Refined hepatic grading system in chronic graft-versus-host disease improves prognostic risk stratification of long-term outcomes

Eur J Haematol. 2021 Apr;106(4):508-519. doi: 10.1111/ejh.13576. Epub 2021 Jan 25.

Abstract

Objectives: Hepatic grading systems for categorizing severity in chronic graft-versus-host disease (cGvHD) were determined arbitrarily, leading us to initiate the present study to provide objective evidence for the determination of optimal cutoff values and devise a hepatic grading system to predict prognosis.

Methods: Of 842 patients who received allogeneic hematopoietic stem transplant (HCT), 336 patients diagnosed with cGvHD were evaluated for overall survival (OS) and non-relapse mortality (NRM) after cGVHD development. Multiple statistical parameters were evaluated to define optimal cutoff values of liver profile, including negative predictive value (NPV), positive predictive value (PPV), accuracy, and p-values as measures of risk stratification power.

Results: We found that alkaline phosphatase (ALP) ≥ 146 IU/L (NPV: 83.4%; PPV: 32.8%; accuracy: 52.7%) and bilirubin ≥ 14 µmol/L (NPV: 81.8%; PPV: 39.4%; accuracy 68.1%) significantly correlated with OS. We developed a refined hepatic cGvHD grading score (RHS), stratifying patients into a low-RHS group with RHS score 0, OS at 3 years (n = 162) to 80.5%, compared to high-RHS group with score 1-2 (n = 172) 62.7%. Regarding NRM, score 0 segregated NRM at 3 years to 11.9%, compared with score 1-2 19.6%, P = .1.

Conclusions: Refined hepatic score is promising for stratifying patients with cGVHD and liver involvement according to long-term outcomes.

Keywords: hematopoietic stem cell transplantation; liver graft-versus-host disease; transplantation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chronic Disease
  • Disease Management
  • Disease Susceptibility
  • Female
  • Graft vs Host Disease / diagnosis*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality*
  • Graft vs Host Disease / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Severity of Illness Index
  • Transplantation Conditioning
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult