title: The impact of histopathologic examination of graft-versus-host disease in the era of reduced-intensity conditioning regimen: a study from the Gruppo Italiano Trapianto di Midollo Osseo.
abstract: Reduced-intensity conditioning regimens have reshaped the clinical presentation of graft-versus-host disease after hematopoietic stem cell transplants. However, histopathologic features of graft-versus-host disease following reduced-intensity conditioning regimens have not been fully characterized. In a series of 112 biopsies (skin, n = 60; gastrointestinal [GI] tract, n = 44; liver, n = 8), we described the morphologic profile of graft-versus-host disease following reduced-intensity conditioning and investigated whether histopathologic changes of graft-versus-host disease following reduced-intensity conditioning have a diagnostic and/or prognostic value. Forty-four patients (49.5%) experienced acute graft-versus-host disease, 2 (2.2%) late-onset acute graft-versus-host disease (grade I, n = 13; grade II-IV, n = 33), 24 (27.0%) chronic graft-versus-host disease (de novo n = 12, progressive n = 12) and 19 (21.3%) overlap syndrome. In the skin, we observed: (i) phase-nonspecific changes, such as acute graft-versus-host disease features in chronic graft-versus-host disease patients (n = 4/24; 16.6%), (ii) subtle alterations such as superficial fibrosis in widened dermal papillae (n = 8), in acute graft-versus-host disease/late-onset graft-versus-host disease (n = 6/46; 13.0%) or chronic graft-versus-host disease (n = 2/24, 8.3%) patients, and (iii) features of chronic and acute graft-versus-host disease coexisting in the same specimen in overlap syndrome (n = 3/19; 15.7%). In the GI tract, we did not demonstrate peculiar features differing from those commonly observed in the myeloablative setting. By univariate analysis, a reduced overall survival was associated with graft-versus-host disease type (chronic graft-versus-host disease P = .006, acute graft-versus-host disease P = .03), older age (P = .04), and histopathologic diagnosis of "consistent with" + definite graft-versus-host disease (P = .02). Histopathologic diagnosis retained an independent prognostic value by multivariate analysis (P = .01). The present study indicates that pathologists should be aware of the peculiar morphologic changes of cutaneous graft-versus-host disease following reduced-intensity conditioning and further recommends histopathology in the diagnostic workup of graft-versus-host disease in patients undergoing reduced-intensity conditioning regimen.
authors.affiliation: Division of Anatomic Pathology, Department of Critical Care Medicine and Surgery, University of Florence, Italy. daniela.massi@unifi.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.forename: Cristina
authors.initials: C
authors.lastname: Fondi
authors.forename: Chiara
authors.initials: C
authors.lastname: Nozzoli
authors.forename: Silvia
authors.initials: S
authors.lastname: Benemei
authors.forename: Francesco
authors.initials: F
authors.lastname: Lapi
authors.forename: Luca
authors.initials: L
authors.lastname: Albarello
authors.forename: Claudio
authors.initials: C
authors.lastname: Avellini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bonoldi
authors.forename: Marco
authors.initials: M
authors.lastname: Casini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Cesinaro
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.forename: Vito
authors.initials: V
authors.lastname: Colombetti
authors.forename: Camilla Eva
authors.initials: CE
authors.lastname: Comin
authors.forename: Amedea
authors.initials: A
authors.lastname: Donelli
authors.forename: Mirella
authors.initials: M
authors.lastname: Fortunato
authors.forename: Stefano
authors.initials: S
authors.lastname: Fratoni
authors.forename: Stefano
authors.initials: S
authors.lastname: Guidi
authors.forename: Luca
authors.initials: L
authors.lastname: Messerini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Milone
authors.forename: Davide
authors.initials: D
authors.lastname: Rapezzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Negri
authors.forename: Francesca
authors.initials: F
authors.lastname: Patriarca
authors.forename: Fedro Alessandro
authors.initials: FA
authors.lastname: Peccatori
authors.forename: Maurilio
authors.initials: M
authors.lastname: Ponzoni
authors.forename: Paola
authors.initials: P
authors.lastname: Rafaniello
authors.forename: Roberto
authors.initials: R
authors.lastname: Raimondi
authors.forename: Edvige
authors.initials: E
authors.lastname: Salomone
authors.forename: Andrea
authors.initials: A
authors.lastname: Tendas
authors.forename: Loredana
authors.initials: L
authors.lastname: Villari
authors.forename: Marco
authors.initials: M
authors.lastname: Santucci
authors.forename: Alberto
authors.initials: A
authors.lastname: Bosi
mesh_terms: D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D019172:Transplantation Conditioning; D055815:Young Adult