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

Daniela Massi, Cristina Fondi, Chiara Nozzoli, Silvia Benemei, Francesco Lapi, Luca Albarello, Claudio Avellini, Emanuela Bonoldi, Marco Casini, Anna Maria Cesinaro, Fabio Ciceri, Vito Colombetti, Camilla Eva Comin, Amedea Donelli, Mirella Fortunato, Stefano Fratoni, Stefano Guidi, Luca Messerini, Giuseppe Milone, Davide RapezziGiovanni Negri, Francesca Patriarca, Fedro Alessandro Peccatori, Maurilio Ponzoni, Paola Rafaniello, Roberto Raimondi, Edvige Salomone, Andrea Tendas, Loredana Villari, Marco Santucci, Alberto Bosi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)254-268
Number of pages15
JournalHuman Pathology
Volume42
Issue number2
DOIs
Publication statusPublished - Feb 2011

Keywords

  • Bone marrow transplantation
  • Graft-versus-host disease
  • Histopathology
  • Reduced intensity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Massi, D., Fondi, C., Nozzoli, C., Benemei, S., Lapi, F., Albarello, L., Avellini, C., Bonoldi, E., Casini, M., Cesinaro, A. M., Ciceri, F., Colombetti, V., Comin, C. E., Donelli, A., Fortunato, M., Fratoni, S., Guidi, S., Messerini, L., Milone, G., ... Bosi, A. (2011). 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. Human Pathology, 42(2), 254-268. https://doi.org/10.1016/j.humpath.2010.07.004