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4869 Incidence, Clinical Risk Factors, and Biomarkers of SOS/VOD Following Allogeneic HSCT in Adults: A Real-Life Study By the Spanish Group of Hematopoietic Stem Cell Transplantation and Cell Therapy (GETH-TC)

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster III
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Supportive Care, Treatment Considerations, Adverse Events
Monday, December 9, 2024, 6:00 PM-8:00 PM

Ariadna Pérez1*, Monica Cabrero Calvo, MD2*, Juan Montoro, MD, PhD3*, Miriam Sanchez-Escamilla4*, Maria Angeles Cuesta5*, Valle Gomez G De Soria, MD6*, Pedro Gonzalez-Sierra7*, Karem Humala8*, Oriana López Godino9*, Maria Luisa Palacios-Berraquero10*, Lucía López-Corral11*, Jaime Sanz12*, Maria Jesus Pascual13*, Jose Luis Piñana, MD, PhD14*, Arancha Bermúdez15*, José Mª Bellón16*, Silvia Filaferro17*, Guillermo Orti, MD, PhD18*, Pascual Balsalobre19* and Carlos Solano, MD, PhD20

1Hematology Department, Hospital Clínico de Valencia, Valencia, Spain
2Hospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain
3Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
4Hematology Dpt., Hospital Univ. Marqués de Valdecilla, Santander, Spain
5Hematology Dpt., Hospital Regional Universitario de Málaga, Malaga, ESP
6Hospital Universitario La Princesa, Madrid, Spain
7Hematology Department, Hospital Universitario Virgen de las Nieves de Granada, Granada, ESP
8Hematology Dpt., Hospital Universitario La Paz, Madrid, ESP
9Hematology Dpt., Hospital Univ. Morales Meseguer, Murcia, Spain
10Hospital Univ. Ramón y Cajal, Madrid, Spain
11University Hospital of Salamanca, Salamanca, Spain
12Hematology Department, Hospital Universitari i Politècnic La Fe, VALENCIA, ESP
13Hospital Regional Universitario de Málaga, Malaga, Spain
14Servicio de Hematología, Hospital Clínico Universitario de Valencia, Valencia, Spain
15Hospital Marques de Valdecilla (IDIVAL), Santander, Spain
16Biostatistics, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain
17Grupo Español de Trasplante de Progenitores Hematopoyéticos y Terapia Celular (GETH-TC) Data Office, Madrid, Spain
18Vall D' Hebron University Hospital, Barcelona, Spain
19Grupo Español de Trasplante de Progenitores Hematopoyéticos y Terapia Celular (GETH-TC), Madrid, AL, Spain
20Hematology Department, Hematology Department, Hospital Clínico Universitario-INCLIVA, Valencia, Spain

Introduction

Sinusoidal obstruction syndrome (SOS) or hepatic veno-occlusive disease (VOD) is a serious complication following hematopoietic stem cell transplantation (HSCT) with an overall incidence ranging from 5% to 15% and a highly variable mortality rate. Recently, the European Society for Blood and Marrow Transplantation (EBMT) updated the diagnostic criteria, severity assessments, and risk factor evaluations for SOS/VOD (Mohty M et al. 2023). The EASIX score, a biomarker of endothelial dysfunction, has been associated to the incidence of SOS/VOD, overall survival (OS), and non-relapse mortality (NRM) following Allo-HSCT (Jiang S, et al. 2021), potentially aiding in early intervention. This study aims to analyze the incidence and impact of clinical risk factors and the EASIX score on Allo-HSCT outcomes in a large real-world, registry-based cohort.

Patients and methods

This multicenter, retrospective observational registry study included all consecutive Allo-HSCT procedures performed between Jan-2019 and Dec-2020 across nine centers members of GETH-TC. All patients (pts) had a minimum follow-up of one year. SOS/VOD definition and clinical risk factors analysis were assessed according to the EBMT-2023 guidelines. The EASIX score was calculated at three time-points after Allo-HSCT (EASIX-d0, d+7, d+14). Different cut-off points for EASIX were evaluated for their predictive ability using Cox regression and Harrell's C test. Statistical analysis were conducted using the Stata software package.

