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Antithymocyte globulin in reduced-intensity conditioning regimen allows a high disease-free survival exempt of long-term chronic graft-versus-host disease.
Biol Blood Marrow Transplant. 2014 Mar; 20(3):370-4.BB

Abstract

Nonmyeloablative (NMA) regimens allow the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients considered unfit for standard myeloablative conditioning (MAC) regimens using high-dose alkylating agents with or without total body irradiation (TBI). Reduced-intensity conditioning (RIC) regimens, based on fludarabine (Flu), busulfan (Bu), and rabbit antithymocyte globulin (r-ATG), represent an intermediate alternative between NMA and MAC regimens. This platform was subsequently optimized by the introduction of i.v. Bu and the use of 5 mg/kg r-ATG, based on the hypothesis that these modifications would improve the safety of RIC allo-HSCT. Here we report a study conducted at our institution on 206 patients, median age 59 years, who underwent allo-HSCT after conditioning with Flu, 2 days of i.v. Bu, and 5 mg/kg r-ATG (FBx-ATG) between 2005 and 2012. The prevalence of grade III-IV acute graft-versus-host disease (GVHD) was 9%, and that of extensive chronic GVHD was 22%. Four-year nonrelapse mortality (NRM), relapse, and overall survival (OS) rates were 22%, 36%, and 54%, respectively. NRM tended to be influenced by comorbidities (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] <3 versus HCT-CI ≥3: 18% versus 27%; P = .075), but not by age (<60 years, 20% versus ≥60 years, 25%; P = .142). Disease risk significantly influenced relapse (2 years: low, 8%, intermediate, 28%, high, 34%; very high, 63%; P = .017). Both disease risk (hazard ratio [95% confidence interval]: intermediate, 2.1 [0.8 to 5.2], P = .127; high, 3.4 [1.3 to 9.1], P = .013; very high, 4.0 [1.1 to 14], P = .029) and HCT-CI (hazard ratio [95% confidence interval]: HCT-CI ≥3, 1.7 (1.1 to 2.8), P = .018) influenced OS, but age and donor type did not. The FBx-ATG RIC regimen reported here is associated with low mortality and high long-term disease-free survival without persistent GVHD in both young and old patients. It represents a valuable platform for developing further post-transplantation strategies aimed at reducing the incidence of relapse, particularly in the setting of high-risk disease.

Authors+Show Affiliations

Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano, Italy.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano, Italy.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Aix-Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France; Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France; Inserm CBT-510, Centre d'Investigations Cliniques en Biothérapie, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France; Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France; Inserm CBT-510, Centre d'Investigations Cliniques en Biothérapie, Institut Paoli Calmettes, Marseille, France.Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France; Inserm CBT-510, Centre d'Investigations Cliniques en Biothérapie, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France. Electronic address: blaised@ipc.unicancer.fr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24315846

