---
title: "Lactate dehydrogenase-to-albumin ratio at aGVHD diagnosis predicts mortality after allo‑HSCT"
id: "frontiers-in-immunology-10-association-of-the-lactate-dehydrogenase-to-albumin-ratio-with-all-cause-and"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-10-association-of-the-lactate-dehydrogenase-to-albumin-ratio-with-all-cause-and"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936503"
published_at: "2026-10-09T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Lactate dehydrogenase-to-albumin ratio at aGVHD diagnosis predicts mortality after allo‑HSCT
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-10-association-of-the-lactate-dehydrogenase-to-albumin-ratio-with-all-cause-and
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1936503)
- **Published At:** 2026-10-09T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This single-center retrospective cohort evaluated the prognostic value of the **lactate dehydrogenase-to-albumin ratio (LAR)** measured at acute graft-versus-host disease (**aGVHD**) diagnosis in 109 allo-HSCT recipients (2019–2024). - Patients were stratified into LAR tertiles (T1: 4.37–8.84; T2: 8.84–16.02; T3: 16.02–178.02); LAR was also analyzed as a natural-log-transformed continuous variable (ln-LAR). - Over a median follow-up of 30 months, 69 all-cause mortality (**ACM**) events (63.3%) and 66 non-relapse mortality (**NRM**) events (60.6%) occurred. - In fully adjusted Cox models (Model 3), continuous **ln-LAR** independently predicted ACM (HR 1.73, 95% CI 1.07–2.77, P = 0.024) and NRM (HR 1.69, 95% CI 1.03–2.77, P = 0.038). - Patients in the highest LAR tertile (T3) had 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). - Restricted cubic spline (RCS) analyses showed nonlinear inverted-L dose-response patterns with threshold breakpoints estimated near LAR ≈53 for ACM and ≈19 for NRM; nonlinearity reached statistical significance. - Subgroup and interaction analyses identified no significant effect modifiers (all P for interaction >0.05). Sensitivity analyses excluding early deaths (<3 months) produced consistent findings with amplified effect sizes. - Baseline differences across LAR tertiles included progressively higher proportion of grade III–IV aGVHD (T1 22.2% → T3 81.1%), higher creatinine and BUN, higher AST, and greater CMV viremia in higher LAR groups. - Authors conclude elevated **LAR** at aGVHD diagnosis is independently associated with higher ACM and NRM; findings are hypothesis-generating and require external validation in independent cohorts.
## Clinical Analysis & Structured Key Points
Frontiers | 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 0.05), and sensitivity analyses excluding early deaths yielded consistent results with amplified effect sizes.ConclusionElevated 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."> ORIGINAL RESEARCH article Front. Immunol. , 09 October 2026 Sec. Alloimmunity and Transplantation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1936503 Published in Frontiers in Immunology Alloimmunity and Transplantation 7 impact factor 11.3 citescore Editor & Reviewers Edited by E K Emmanuel Katsanis Reviewed by P G Panagiotis G. Asteris H J Hongfeng Jiang Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Table 1 The baseline characteristics and demographic characteristics of the study population by categories of LAR. View in article Table 2 Association between LAR and ACM and NRM in patients with aGVHD following allo-HSCT. View in article ORIGINAL RESEARCH article Front. Immunol. , 09 October 2026 Sec. Alloimmunity and Transplantation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1936503 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 G L Gangping Li 1 D Z Di Zhang 2 F Y Fangfang Yuan 1 M L Minghui Li 1 Y W Yongqi Wang 1 J Z Jian Zhou 1 Y F Yuewen Fu 1 * 1. Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China 2. Department of Medical Records Management, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China Article metrics View details 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. Introduction Allogeneic hematopoietic stem cell transplantation (allo-HSCT) constitutes a potentially curative therapeutic modality for a spectrum of hematologic malignancies, bone marrow failure syndromes, and selected non-malignant disorders ( 1 – 3 ). Substantial advances in donor selection, conditioning regimens, graft-versus-host disease (GVHD) prophylaxis, and supportive care have progressively expanded the applicability of this procedure to older and medically complex patient population ( 4 , 5 ). Despite these refinements, transplant-related morbidity and mortality remain substantial, with acute graft-versus-host disease (aGVHD) representing one of the most formidable obstacles to favorable outcomes ( 6 , 7 ). aGVHD, primarily mediated by donor T-cell recognition of host alloantigens, triggers a complex inflammatory cascade culminating in target organ damage involving the skin, liver, and gastrointestinal tract ( 6 ). The clinical trajectory of aGVHD is highly variable; whereas some patients respond satisfactorily to first-line corticosteroid therapy, a substantial proportion progress to steroid-refractory disease, which portends an exceedingly poor prognosis with mortality rates exceeding 50% ( 8 , 9 ). Accurate risk stratification at the onset of aGVHD is critical for guiding treatment intensity, facilitating early intervention, and ultimately improving survival. However, current prognostic assessment relies predominantly on clinical parameters—including aGVHD grade, organ involvement, and response to initial therapy—that capture only a fraction of the underlying biological heterogeneity ( 10 , 11 ). In response to this limitation, considerable investigative effort has been directed toward identifying circulating biomarkers that reflect the pathophysiologic processes driving aGVHD. The Mount Sinai Acute GVHD International Consortium (MAGIC) has established a panel comprising suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3-α (REG3α), which robustly predicts treatment response and non-relapse mortality ( 12 , 13 ). Additional candidate biomarkers, including tumor necrosis factor receptor 1 (TNFR1), elafin, and interleukin-2 receptor α, have demonstrated association with aGVHD severity and outcomes ( 14 , 15 ). Despite these advances, many of these assays require specialized platforms and are not routinely available in most clinical laboratories, highlighting the need for accessible, low-cost biomarkers that can be derived from standard laboratory data. Serum lactate dehydrogenase (LDH) is a ubiquitous intracellular enzyme catalyzing the interconversion of lactate and pyruvate; its elevation in the circulation reliably reflects cellular turnover, tissue hypoxia, and metabolic stress ( 16 , 17 ). A comprehensive meta-analysis of 68 studies encompassing 31,857 patients with solid tumors confirmed that elevated LDH is associated with a 48% increased risk of death (HR 1.48, 95% CI 1.43–1.53), establishing LDH as a robust prognostic biomarker across multiple malignancies ( 16 ). Elevated LDH has also been consistently associated with adverse outcomes in the peri-transplant setting ( 18 – 20 ). Specifically, pre-transplant hyper-LDH predicts inferior overall survival and higher relapse incidence in patients with acute myeloid leukemia and lymphoma undergoing allo-HSCT ( 21 , 22 ). Serum albumin, conversely, serves as a proxy for nutritional reserve and systemic inflammatory burden; hypoalbuminemia has been linked to increased non-relapse mortality in patients with lower gastrointestinal aGVHD ( 23 ). Composite inflammatory and nutritional indices, such as the C-reactive protein-to-albumin ratio, have demonstrated prognostic utility in allo-HSCT recipients ( 24 , 25 ). The lactate dehydrogenase to albumin ratio (LAR), which integrates the metabolic dimension captured by LDH with the nutritional-inflammatory dimension reflected by albumin, has emerged as a promising prognostic biomarker across multiple solid tumor types ( 26 – 29 ). A recent meta-analysis encompassing over 8,000 patients confirmed that elevated pretreatment LAR is significantly associated with inferior overall survival (HR 2.02, 95% CI 1.74–2.34) and progression-free survival in malignancies ( 30 ). However, the prognostic value of LAR in the specific context of aGVHD following allo-HSCT has not been systematically investigated. Accordingly, this study aimed to evaluate the association between LAR, measured at the time of aGVHD diagnosis, and all-cause mortality (ACM) and non-relapse mortality (NRM) in patients undergoing allo-HSCT. The remainder of this article is structured as follows. Section 2 (Methods) describes the study population, the definitions of LAR and the outcomes, and the statistical