Anti-thymocyte globulin improves survival free from relapse and graft-versus-host disease after allogeneic peripheral blood stem cell transplantation in patients with Philadelphia-negative acute lymphoblastic leukemia: An analysis by the Acute Leukemia Working Party of the EBMT.

BACKGROUND

Mobilized peripheral blood stem cells are currently the predominant source of grafts for allogeneic transplantation (allogeneic peripheral blood stem cell transplantation [allo-PBSCT]), although, in comparison with bone marrow, their use is associated with an increased risk of chronic graft-versus-host disease (cGVHD). Attempts to reduce the incidence of cGVHD include the addition of anti-thymocyte globulin (ATG) to the pretransplant conditioning regimen.

METHODS

The goal of this retrospective study was to analyze the effect of ATG on allo-PBSCT outcomes for adults with Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL). The primary endpoint was survival free from relapse, grade 3 to 4 acute graft-versus-host disease (aGVHD), and cGVHD (ie, graft-versus-host disease-free/relapse-free survival [GRFS]). Nine-hundred twenty-four patients who underwent unmanipulated allo-PBSCT in their first complete remission between 2007 and 2016 were included. ATG was used in 97 of the 494 transplants from matched sibling donors (20%) and in 307 of the 430 transplants from human leukocyte antigen-matched (8 of 8 loci) unrelated donors (71%).

RESULTS

The use of ATG was an independent factor for an improved chance of GRFS (hazard ratio [HR], 0.70; P = .0009). Furthermore, it was associated with a reduced risk of both grade 2 to 4 (HR, 0.66; P = .005) and grade 3 to 4 aGVHD (HR, 0.58; P = .03). Similarly, its addition reduced the incidence of both total (HR, 0.45; P < 10 ) and extensive cGVHD (HR, 0.30; P < 10 ) as well as nonrelapse mortality (HR, 0.58; P = .01). No significant effect was found with respect to leukemia-free or overall survival. However, an increased risk of relapse was noted for those who received ATG (HR, 1.40; P = .04).

CONCLUSIONS

Patients with Ph-neg ALL treated with allo-PBSCT benefit from the use of ATG in terms of improved GRFS. Its use may, therefore, be considered in this setting. Cancer 2018;124:2523-33. © 2018 American Cancer Society.