Immune Reconstitution-Based Score for Risk Stratification of Chronic Graft-Versus-Host Disease Patients

Fabio Serpenti, Francesca Lorentino, Sarah Marktel, Raffaella Milani, Carlo Messina, Raffaella Greco, Stefania Girlanda, Daniela Clerici, Fabio Giglio, Carmine Liberatore, Francesca Farina, Sara Mastaglio, Simona Piemontese, Elena Guggiari, Francesca Lunghi, Magda Marcatti, Matteo G. Carrabba, Massimo Bernardi, Chiara Bonini, Andrea AssanelliConsuelo Corti, Jacopo Peccatori, Fabio Ciceri, Maria Teresa Lupo-Stanghellini

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Allogeneic stem cell transplantation survivors are at a relevant risk of developing chronic GvHD (cGvHD), which importantly affects quality of life and increases morbidity and mortality. Early identification of patients at risk of cGvHD-related morbidity could represent a relevant tool to tailor preventive strategies. The aim of this study was to evaluate the prognostic power of immune reconstitution (IR) at cGvHD onset through an IR-based score. Methods: We analyzed data from 411 adult patients consecutively transplanted between January 2011 and December 2016 at our Institution: 151 patients developed cGvHD (median follow-up 4 years). A first set of 111 consecutive patients with cGvHD entered the test cohort while an additional consecutive 40 patients represented the validation cohort. A Cox multivariate model for OS (overall survival) in patients with cGvHD of any severity allowed the identification of six variables independently predicting OS and TRM (transplant-related mortality). A formula for a prognostic risk index using the β coefficients derived from the model was designed. Each patient was assigned a score defining three groups of risk (low, intermediate, and high). Results: Our multivariate model defined the variables independently predicting OS at cGvHD onset: CD4+ >233 cells/mm3, NK <115 cells/mm3, IgA <0.43g/L, IgM <0.45g/L, Karnofsky PS <80%, platelets <100x103/mm3. Low-risk patients were defined as having a score ≤3.09, intermediate-risk patients >3.09 and ≤6.9, and high-risk patients >6.9. By ROC analysis, we identified a cut-off of 6.310 for both TRM and overall mortality. In the training cohort, the 6-year OS and TRM from cGvHD occurrence were 85% (95% CI, 70-92) and 13% (95% CI, 5-25) for low-risk, 64% (95% CI, 44-89) and 30% (95% CI, 15-47) for intermediate-risk, 26% (95% CI, 10-47), and 42% (95% CI, 19-63) for high-risk patients (OS p<0.0001; TRM p = 0.015). The validation cohort confirmed the model with a 6-year OS and TRM of 83% (95% CI, 48-96) and 8% (95% CI, 1-32) for low-risk, 78% (95% CI, 37-94) and 11% (95% CI, 1-41) for intermediate-risk, 37% (95% CI, 17-58), and 63% (95% CI, 36-81) for high-risk patients (OS p = 0.0075; TRM p = 0.0009). Conclusions: IR score at diagnosis of cGvHD predicts GvHD severity and overall survival. IR score may contribute to the risk stratification of patients. If confirmed in a larger and multicenter-based study, IR score could be adopted to identify patients at high risk and modulate cGvHD treatments accordingly in the context of clinical trial.

Original languageEnglish
Article number705568
JournalFrontiers in Oncology
Volume11
DOIs
Publication statusPublished - Jul 22 2021

Keywords

  • biomarker
  • chronic GvHD
  • immune reconstitution
  • overall survival
  • prognostic score

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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