Predictive Value of Liver Sitffness Measurement for Early Diagnosis of Veno-Occlusive Disease and Final Stem-Cell Outcomes

INTRODUCTION

Pre-existing comorbidities in patients undergoing allogeneic hematopoietic stem cell
transplantation (allo-HSCT) impact on its outcome. Commonly used comorbidity scores, such
as the Sorror index, recognize liver disease as a significant comorbidity but rely on analytical
liver impairment and the presence of chronic viral hepatitis, without considering other
diagnostic techniques. The aim of our study was to validate the value of liver stiffness
measurement (LSM) using Fibroscan (FS) to predict transplant outcomes and hepatic
complications in allo-HSCT recipients receiving graft-versus-host disease (GVHD) prophylaxis
with post-transplant cyclophosphamide(PTCy).

METHODS.

We conducted a single-center, prospective, observational study between October 2021 and
March 2024 to evaluate the utility of FS performed prior to transplantation and on day +14 to
predict outcomes. We elaborated ROC curves in order to identify a cut-off point for baseline FS
and day +14 FS that was predictive for the development of hepatotoxicity, hepatic veno-
occlusive disease (VOD), and acute and chronic hepatic GVHD, as well as logistic regression to
analyze the impact of FS on overall survival (OS), event-free survival (EFS), and non-relapse
mortality (NRM).

RESULTS

108 patients were included. 58% of patients were male. Median age was 58 (IQR 45-64).
Patients followed the following age modified HCT-Comorbidity Index distribution: 28% 0-2;
33% 3-4 and 29% >= 5. Thirty-two patients (30%) received myeloablative conditioning, 29
based on busulfan and 3 on total body irradiation (TBI). Donor was haploidentical in 46%
patients, matched related in 22%, matched unrelated in 27%, and 5% received a mismatched
unrelated donor graft. Stem cell source was peripheral blood in 97% of patients.
Each patient underwent at least one FS measurement (baseline 108/108; +14 84/104; both
84/104). With a median follow-up of 12.5 months, the OS and EFS at 12 months were 75% and
68%, respectively. The cumulative incidence of relapse and toxic mortality at one year were
22% and 9%, respectively. The rates of acute GVHD II-IV and hepatic acute GVHD at 180 days
were 14% and 5%, while the rates of moderate-severe chronic GVHD and hepatic chronic
GVHD were 12% and 7.4%. A total of 5 patients (4.6%) developed VOD, with a median time to
onset of 27 days.
Statistically significant differences were found in stiffness variation measured from baseline to
+14 (FSΔ) between patients who developed VOD and those who did not (p=0.048; AUROC 0.8;
0.567-1). We did not find significant differences in the median value of baseline FS and +14
between the two groups. Baseline FS, FS +14, and FSΔ were not predictive for acute and
chronic hepatic GvHD. Additionally, FS predicted HSCT outcomes in terms of OS and EFS.
Univariate logistic regression analysis identified that FS at +14 >6 Kpa as associated with worse
OS (p=0.041) and EFS (p=0.022), as well as a non-significant trend towards higher toxic
mortality (p=0.054).

DISCUSSION

In our experience in patients undergoing allo-HCT with PTCy, the dynamic evolution of FS from
baseline to day +14 is useful for predicting VOD. Furthermore, fibrosis measured by FS on day
+14 has predictive capacity for OS and EFS. Thus, it potentially becomes a prognostic factor of
interest in allo-HCT with PTCy.