GVHD and Immune Reconstitution With Different ATLG Doses

By Patrick Daly - Last Updated: October 24, 2022

Anti-T-lymphocyte globulin (ATLG) administered prior to allogeneic hematopoietic cell transplantation (HCT) has shown promise in preventing severe graft-versus-host disease (GVHD). However, according to Radwan Massoud and colleagues in Germany, data on the impact of different ATLG doses is sparse.

In their study, published in Bone Marrow Transplantation, they reported that ATLG dose has a significant impact on immune reconstitution but not GVHD. Notably, the researchers also found that higher doses of ATLG were associated with delayed engraftment and increased incidence of infection.

Compared to antithymocyte globulin (ATG), which is derived from rabbit vaccination with human thymocytes, rabbit ATLG is derived from the human Jurkat T-cell line.

When working with ATG, nurses need to distinguish between rabbit or horse formulations in clinical trials due to the clinical practice implications. Horse ATG has more side effects, including the potential for an anaphylactic reaction, so it requires a test dose. In addition, rabbit ATG has a longer half-life and causes more severe and prolonged neutropenia and immunosuppression than horse ATG.

Higher ATLG Dose Reduces GVHD but Increases Side Effects

The retrospective study included 73 and 216 patients who received ATLG 30 mg/kg and 60 mg/kg, respectively, after undergoing myeloablative matched unrelated donor peripheral blood stem cell allogeneic HCT. Researchers used multicolor flow to assess T, B natural killer (NK), and natural killer T cells at 30, 100, and 180 days after transplantation.

According to the report, the 60 mg/kg group had significantly delayed neutrophil and platelet engraftment, as well as higher cumulative incidences of infections (67% vs 75%; P=.049) and Epstein-Barr virus (EBV) reactivation (21% vs 41%; P=.049) at day 100.

Comparatively, the 30 mg/kg group had faster reconstitution of naïve B cells (P<.0001) and γδ T cells (P=.045) at day 30 and faster reconstitution of naïve helper T cells (P=.046), NK cells (P=.035), and naïve B cells at day 180. Lastly, the authors noted there were no significant differences in acute GVHD (aGVHD), chronic GVHD, nonrelapse mortality, relapse incidence, progression-free survival, and overall survival between the doses.

Ultimately, the authors concluded that “higher [ATLG] doses reduce aGVHD. However, they delay engraftment; impair B-cell, γδ T-cell, NK, and CD4+ T-cell reconstitution; and increase the risk for infection and EBV reactivation.” They did add that long-term outcomes were comparable.

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