Results

A total of 796 adult pts (aged >18 yo) were included, with the following characteristics: median age of 53.7 years (range 18-74), male gender 59%. Most pts were undergoing their first Allo-HSCT (80%) and used peripheral blood as stem cell source (84%), with AML/MDS being the most frequent underlying diagnosis (67%). Donor types included: matched related donor (35%), haploidentical (33%) and matched unrelated donor (23%). Conditioning intensity: RIC (58%); MAC: (42%). SOS/VOD developed in 81 pts (10.2%), at a median time (IQR) of 15 (9-26) days. Probable SOS/VOD occurred in 41 pts (50.6%), clinical in 36 (44.4%), and proven in 4 (4.9%). The cumulative incidence of SOS/VOD at 30 and 90 days post-HSCT was 8.56% (95% CI, 6.75 -10.64) and 10.20 (95% CI, 8.22-12.43), respectively. Defibrotide was used in 45 pts (55.6%).

At a median follow-up of 35 months, OS and NRM of the entire cohort were 61.89% (95% CI, 58.40-65.19) and 24.10% (95% CI, 21.17-27.14), respectively. OS and NRM for patients developing and not developing SOS/VOD were 50.54% (95% CI, 38.26-61.59) vs. 65.8% (95% CI, 62.17-69.16), p=.085 and 33.42% (95% CI, 23.42-43.71) vs. 18.56% (95% CI, 15.80-21.49), p=.003, respectively

The D+90 cumulative incidence of SOS/VOD-related mortality was 1.52% (0.83-2.57) for the whole series and 15% (8.23-23.67) for pts developing SOS/VOD.

Univariate analysis identified significant clinical risk factors for SOS/VOD diagnosis, including advanced disease (≥2nd CR or relapse) (p=.026), non-HLA-matched donor (p=.016), ≥2nd HSCT (p<.0001), use of parenteral nutrition (p<.0001), elevated serum bilirubin (> 1.5 mg/dL/>26 μmol/L) (p=.034), prior use of gemtuzumab ozogamicin or inotuzumab ozogamicin (p=0.037), elevated levels of tacrolimus/sirolimus (>10 ng/mL) (p=.003) or INR (>1.5) (<.0001) before SOS/VOD diagnosis, baseline (d0) EASIX ≥2 (p= .032) and EASIX ≥ 6 on d+7 (p <.001) and on d+14 (p <.001). Patients with SOS/VOD showed an increased risk of NRM (sHR 1.95, p=.003)

Multivariate analysis confirmed the prognostic value (sHR) for SOS/VOD incidence of d0 EASIX ≥2 (1.60), d+7 EASIX ≥6 (2.62), d+14 EASIX ≥6 (2.77) adjusted by >1st HSCT, parenteral nutrition, elevated serum bilirubin, prior gemtuzumab use, elevated levels of tacrolimus/sirolimus, and elevated INR.

Conclusions

This large, registry-based multicenter retrospective study observed a SOS/VOD incidence similar to other series, with a significant impact on NRM. The prognostic factors analysis confirmed not only several high-risk factors included in the EBMT classification, such as second or subsequent HSCT and the use of parenteral nutrition, but also other less well stablished risk factors, including elevated tacrolimus/sirolimus or INR levels. EASIX score at d0, d+7 and d+14, was validated as predictor of SOS/VOD onset. These findings warrant confirmation in a prospective study.

Disclosures: Cabrero Calvo: Jazz Pharmaceuticals: Honoraria, Research Funding. Palacios-Berraquero: Gilead-Kite: Speakers Bureau. Orti: Sanofi: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Jazz: Honoraria; Incyte: Honoraria, Research Funding. Balsalobre: Gilead-Kite: Ended employment in the past 24 months.

*signifies non-member of ASH