analyses, including restricted cubic spline and threshold analyses. Section 3 (Results) reports the association of LAR with all-cause and non-relapse mortality across tertiles and strata. Sections 4 and 5 present the discussion of the findings in the context of existing evidence, the study limitations, and our conclusions. Methods Patients and study design This retrospective cohort study consecutively enrolled patients undergoing allo-HSCT at Henan Cancer Hospital between January 2019 and December 2024. Within this transplant cohort, patients who developed aGVHD were identified according to established clinical and histopathological diagnostic criteria ( 1 ). Exclusion criteria comprised: (1) had active, uncontrolled infection at aGVHD onset; (2) incomplete LDH or albumin measurements within 48 hours of aGVHD diagnosis; (3) loss to follow-up prior to study completion. The final analytical cohort comprised 109 patients. The study protocol was approved by the Research Ethics Committee of Henan Cancer Hospital (registration number: 2026-304-001), and all participants provided written informed consent. All procedures were conducted in accordance with the Declaration of Helsinki. Conditioning regimens and GVHD prophylaxis Transplantation conditioning intensity was classified as myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC) according to established consensus criteria ( 29 – 31 ). MAC regimens included busulfan combined with cyclophosphamide (Bu/Cy) or total body irradiation combined with cyclophosphamide (TBI/Cy). RIC regimens predominantly comprised fludarabine combined with busulfan (Flu/Bu, busulfan ≤6.4 mg/kg) or fludarabine combined with melphalan (Flu/Mel). For patients receiving grafts from unrelated or haploidentical donors, conditioning incorporated anti-human thymocyte immunoglobulin (ATG, 2.5 mg/kg/day for 3–4 days) for in vivo T-cell depletion, whereas sibling donor transplants proceeded without ATG. GVHD prophylaxis consisted of a calcineurin inhibitor (cyclosporine A, targeted trough 200–400 ng/mL, or tacrolimus, targeted trough 5–15 ng/mL) combined with methotrexate (15 mg/m² on day +1, 10 mg/m² on days +3, +6, and +11) and mycophenolate mofetil (MMF, 500–1000 mg every 12 hours from day −3 to day +30, tapered thereafter). Stem cell sources included peripheral blood stem cells (PBSC), bone marrow (BM), or a combination thereof. Supportive care All transplant recipients received standardized supportive care according to institutional protocols. Antiviral prophylaxis consisted of ganciclovir (5 mg/kg intravenously every 12 hours) or valganciclovir, initiated upon neutrophil engraftment, with preemptive monitoring for cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia by quantitative polymerase chain reaction twice weekly through day +100, followed by weekly monitoring thereafter. Antifungal prophylaxis comprised posaconazole suspension (200 mg three times daily) or voriconazole (200 mg twice daily, with therapeutic drug monitoring). Pneumocystis jirovecii prophylaxis was administered with sulfamethoxazole-trimethoprim (800/160 mg twice daily, three times weekly) from engraftment until immunosuppression discontinuation. Phenytoin (5 mg/kg/day) was administered for seizure prophylaxis during busulfan conditioning. Mesna (equivalent to 80–120% of cyclophosphamide dose) was employed for hemorrhagic cystitis prevention. Ursodeoxycholic acid (300 mg twice daily) was administered for hepatobiliary protection. Blood products were leukoreduced, irradiated, and CMV-seronegative where indicated. Febrile neutropenia was managed empirically with broad-spectrum antibiotics per institutional guidelines, with subsequent de-escalation guided by microbiologic culture results. LAR measurement and data collection The lactate dehydrogenase to albumin ratio (LAR) was calculated as serum LDH activity (U/L) divided by serum albumin concentration (g/L) ( 26 – 29 ), measured within 48 hours of aGVHD diagnosis. For regression analyses, LAR values were natural-log transformed (ln-LAR) to reduce skewness and improve model fit. Serum LDH activity was determined using the lactate-to-pyruvate enzymatic reduction method on a Beckman Coulter AU5800 clinical chemistry analyzer (Beckman Coulter, Brea, CA, USA). Serum albumin was quantified using the bromocresol green dye-binding method on the same platform. Comprehensive demographic, clinical, and laboratory