IBMTR Severity INDEX FOR GRADING ACUTE GRAFT‐VERSUS‐HOST DISEASE: RETROSPECTIVE COMPARISON WITH GLUCKSBERG GRADE

TLDR

Acute graft‑versus‑host disease severity is traditionally graded by organ‑involvement patterns and performance status using the Glucksberg system introduced 21 years ago. The study aimed to evaluate how well Glucksberg grade predicts transplant outcomes and to develop a new Severity Index that does not rely on subjective performance assessment, proposing it to improve clinical trial design and interpretation in allogeneic transplantation. The authors analyzed 2,881 sibling bone‑marrow transplant recipients, calculated relative risks of relapse, treatment‑related mortality, and treatment failure for each Glucksberg grade and organ‑involvement pattern, and used non‑T‑cell‑depleted data to construct a four‑category Severity Index based on similar risks of treatment‑related mortality and failure. Higher Glucksberg grades were associated with worse outcomes, but patients with identical grades but differing organ‑involvement patterns showed markedly different risks; the new Severity Index stratified patients into four categories (A–D) with treatment‑failure risks ranging from 0.85 to 5.69, demonstrating its prognostic utility.

Abstract

Acute graft‐versus‐host disease (GVHD) severity is graded by pattern of organ involvement and clinical performance status using a system introduced by Glucksberg and colleagues 21 years ago. We examined how well Glucksberg grade predicted transplant outcome and constructed a Severity Index not requiring subjective assessment of performance in 2881 adults receiving an HLA‐identical sibling T‐cell‐depleted ( n = 752) or non‐T‐cell‐depleted ( n = 2129) bone marrow transplant for leukaemia between 1986 and 1992. Relative risks (RR) of relapse, treatment‐related mortality (TRM) and treatment failure (TF) (relapse or death) were calculated for patients with Glucksberg Grade I, II or III/IV acute GVHD versus those without acute GVHD and for patients with distinct patterns of organ involvement regardless of Glucksberg grade. Using data for non‐T‐cell‐depleted transplants, a Severity Index was developed grouping patients with patterns of organ involvement associated with similar risks of TRM and TF. Higher Glucksberg grade predicted poorer outcome; however, patients with the same grade but different patterns of skin, liver or gut involvement often had significantly different outcomes. The revised Severity Index groups patients in four categories, A–D. PrognoStic utility of the Index was tested in patients receiving T‐cell‐depleted transplants; similar RRs of TF were observed. Compared to patients without acute GVHD, RRs (95% confidence interval) of TF were 0.85 (0.69, 1.05) for patients with Index A, 1.21 (1.02, 1.43) with B, 2.19 (1.78, 2.71) with C, and 5.69 (4.57, 7.08) with D. An acute GVHD Severity Index is proposed to enhance design and interpretation of clinical trials in the current era of allogeneic blood and bone marrow transplantation.