Tomasz Czerw1, Myriam Labopin2,3, Sebastian Giebel1, Gérard Socié4, Liisa Volin5, Nathalie Fegueux6, Tamás Masszi7, Didier Blaise8, Sridhar Chaganti9, Jan J Cornelissen10, Jakob Passweg11, Johan Maertens12, Maija Itälä-Remes13, Depei Wu14, Mohamad Mohty2,3, Arnon Nagler3,15. 1. Department of Bone Marrow Transplantation and Oncohematology, Maria Sklodowska-Curie Institute - Oncology Center, Gliwice, Poland. 2. Department of Hematology and Cell Therapy, Saint-Antoine Hospital, Paris, France. 3. The Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation Office, Saint-Antoine Hospital, Paris, France. 4. Department of Hematology, St. Louis Hospital, Paris, France. 5. Department of Medicine, Helsinki University Hospital, Helsinki, Finland. 6. Department of Clinical Hematology, Lapeyronie University Hospital Center, Montpellier, France. 7. Third Department of Internal Medicine, St Istvan and St Laszlo Hospital, Semmelweis University, Budapest, Hungary. 8. Department of Hematology and Transplant Program, Institute Paoli Calmettes, Marseille, France. 9. Department of Haematology, Queen Elizabeth Hospital, Birmingham, United Kingdom. 10. Department of Hematology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, The Netherlands. 11. Department of Hematology, University Hospital, Basel, Switzerland. 12. Department of Haematology, University Hospital Gasthuisberg, Leuven, Belgium. 13. Division of Medicine, Department of Hematology and Stem Cell Transplantation Unit, Turku University Hospital, Turku, Finland. 14. Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China. 15. Division of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Abstract
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. Cancer 2018;124:2523-33.
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. Cancer 2018;124:2523-33.