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<10-5) and extensive cGVHD (HR, 0.30; P<10-5) 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.
|Keywords||Adult acute lymphoblastic leukemia, Anti-thymocyte globulin (ATG), Graft-versus-host disease, Stem cell transplantation|
|Persistent URL||dx.doi.org/10.1002/cncr.31354, hdl.handle.net/1765/105571|
Czerw, T, Labopin, M, Giebel, S, Socie, G, Volin, L, Fegueux, N, … Nagler, A. (2018). 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. Cancer. doi:10.1002/cncr.31354