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Peer-reviewedCC BY 4.0Frontiers in Immunology

Association of the lactate dehydrogenase-to-albumin ratio with all-cause and non-relapse mortality in patients with aGVHD after allogeneic HSCT: a single-center retrospective cohort study

  • Gangping Li1
  • Di Zhang2
  • Fangfang Yuan1
  • Minghui Li1
  • Yongqi Wang1
  • Jian Zhou1
  • Yuewen Fu1
  1. 1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
  2. 2Department of Medical Records Management, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital
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Abstract

Background: Acute graft-versus-host disease (aGVHD) remains a leading cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The lactate dehydrogenase-to-albumin ratio (LAR), integrating metabolic stress and nutritional reserve, has demonstrated prognostic value across malignancies but has not been investigated in aGVHD. We evaluated the association between LAR measured at aGVHD diagnosis and both all-cause mortality (ACM) and non-relapse mortality (NRM).

Methods: This retrospective cohort study enrolled 109 consecutive allo-HSCT recipients who developed aGVHD at Henan Cancer Hospital (2019–2024). Patients were stratified by LAR tertiles (T1:4.37–8.84;T2:8.84–16.02;T3:16.02–178.02).Natural-log-transformed LAR (ln-LAR) was analyzed using Cox proportional hazards models with three hierarchical adjustments: Model 1 (age, sex), Model 2 (+transplantation covariates), and Model 3 (+post-transplant clinical covariates). Restricted cubic spline regression and two-piecewise threshold analyses characterized dose-response relationships. Subgroup, interaction, and sensitivity analyses were performed to evaluate the robustness.

Results: Over a median follow-up of 30 months, 69 ACM (63.3%) and 66 NRM (60.6%) events occurred among 109 patients (mean age 29.4 ± 15.3 years, 62.4% male; 51 grade I–II, 58 grade III–IV aGVHD). Continuous ln-LAR independently predicted ACM (Model 3: HR 1.73, 95% CI 1.07–2.77, P = 0.024) and NRM (Model 3: HR 1.69, 95% CI 1.03–2.77, P = 0.038). The highest tertile (T3) conferred approximately three-fold higher risk versus T1 (ACM: HR 2.96, 95% CI 1.27–6.90, P = 0.012; NRM: HR 3.25, 95% CI 1.36–7.74, P = 0.008). RCS demonstrated nonlinear inverted-L patterns (nonlinearity P = 0.006 for ACM, P = 0.009 for NRM) with threshold effects at LAR≈53 and ≈19, respectively. Subgroup and interaction analyses revealed no significant modifiers (all P for interaction >0.05), and sensitivity analyses excluding early deaths yielded consistent results with amplified effect sizes.

Conclusion: Elevated LAR at aGVHD diagnosis was independently associated with higher all-cause and non-relapse mortality in this cohort. These findings are hypothesis-generating; the clinical utility of LAR requires external validation in independent cohorts.

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BibTeXRIS
BibTeX
@article{li2026association,
  title = {{Association of the lactate dehydrogenase-to-albumin ratio with all-cause and non-relapse mortality in patients with aGVHD after allogeneic HSCT: a single-center retrospective cohort study}},
  author = {Gangping Li and Di Zhang and Fangfang Yuan and Minghui Li and Yongqi Wang and Jian Zhou and Yuewen Fu},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1936503},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936503/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Association of the lactate dehydrogenase-to-albumin ratio with all-cause and non-relapse mortality in patients with aGVHD after allogeneic HSCT: a single-center retrospective cohort study
AU  - Gangping Li
AU  - Di Zhang
AU  - Fangfang Yuan
AU  - Minghui Li
AU  - Yongqi Wang
AU  - Jian Zhou
AU  - Yuewen Fu
PY  - 2026
DA  - 2026/10/09
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1936503
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936503/full
AB  - Background: Acute graft-versus-host disease (aGVHD) remains a leading cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The lactate dehydrogenase-to-albumin ratio (LAR), integrating metabolic stress and nutritional reserve, has demonstrated prognostic value across malignancies but has not been investigated in aGVHD. We evaluated the association between LAR measured at aGVHD diagnosis and both all-cause mortality (ACM) and non-relapse mortality (NRM).  Methods: This retrospective cohort study enrolled 109 consecutive allo-HSCT recipients who developed aGVHD at Henan Cancer Hospital (2019–2024). Patients were stratified by LAR tertiles (T1:4.37–8.84;T2:8.84–16.02;T3:16.02–178.02).Natural-log-transformed LAR (ln-LAR) was analyzed using Cox proportional hazards models with three hierarchical adjustments: Model 1 (age, sex), Model 2 (+transplantation covariates), and Model 3 (+post-transplant clinical covariates). Restricted cubic spline regression and two-piecewise threshold analyses characterized dose-response relationships. Subgroup, interaction, and sensitivity analyses were performed to evaluate the robustness.  Results: Over a median follow-up of 30 months, 69 ACM (63.3%) and 66 NRM (60.6%) events occurred among 109 patients (mean age 29.4 ± 15.3 years, 62.4% male; 51 grade I–II, 58 grade III–IV aGVHD). Continuous ln-LAR independently predicted ACM (Model 3: HR 1.73, 95% CI 1.07–2.77, P = 0.024) and NRM (Model 3: HR 1.69, 95% CI 1.03–2.77, P = 0.038). The highest tertile (T3) conferred approximately three-fold higher risk versus T1 (ACM: HR 2.96, 95% CI 1.27–6.90, P = 0.012; NRM: HR 3.25, 95% CI 1.36–7.74, P = 0.008). RCS demonstrated nonlinear inverted-L patterns (nonlinearity P = 0.006 for ACM, P = 0.009 for NRM) with threshold effects at LAR≈53 and ≈19, respectively. Subgroup and interaction analyses revealed no significant modifiers (all P for interaction >0.05), and sensitivity analyses excluding early deaths yielded consistent results with amplified effect sizes.  Conclusion: Elevated LAR at aGVHD diagnosis was independently associated with higher all-cause and non-relapse mortality in this cohort. These findings are hypothesis-generating; the clinical utility of LAR requires external validation in independent cohorts.
SN  - 1664-3224
ER  -