Citation

Devillier, Raynier, et al. "Antithymocyte Globulin in Reduced-intensity Conditioning Regimen Allows a High Disease-free Survival Exempt of Long-term Chronic Graft-versus-host Disease." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 20, no. 3, 2014, pp. 370-4.
Devillier R, Fürst S, El-Cheikh J, et al. Antithymocyte globulin in reduced-intensity conditioning regimen allows a high disease-free survival exempt of long-term chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20(3):370-4.
Devillier, R., Fürst, S., El-Cheikh, J., Castagna, L., Harbi, S., Granata, A., Crocchiolo, R., Oudin, C., Mohty, B., Bouabdallah, R., Chabannon, C., Stoppa, A. M., Charbonnier, A., Broussais-Guillaumot, F., Calmels, B., Lemarie, C., Rey, J., Vey, N., & Blaise, D. (2014). Antithymocyte globulin in reduced-intensity conditioning regimen allows a high disease-free survival exempt of long-term chronic graft-versus-host disease. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 20(3), 370-4. https://doi.org/10.1016/j.bbmt.2013.11.030
Devillier R, et al. Antithymocyte Globulin in Reduced-intensity Conditioning Regimen Allows a High Disease-free Survival Exempt of Long-term Chronic Graft-versus-host Disease. Biol Blood Marrow Transplant. 2014;20(3):370-4. PubMed PMID: 24315846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antithymocyte globulin in reduced-intensity conditioning regimen allows a high disease-free survival exempt of long-term chronic graft-versus-host disease. AU - Devillier,Raynier, AU - Fürst,Sabine, AU - El-Cheikh,Jean, AU - Castagna,Luca, AU - Harbi,Samia, AU - Granata,Angela, AU - Crocchiolo,Roberto, AU - Oudin,Claire, AU - Mohty,Bilal, AU - Bouabdallah,Reda, AU - Chabannon,Christian, AU - Stoppa,Anne-Marie, AU - Charbonnier,Aude, AU - Broussais-Guillaumot,Florence, AU - Calmels,Boris, AU - Lemarie,Claude, AU - Rey,Jèrôme, AU - Vey,Norbert, AU - Blaise,Didier, Y1 - 2013/12/04/ PY - 2013/10/27/received PY - 2013/11/29/accepted PY - 2013/12/10/entrez PY - 2013/12/10/pubmed PY - 2014/10/21/medline KW - Allogeneic stem cell transplantation KW - Antithymocyte globulin KW - Reduced-intensity conditioning SP - 370 EP - 4 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol. Blood Marrow Transplant. VL - 20 IS - 3 N2 - Nonmyeloablative (NMA) regimens allow the use of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients considered unfit for standard myeloablative conditioning (MAC) regimens using high-dose alkylating agents with or without total body irradiation (TBI). Reduced-intensity conditioning (RIC) regimens, based on fludarabine (Flu), busulfan (Bu), and rabbit antithymocyte globulin (r-ATG), represent an intermediate alternative between NMA and MAC regimens. This platform was subsequently optimized by the introduction of i.v. Bu and the use of 5 mg/kg r-ATG, based on the hypothesis that these modifications would improve the safety of RIC allo-HSCT. Here we report a study conducted at our institution on 206 patients, median age 59 years, who underwent allo-HSCT after conditioning with Flu, 2 days of i.v. Bu, and 5 mg/kg r-ATG (FBx-ATG) between 2005 and 2012. The prevalence of grade III-IV acute graft-versus-host disease (GVHD) was 9%, and that of extensive chronic GVHD was 22%. Four-year nonrelapse mortality (NRM), relapse, and overall survival (OS) rates were 22%, 36%, and 54%, respectively. NRM tended to be influenced by comorbidities (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] <3 versus HCT-CI ≥3: 18% versus 27%; P = .075), but not by age (<60 years, 20% versus ≥60 years, 25%; P = .142). Disease risk significantly influenced relapse (2 years: low, 8%, intermediate, 28%, high, 34%; very high, 63%; P = .017). Both disease risk (hazard ratio [95% confidence interval]: intermediate, 2.1 [0.8 to 5.2], P = .127; high, 3.4 [1.3 to 9.1], P = .013; very high, 4.0 [1.1 to 14], P = .029) and HCT-CI (hazard ratio [95% confidence interval]: HCT-CI ≥3, 1.7 (1.1 to 2.8), P = .018) influenced OS, but age and donor type did not. The FBx-ATG RIC regimen reported here is associated with low mortality and high long-term disease-free survival without persistent GVHD in both young and old patients. It represents a valuable platform for developing further post-transplantation strategies aimed at reducing the incidence of relapse, particularly in the setting of high-risk disease. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/24315846/Antithymocyte_globulin_in_reduced_intensity_conditioning_regimen_allows_a_high_disease_free_survival_exempt_of_long_term_chronic_graft_versus_host_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(13)00567-3 DB - PRIME DP - Unbound Medicine ER -