title: Graft-versus-host disease following allogeneic transplantation from HLA-identical sibling with antithymocyte globulin-based reduced-intensity preparative regimen.
abstract: Reduced-intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT). RIC has been shown to allow engraftment with minimal early transplantation-related mortality (TRM). However, in the context of RIC, predictive factors for acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) and their effect on outcome remain unknown. In this report, we analyzed the outcome of 101 high-risk patients (70 hematologic and 31 nonhematologic malignancies) who received an HLA-identical sibling allo-SCT after RIC, including fludarabine, busulfan, and antithymocyte globulin (ATG). The cumulative incidence of grade II-IV aGVHD was 36% (95% confidence interval [CI], 27%-45%), whereas the cumulative incidence of cGVHD at 2 years was 43% (95% CI, 33%-53%). In multivariate analysis, the incidence of aGVHD was significantly associated with the ATG dose infused during conditioning (P =.0005), whereas peripheral blood as stem cell source was the only predictive factor for the development of cGVHD (P =.0007). The 1-year cumulative incidences of disease progression or relapse in patients with (n = 69) and without (n = 31) GVHD (whatever its form or grade) were 30% (95% CI, 19%-41%) and 55% (95% CI, 37%-72%), respectively (P =.02), suggesting that a potent graft-versus-tumor (GVT) effect can be achieved in high-risk patients following RIC. Moreover, the GVT effect was closely associated with GVHD without an increased risk of TRM (cumulative incidence of TRM, 18% [95% CI, 10%-25%]). Collectively, these results provide a framework for the refinement of RIC approaches designed to enhance the GVT effect with an acceptable risk of GVHD.
authors.affiliation: Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Bay
authors.forename: Catherine
authors.initials: C
authors.lastname: Faucher
authors.forename: Bachra
authors.initials: B
authors.lastname: Choufi
authors.forename: Karin
authors.initials: K
authors.lastname: Bilger
authors.forename: Olivier
authors.initials: O
authors.lastname: Tournilhac
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Stoppa
authors.forename: Diane
authors.initials: D
authors.lastname: Coso
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
authors.forename: Dominique
authors.initials: D
authors.lastname: Maraninchi
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum; D002066:Busulfan; D002908:Chronic Disease; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015994:Incidence; D015993:Life Tables; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000401:mortality / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000706:statistics & numerical data; D012008:Recurrence; D012307:Risk Factors; D035781:Siblings; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives*
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine