Phenotype-Specific Associations Between Graft‑Versus‑Host Disease and Post‑Transplant Outcomes

Portia Smallbone¹, Yosra Aljawai¹, George Chen¹

¹Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.

|August 10, 2026

Summary

In post-transplant cyclophosphamide (PTCy) era HCT, immunosuppressive therapy-requiring chronic graft-versus-host disease (GVHD) is linked to lower relapse rates. Severe acute GVHD, however, increases non-relapse mortality, suggesting nuanced GVHD management is crucial.

Area of Science:

Hematopoietic Cell Transplantation
Immunology
Oncology

Background:

Allogeneic hematopoietic cell transplantation (HCT) success is often limited by disease relapse.
The role of graft-versus-host disease (GVHD) in preventing relapse versus causing toxicity is complex, especially with post-transplant cyclophosphamide (PTCy).

Purpose of the Study:

To investigate the relationship between specific GVHD phenotypes and clinical outcomes (relapse, non-relapse mortality (NRM), overall survival (OS)).
To analyze these associations in patients undergoing PTCy-based haploidentical or mismatched unrelated donor (MMUD) HCT.

Main Methods:

Retrospective cohort study of 7,055 patients from the Center for International Blood and Marrow Transplant Research registry (2013-2021).
Utilized multi-state time-dependent Cox proportional hazards models and multi-state random survival forest (MS-RSF) analysis.
Examined time-updated GVHD phenotypes: isolated grade II acute GVHD (aGVHD), grade III-IV aGVHD, mild chronic GVHD (cGVHD), and immunosuppressive therapy-requiring (IST-requiring) cGVHD.

Main Results:

IST-requiring cGVHD was associated with significantly lower relapse hazard (HR 0.74) and overall mortality (HR 0.62) compared to being GVHD-free.
Grade III-IV aGVHD was strongly associated with higher NRM (HR 3.15).
Mild cGVHD and isolated grade II aGVHD showed intermediate, less consistent associations.

Conclusions:

Specific GVHD phenotypes have distinct impacts on HCT outcomes in the PTCy era.
Immunosuppressive therapy-requiring chronic GVHD may confer a graft-versus-leukemia effect, while severe acute GVHD increases mortality risk.
Strategies should differentiate GVHD phenotypes to optimize the balance between GVL activity and treatment-related toxicity.

Keywords:

GVHD PTCy acute graft-versus-host disease chronic graft-versus-host disease graft-versus-leukemia haploidentical HCT mismatched donor HCT post-transplantation cyclophosphamide relapse

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Area of Science:

Background:

Purpose of the Study:

Main Methods:

Main Results:

Conclusions:

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