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Published on: October 31, 2012
Pre-Transplant Endothelial Activation and Stress Index (EASIX) and Albumin-Modified mEASIX (mEASIX_alb) Predict
Tuba Güllü Koca1, Nizameddin Koca2, Fazıl Çağrı Hunutlu1
1Department of Hematology, Bursa Şehir Training & Research Hospital, University of Health Sciences, 16110 Bursa, Türkiye.
Background and Objectives: Endothelial dysfunction is increasingly recognized as a key determinant of transplant outcomes. The Endothelial Activation and Stress Index (EASIX), originally validated in allogeneic stem cell transplantation, integrates markers of endothelial stress into a single composite score. Its prognostic role in autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains undefined. We evaluated the pre-transplant prognostic value of EASIX, an albumin-modified formulation (mEASIX_alb), and nutritional indices (Prognostic Nutritional Index [PNI] and Controlling Nutritional Status [CONUT] score) in a large MM-ASCT cohort. Materials and Methods: We retrospectively analyzed 274 MM patients who underwent ASCT at a single institution. The pre-ASCT EASIX (LDH × Creatinine/Platelets), mEASIX_alb (LDH × Creatinine/[Platelets × Albumin]), PNI (10 × Albumin [g/dL] + 0.005 × Lymphocyte count), and CONUT score were calculated from laboratory values obtained on day 3. Optimal binary cutoffs were determined by maximally selected rank statistics. Overall survival (OS) and progression-free survival (PFS) were analyzed with Cox models in which EASIX and mEASIX_alb were entered as continuous, log-transformed variables; binary cutoffs were used only for descriptive Kaplan-Meier illustration. Internal model validity was assessed by bootstrap resampling (B = 1000). Results: Over a median follow-up of 81.3 months, 150 patients (54.7%) died, and 207 (75.5%) experienced disease progression or death. Using illustrative cutoffs (EASIX > 0.471, mEASIX_alb > 0.208, PNI < 52.29), higher EASIX was associated with shorter OS (66.7 vs. 108.1 months; p = 0.012) and PFS (27.4 vs. 42.7 months; p = 0.018). In multivariable analysis, log-transformed EASIX (HR 1.40, 95% CI 1.10-1.77; p = 0.006) and mEASIX_alb (HR 1.38, 95% CI 1.09-1.73; p = 0.007) independently predicted OS after adjustment for baseline covariates (ISS stage, pre-transplant response, and age). EASIX remained independently prognostic in a day-100 landmark analysis (HR 1.35; p = 0.023). Critically, the PNI, prognostic for OS in univariate analysis (HR 0.973; p = 0.038), did not provide independent incremental prognostic value beyond the clinical model when EASIX was added (HR 0.99; p = 0.526); this does not establish shared information between EASIX and PNI. Conclusions: Pre-transplant EASIX and mEASIX_alb are independent prognostic biomarkers in MM-ASCT. The PNI did not provide independent incremental prognostic value beyond the clinical model. These scores may inform pre-transplant risk stratification, although the illustrative cutoffs require external validation before clinical use. EASIX retained prognostic significance across transplant eras and in a cytogenetically characterized subset, supporting its era-independent and cytogenetics-independent utility.
Background and Objectives: Endothelial dysfunction is increasingly recognized as a key determinant of transplant outcomes. The Endothelial Activation and Stress Index (EASIX), originally validated in allogeneic stem cell transplantation, integrates markers of endothelial stress into a single composite score. Its prognostic role in autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains undefined. We evaluated the pre-transplant prognostic value of EASIX, an albumin-modified formulation (mEASIX_alb), and nutritional indices (Prognostic Nutritional Index [PNI] and Controlling Nutritional Status [CONUT] score) in a large MM-ASCT cohort. Materials and Methods: We retrospectively analyzed 274 MM patients who underwent ASCT at a single institution. The pre-ASCT EASIX (LDH × Creatinine/Platelets), mEASIX_alb (LDH × Creatinine/[Platelets × Albumin]), PNI (10 × Albumin [g/dL] + 0.005 × Lymphocyte count), and CONUT score were calculated from laboratory values obtained on day 3. Optimal binary cutoffs were determined by maximally selected rank statistics. Overall survival (OS) and progression-free survival (PFS) were analyzed with Cox models in which EASIX and mEASIX_alb were entered as continuous, log-transformed variables; binary cutoffs were used only for descriptive Kaplan-Meier illustration. Internal model validity was assessed by bootstrap resampling (B = 1000). Results: Over a median follow-up of 81.3 months, 150 patients (54.7%) died, and 207 (75.5%) experienced disease progression or death. Using illustrative cutoffs (EASIX > 0.471, mEASIX_alb > 0.208, PNI < 52.29), higher EASIX was associated with shorter OS (66.7 vs. 108.1 months; p = 0.012) and PFS (27.4 vs. 42.7 months; p = 0.018). In multivariable analysis, log-transformed EASIX (HR 1.40, 95% CI 1.10-1.77; p = 0.006) and mEASIX_alb (HR 1.38, 95% CI 1.09-1.73; p = 0.007) independently predicted OS after adjustment for baseline covariates (ISS stage, pre-transplant response, and age). EASIX remained independently prognostic in a day-100 landmark analysis (HR 1.35; p = 0.023). Critically, the PNI, prognostic for OS in univariate analysis (HR 0.973; p = 0.038), did not provide independent incremental prognostic value beyond the clinical model when EASIX was added (HR 0.99; p = 0.526); this does not establish shared information between EASIX and PNI. Conclusions: Pre-transplant EASIX and mEASIX_alb are independent prognostic biomarkers in MM-ASCT. The PNI did not provide independent incremental prognostic value beyond the clinical model. These scores may inform pre-transplant risk stratification, although the illustrative cutoffs require external validation before clinical use. EASIX retained prognostic significance across transplant eras and in a cytogenetically characterized subset, supporting its era-independent and cytogenetics-independent utility.