parameters were abstracted from electronic medical records, including: age, sex, indication for HSCT, stem cell source, transplant type (matched sibling, unrelated, haploidentical), conditioning regimen intensity (MAC vs RIC), ABO compatibility, mononuclear cell (MNC) count, CD34+ cell count, interval from transplantation to aGVHD diagnosis, aGVHD grade (I–II vs III–IV), neutrophil engraftment time, CMV viremia, EBV viremia, complete blood count, liver and renal function parameters, and infectious complications. Outcomes The primary endpoint was all-cause mortality (ACM), defined as death from any cause during the follow-up period. The secondary endpoint was non-relapse mortality (NRM), defined as death without preceding disease relapse or progression. Follow-up duration was calculated from the date of aGVHD diagnosis to death or last contact, with administrative censoring on December 31, 2024. Survival status was ascertained through outpatient clinic records, hospital information systems, and telephone follow-up. Statistical analysis Normality of variable distributions was evaluated through histogram inspection, quantile-quantile plots, and the Kolmogorov-Smirnov test. Continuous variables following a normal distribution were reported as means with standard deviations (mean ± SD), whereas non-normally distributed variables were summarized as medians with interquartile ranges (median [IQR]). Categorical variables were expressed as frequencies with percentages. Between-group comparisons were performed using analysis of variance (ANOVA) for normally distributed continuous variables, the Kruskal-Wallis test for skewed continuous variables, and Pearson’s chi-square or Fisher’s exact tests for categorical variables, as appropriate. The association between natural-log-transformed LAR (ln-LAR) and mortality endpoints was quantified using Cox proportional hazards regression models, with results reported as hazard ratios (HR) accompanied by 95% confidence intervals (CI). The proportional hazards assumption was verified through log-log survival plots and examination of time-dependent covariate interactions. Missing data at the aGVHD diagnosis time point (LDH, albumin, and other covariates) were assessed; all 109 included patients had complete LDH and albumin values required to compute LAR, as patients with incomplete measurements were excluded before enrollment. No imputation was performed; complete-case analysis was applied in all primary models, and the numbers of patients and events in each model are reported in the corresponding table. Three sequential Cox regression models were developed: Model 1 adjusted for demographic factors (age, sex); Model 2 incorporated Model 1 covariates plus transplantation parameters (indication for HSCT, stem cell source, transplant type, conditioning regimen, interval from transplantation to aGVHD diagnosis, ABO compatibility, MNC count, and CD34+ cell count); Model 3 expanded Model 2 with post-transplant clinical covariates (neutrophil engraftment time, CMV viremia, EBV viremia, white blood cell count, hemoglobin, platelet count, total bilirubin, creatinine, pulmonary infection, intestinal infection, febrile neutropenia). Restricted cubic spline (RCS) regression with three knots positioned at the 10th, 50th, and 90th percentiles characterized the dose-response profile. A two-piecewise Cox regression model identified potential threshold effects, with breakpoints determined by maximum likelihood estimation. Prior to the two-piecewise Cox breakpoint estimation, natural-log-transformed LAR values were screened with Grubbs’ test (two-sided, α = 0.05). One outlier was identified and excluded for the ACM analysis (N = 108) and one for the NRM analysis (N = 108), preventing extreme LAR values from dominating the segmented fit; these patients remained in the primary Cox analyses. Kaplan-Meier survival curves stratified by LAR tertiles were generated, and between-group survival differences were assessed using the log-rank test. Subgroup and interaction analyses were performed across clinically relevant strata. Sensitivity analyses excluding patients with survival duration 0.05). Figure 1 Study flow diagram of cohort derivation. Among 521 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2019 and December 2024, 116 developed acute graft-versus-host disease (aGVHD). Afte
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