New evidence on graft-versus-host disease prevention in stem cell transplants from unrelated donors

by Isabell Arndt, DKMS - Medizin & Wissenschaft

edited by Lisa Lock, reviewed by Robert Egan

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Anti-T-lymphocyte globulin (ATLG) for the prevention of graft-versus-host disease (GvHD) reduces complications and infection-related mortality compared with post-transplant cyclophosphamide (PTCy) in allogeneic hematopoietic stem cell transplantation from unrelated donors. Although PTCy was associated with fewer cases of acute (Grade II–IV) and chronic GvHD, this did not result in a survival benefit for patients with blood cancer. These initial results from the GRAPPA study were presented by DKMS as a late-breaking abstract at the European Hematology Association Congress (EHA 2026) in Stockholm.

"We observed very low treatment-related mortality in patients receiving ATLG for GvHD prophylaxis, 7% within the first two years. Such a good result has never before been reported from a large study involving unrelated stem cell donors. This is a new milestone," says Prof. Dr. Johannes Schetelig, head of the stem cell transplantation unit at the University Hospital Carl Gustav Carus Dresden and director of clinical research at DKMS.

"The Phase III GRAPPA study is one of the most significant studies led by DKMS's research unit, the Clinical Trials Unit," says Schetelig. The international nonprofit organization drives progress in stem cell transplantation for blood cancer patients worldwide through its own research.

Despite established preventive measures, graft-versus-host disease (GvHD) remains one of the greatest obstacles to long-term success in allogeneic hematopoietic stem cell transplantation (allo-HSCT) from unrelated donors. While post-transplant cyclophosphamide (PTCy) overcomes HLA barriers and reduces the GvHD rate in haploidentical transplants, there is insufficient evidence of its benefit in unrelated donors.

The standard practice in Europe relies primarily on anti-T-lymphocyte globulin (ATLG), although its approval is not valid worldwide. "Despite many years of experience and numerous publications on the potential of both therapies, a direct comparison was lacking," emphasizes Schetelig, who led the GRAPPA study at the DKMS Clinical Trials Unit.

GRAPPA expands the evidence on GvHD prevention

The study was designed to demonstrate that PTCy is not inferior to ATLG in terms of overall survival. "Instead, the study results surprisingly suggest that ATLG is superior," explains Schetelig.

Severe cases of acute (Grade III and IV) and chronic GvHD were comparable in both study arms. Overall, though, PTCy showed fewer cases of acute GvHD Grades II to IV and fewer cases of chronic GvHD and appears to reduce the risk of mild or moderate GvHD in particular. However, this benefit was not reflected in overall survival. Initial analyses from the study showed an efficacy advantage with ATLG compared with PTCy:

• Overall survival two years after randomization: 75% in the ATLG arm vs. 68% in the PTCy arm (hazard ratio (HR)=1.34, p=0.051). Statistically, there was a near-significant advantage in terms of superiority.
• Non-relapse-related or treatment-associated mortality (NRM) two years after allogeneic HSCT: 7% in the ATLG arm vs. 13% in the PTCy arm (HR=1.86, p=0.02).

The increased NRM can be attributed primarily to more frequent infections among PTCy patients. "Simply being aware of this risk can help us take more precautions and respond more quickly," said Schetelig.

High donor availability and standardized study design

The multicenter, randomized Phase III trial enrolled 640 patients who required allogeneic HSCT. Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative neoplasms (MPN) were included. For these patients, unrelated donors with no more than one mismatch at a single HLA locus were available. The study group was randomized in a 3:2 ratio to receive PTCy or ATLG. In addition, all patients received immunosuppressive therapy with tacrolimus and mycophenolate mofetil.

"Thanks to the standardized study design, the high donor availability, and the established networks of German transplant centers, we were able to conduct the studies very quickly," explains Schetelig.

New insights into immunosuppression in GvHD prophylaxis

"GvHD prophylaxis with ATLG in combination with tacrolimus and mycophenolate mofetil remains the standard of care for stem cell transplants from HLA-matched unrelated donors in countries where ATLG is available, as this regimen is highly beneficial for patients," summarizes Schetelig. "However, the potential of PTCy to prevent chronic forms of GvHD in particular should be further explored."

For the use of PTCy, an optimized dosing strategy for immunosuppression and additional monitoring of patients will be crucial to reduce the risk of infection and associated mortality. "These findings can be followed up with many subsequent studies, the results of which may provide even stronger guidance and concrete recommendations for action regarding the use of this prophylactic strategy in the future," says Schetelig.

More information

M. Stelljes et al, GVHD prophylaxis including ATG remains standard of care for HLA-compatible unrelated donor hematopoietic cell transplantation: Results from a large randomized controlled trial comparing ATG and PTCy. Presented at EHA 2026, Stockholm

Key medical concepts

Graft vs Host DiseaseAllogeneic Hematopoietic Stem Cell TransplantationAcute Myeloid Leukemia

Clinical categories

Oncology Provided by DKMS - Medizin & Wissenschaft Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Robert Egan

Bachelor's in mathematical biology, Master's in creative writing. Well-traveled with unique perspectives on science and language. Full profile →

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