Validated Risk Score May Help Forecast Acute GVHD Following Allo-HCT

A newly developed clinical risk score may help physicians estimate the likelihood of acute graft-vs-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (allo-HCT), according to results of a large registry-based analysis published in Blood Advances.¹

The model, derived and validated in nearly 22,000 adult transplant recipients, stratified patients into risk groups with substantially different probabilities of developing clinically significant aGVHD by day 100 after transplant.

Investigators reported that patients in the highest risk quartile had more than triple the odds of developing grade 2 to 4 aGVHD compared with those in the lowest quartile.¹ If validated prospectively, the tool could help clinicians personalize transplant planning, guide patient counseling, and identify candidates for preventive strategies or clinical trials targeting graft-versus-host disease.

Trial Overview

The study by Caden M. Ulschmid, MD, of the Medical College of Wisconsin, and colleagues for the Center for International Blood and Marrow Transplant Research (CIBMTR), analyzed data from 21,796 adults who underwent first allo-HCT between 2008 and 2019.¹ Eligible patients had a broad range of transplant indications including hematologic malignancies, aplastic anemia, and sickle cell disease and were treated across diverse donor types, conditioning regimens, graft sources, and GVHD prophylaxis approaches.

Participants were randomly assigned into a training cohort (70%; n = 15,258) and a validation cohort (30%; n = 6538). Logistic regression modeling was used to identify baseline clinical variables associated with the development of aGVHD.

The primary end point was development of grade 2 to 4 aGVHD within 100 days after transplant. A secondary end point was grade 3 to 4 aGVHD.

Overall, grade 2 to 4 aGVHD occurred in approximately 39% of patients in both the training and validation cohorts, while grade 3 to 4 disease occurred in 15% in both cohorts.

When patients were stratified by quartiles of the derived risk score, the probability of developing grade 2 to 4 aGVHD ranged from 26% in the lowest risk group to 52% in the highest. Compared with the lowest quartile, the odds ratios for grade 2 to 4 aGVHD were 1.50 for the 25^th to 50th percentile group, 2.07 for the 50^th to 75th percentile group, and 3.15 for the > 75th percentile group.

A similar gradient was observed for severe aGVHD. Patients in the highest quartile had a predicted probability of grade 3 to 4 disease of 24%, compared with 9% in the lowest quartile.

Factors Influencing aGVHD Risk

The model incorporates multiple baseline clinical variables readily available before transplant. These included patient characteristics, disease features, donor characteristics, conditioning regimen, and GVHD prophylaxis strategies.

Among the most influential factors associated with aGVHD risk were conditioning regimen intensity, donor type and graft source, GVHD prophylaxis regimen, use of antithymocyte globulin or alemtuzumab, and underlying disease and disease status.

Nonmyeloablative and many reduced-intensity conditioning regimens were associated with significantly decreased odds of aGVHD compared with traditional myeloablative regimens. In addition, grafts from HLA-identical sibling donors were associated with lower aGVHD risk than peripheral blood stem cell grafts from matched unrelated donors. The analysis also found that GVHD prophylaxis regimens incorporating posttransplant cyclophosphamide were associated with reduced risk compared with tacrolimus plus methotrexate.

Clinical Context

Allogeneic hematopoietic cell transplantation remains a potentially curative therapy for many hematologic malignancies and selected nonmalignant disorders. However, aGVHD continues to be one of the most serious complications after transplant.

Historically, grade 2 to 4 aGVHD develops in approximately 30% to 50% of transplant recipients, with severe forms contributing substantially to nonrelapse mortality and infectious complications.²

Although numerous clinical and biologic factors associated with aGVHD have been identified, including donor compatibility, conditioning intensity, and immune biomarkers, few tools have translated this knowledge into a widely applicable clinical prediction model. Earlier attempts to predict aGVHD risk have often focused on specific diseases or transplant settings, limiting generalizability.

The new risk score was designed to address this gap by incorporating a wide range of transplant indications and clinical scenarios commonly encountered in practice.

Interpretation and Potential Applications

The investigators emphasized that the model is intended to complement clinical judgment based on factors available to a physician at a patient’s bedside. In the validation cohort, the concordance statistic was approximately 0.62 for both grade 2 to 4 and grade 3 to 4 aGVHD.

The score may provide a standardized framework for assessing baseline risk prior to transplantation, with potential applications including informing donor selection or conditioning strategies, identifying patients for intensified prophylaxis approaches, stratifying patients in clinical trials evaluating GVHD prevention, and counseling patients regarding transplant-related risks.

Investigators acknowledged that the dataset predates the wider use of posttransplant cyclophosphamide which would exceed the 16% included in the study as well as the approval of abatacept (Orencia), both of which have been used to reduce the severity of aGVHD.

An online calculator based on the modelhas been made publicly available through the CIBMTR to estimate individual patient risk using the included clinical variables.

REFERENCES

1. Ulschmid CM, Li X, Wang T, et al. Validated clinical risk score for acute graft-versus-host disease in adult allogeneic hematopoietic cell transplantation. Blood Advances. 2026;10(4):1348-1356. doi:10.1182/bloodadvances.2025016938

2. K Kim HT, Soiffer RJ, Cutler C, et al. Reduced incidence of relapse and graft-versus-host disease in acute myeloid leukemia after allogeneic hematopoietic cell transplantation. Haematologica. 2025;110(9):1998-2008. doi:10.3324/haematol.2025.287390