and relapse at one year, compared to 50.0% in the fixed dosing group. It also resulted in significantly fewer severe infections, with only 44.1% of patients in the tailored group experiencing grade 3-5 infections compared to 70.6% in the fixed group.

How does this treatment affect graft-versus-host disease (GVHD)?

The study found that the tailored dosing approach led to a lower incidence of moderate to severe chronic graft-versus-host disease at one year. Specifically, the incidence was 9.8% in the tailored group versus 22.5% in the group receiving the standard weight-based dose.

Who specifically was included in this study?

This study included 204 patients who were undergoing unmanipulated haploidentical hematopoietic stem cell transplant. The results specifically support the use of tailored dosing for this specific type of transplant to help manage graft-versus-host disease.

Study Details

Study typeRct

Sample sizen = 204

EvidenceLevel 2

PublishedOct 2026

PMID42508748

TrialNCT05166967

View Original Abstract ↓

Anti-thymocyte globulin (ATG) has been a standard prophylaxis for graft-versus-host disease (GVHD). However, the pharmacokinetics of ATG in vivo vary significantly, and weight-based fixed dosing may not optimize efficacy while minimizing toxicity. We investigated the clinical results of a therapeutic-drug-monitoring (TDM)-based, dose-optimized ATG strategy versus weight-based fixed dosing in haploidentical haematopoietic stem cell transplantation (NCT05166967). Patients were randomly assigned in a 1:1 ratio to receive a targeted dose of ATG or a fixed dose of 10 mg/kg. The primary endpoint was the 365-day graft-versus-host disease-free and relapse-free survival (GRFS). From January 1, 2022, to January 16, 2024, 204 patients were enrolled, with 102 patients in each group. The 365-day GRFS was higher in the targeted dose group (66.7%) than in the fixed dose group (50.0%; hazard ratio [HR], 0.666; 95% confidence interval [CI], 0.4456 to 0.9954; P = 0.048). The cumulative incidence of moderate to severe chronic GVHD at day 365 was significantly lower in the targeted dose group (9.8%; 95% CI, 5.0 to 16.5) compared with the fixed dose group (22.5%; 95% CI, 15.0 to 31.1; P = 0.026). Fewer grade 3-5 infections were reported in the targeted dose group (44.1%) than in the fixed dose group (70.6%; P < 0.001). More patients in the targeted dose group achieved optimal ATG exposure (P = 0.007) and superior CD4 T-cell reconstitution (P = 0.002). These findings support the clinical utility of a TDM-based individualized ATG dosing strategy that balances efficacy and toxicity for GVHD prophylaxis in allogeneic stem cell transplantation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05166967.

TDM-Based ATG Dosing Improves GRFS in Haploidentical TransplantTrial shows tailored dosing improves graft-versus-host disease outcomes

How this fits prior evidence

Common questions

Study Details

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TDM-Based ATG Dosing Improves GRFS in Haploidentical TransplantTrial shows tailored dosing improves graft-versus-host disease outcomes

How this fits prior evidence

Common questions

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