Higher Dose of ATLG Effective for GVHD Prevention in Sibling Donor SCT

A higher dose of anti-T-lymphocyte globulin (ATLG) significantly outperformed a lower dose in preventing graft-vs-host disease (GVHD) in patients receiving matched –sibling donor (MSD) peripheral blood stem cell transplantation (PBSCT), according to a retrospective study published in Bone Marrow Transplantation.¹

In the study by University Medical Center Hamburg-Eppendorf, Hamburg, Germany, moderate/severe chronic GVHD at 2 years was significantly higher with the 15-mg/kg dose at 43% vs 28% with the 30 mg/kg dose (P =.045), and multivariate analysis associated the higher dose with longer GVHD relapse-free survival (GRFS).

Addressing Dosing Uncertainty in MSD-PBSCT

ATLG is a rabbit-derived antilymphocyte globulin given to prevent acute and chronic GVHD after allogeneic SCT, as is antithymocyte globulin (ATG) which is more commonly available in the United States.

The single-center retrospective analysis of 165 consecutive patients addressed a critical gap in transplant research. Although ATLG is established for reducing GVHD, no prior studies had specifically compared dosing regimens within the MSD-PBSCT setting. An international consensus recommendation for ATLG is 30 mg/kg in MSD and 60 mg/kg with a matched unrelated donor.² Investigators compared outcomes for 71 patients receiving 15 mg/kg and 94 patients receiving 30 mg/kg to determine if the increased immunosuppression of the higher dose outweighed potential risks of infection or relapse.¹

Superior Control of Chronic GVHD

The primary findings highlight a dramatic improvement in moderate/severe GVHD control with the higher dose. No other factors showed significant effect on chronic GVHD, and multivariate analysis supported the difference in dose (HR, 0.450; 95% CI, 0.214-0.946; P =.035).

Multivariable analysis revealed that ATLG-30 was independently associated with improved GRFS, with an HR of 0.47 (P =.02). This indicates that the higher dose effectively reduces the burden of GVHD without increasing the cumulative incidence of relapse or nonrelapse mortality (NRM).

Cumulative incidence of all-grade chronic GVHD at 2 years was 73% with 15 mg/kg vs 62% with 30 mg/kg, showing no significant difference (P =.21). Acute GVHD cumulative incidence at 100 days was 13% with 15 mg/kg vs 9% with 30 mg/kg, which was also not significant (P =.7). The 15 mg/kg dose was associated with slightly earlier leukocyte (11 vs 12 days) and platelet (12 vs 15 days) engraftment.

In addition to the reduction in moderate to severe chronic GVHD at 2 years, in 108 patients with acute myeloid leukemia or myelodysplastic syndrome who did not receive total body irradiation (TBI), the benefit was even more pronounced, with moderate/severe chronic GVHD rates of 38% for the low dose vs only 19% for the high dose (P =.039). In 39 of these patients who received reduced-intensity conditioning, there were no statistically significant differences between the dose levels.

Propensity score matching was used to balance the groups, yielding 19 matched cases and 31 matched controls. The 2-year cumulative incidence of NRM was 30% with 15 mg/kg and 0% with 30 mg/kg, and no significant differences were observed in other end points.

Survival and Relapse Outcomes

At the 2-year mark, the rate of overall survival (OS) was 72% for the 15 mg/kg group and 77% for the 30 mg/kg group, a difference that did not reach statistical significance (P =.20). The estimated 2-year progression-free survival (PFS) rate was 60% with 15 mg/kg and 65% with 30 mg/kg (P =.4). Lower OS was associated with worse ECOG performance status and lower PFS was associated with negative cytomegalovirus serology. NRM was 13% with 15 mg/kg vs 6% with 30 mg/kg, which was not significant (P =.11). The cumulative incidence of relapse at 2 years was similar between the groups, with rates of 25% and 28%, respectively (P =.64).

Comparative Significance and Clinical Implications

Investigators noted that unlike other studies in mismatched or unrelated donor settings, these data provide specific guidance for clinicians managing the most common donor type: matched siblings. In the setting of MSD-PBSCT, data is lacking on optimal dose of ATLG. Different doses of ATG have also been investigated in several studies

Importantly, the trial demonstrated that the higher dose achieved this superior GVHD protection without sacrificing the graft-vs-tumor effect, as evidenced by the lack of difference in relapse or overall survival between the 2 groups. This study provides evidence that the higher dose can be used effectively in the MSD setting.

REFERENCES

1. Massoud R, Klyuchnikov E, Heidenreich S, et al. Impact of anti-T-lymphocyte globulin dosing on graft versus host disease in matched sibling peripheral blood stem cell transplantation. Bone Marrow Transplant. Published online January 21, 2026. doi:10.1038/s41409-025-02761-5.

2. Bonifazi F, Rubio MT, Bacigalupo A, et al. Rabbit ATG/ATLG in preventing graft-versus-host disease after allogeneic stem cell transplantation: consensus-based recommendations by an international expert panel. Bone Marrow Transplant. 2020;55(6):1093-1102. doi:10.1038/s41409-020-0792-x