title: Antithymocyte globulin in reduced-intensity conditioning regimen allows a high disease-free survival exempt of long-term chronic graft-versus-host disease.
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: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
authors: Raynier
authors: R
authors: Devillier
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Sabine
authors: S
authors: Fürst
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Jean
authors: J
authors: El-Cheikh
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
authors: Luca
authors: L
authors: Castagna
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France.
authors: Samia
authors: S
authors: Harbi
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Angela
authors: A
authors: Granata
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Hematology Unit, Humanitas Cancer Center, Istituto Clinico Humanitas, Rozzano, Milano, Italy.
authors: Roberto
authors: R
authors: Crocchiolo
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France.
authors: Claire
authors: C
authors: Oudin
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Bilal
authors: B
authors: Mohty
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Reda
authors: R
authors: Bouabdallah
authors: 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.
authors: Christian
authors: C
authors: Chabannon
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Anne-Marie
authors: AM
authors: Stoppa
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Aude
authors: A
authors: Charbonnier
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Florence
authors: F
authors: Broussais-Guillaumot
authors: 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.
authors: Boris
authors: B
authors: Calmels
authors: Cell Therapy Facility, Institut Paoli Calmettes, Marseille, France; Inserm CBT-510, Centre d'Investigations Cliniques en Biothérapie, Institut Paoli Calmettes, Marseille, France.
authors: Claude
authors: C
authors: Lemarie
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France.
authors: Jèrôme
authors: J
authors: Rey
authors: Hematology Department, Transplantation Program, Institut Paoli Calmettes, Marseille, France; Aix-Marseille Université, Marseille, France; Centre de Recherche en Cancérologie de Marseille (CRCM), Marseille, France.
authors: Norbert
authors: N
authors: Vey
authors: 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.
authors: Didier
authors: D
authors: Blaise
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002066:Busulfan / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: Allogeneic stem cell transplantation; Antithymocyte globulin; Reduced-intensity conditioning