Cardiovascular

Pre-Transplant Endothelial Activation and Stress Index (EASIX) and Albumin-Modified mEASIX (mEASIX_alb) Predict Survival in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

TL;DR

Pre-transplant EASIX and mEASIX_alb are independent prognostic biomarkers for overall survival and progression-free survival in multiple myeloma patients undergoing autologous stem cell transplantation, while PNI did not provide independent incremental prognostic value beyond the clinical model.

Key Findings

Higher pre-transplant EASIX was associated with significantly shorter overall survival and progression-free survival in MM-ASCT patients.

  • Using an illustrative cutoff of EASIX > 0.471, median OS was 66.7 months vs. 108.1 months in the low-EASIX group (p = 0.012)
  • Median PFS was 27.4 months vs. 42.7 months for high vs. low EASIX groups (p = 0.018)
  • Over a median follow-up of 81.3 months, 150 patients (54.7%) died and 207 (75.5%) experienced disease progression or death
  • The cohort comprised 274 MM patients who underwent ASCT at a single institution, analyzed retrospectively

Log-transformed EASIX independently predicted overall survival in multivariable analysis after adjustment for baseline covariates.

  • HR 1.40, 95% CI 1.10–1.77; p = 0.006 for OS in multivariable Cox model
  • Covariates adjusted for included ISS stage, pre-transplant response, and age
  • EASIX was entered as a continuous, log-transformed variable in Cox models; binary cutoffs were used only for descriptive Kaplan-Meier illustration
  • Internal model validity was assessed by bootstrap resampling (B = 1000)

The albumin-modified formulation mEASIX_alb independently predicted overall survival in multivariable analysis.

  • HR 1.38, 95% CI 1.09–1.73; p = 0.007 for OS in multivariable analysis
  • mEASIX_alb was calculated as LDH × Creatinine / (Platelets × Albumin)
  • Illustrative cutoff for mEASIX_alb was > 0.208
  • Optimal binary cutoffs for all indices were determined by maximally selected rank statistics

EASIX retained independent prognostic significance in a day-100 landmark analysis.

  • HR 1.35; p = 0.023 in the day-100 landmark analysis
  • This analysis helps address potential immortal time bias and confirms prognostic utility beyond the early post-transplant period
  • EASIX retained prognostic significance across transplant eras and in a cytogenetically characterized subset, supporting era-independent and cytogenetics-independent utility

The Prognostic Nutritional Index (PNI) was prognostic for OS in univariate analysis but did not provide independent incremental prognostic value beyond the clinical model when EASIX was added.

  • PNI HR 0.973 in univariate analysis; p = 0.038, using a cutoff of PNI < 52.29
  • When EASIX was included in the multivariable model, PNI HR became 0.99; p = 0.526
  • The authors note this finding 'does not establish shared information between EASIX and PNI'
  • PNI was calculated as 10 × Albumin (g/dL) + 0.005 × Lymphocyte count

The CONUT score did not demonstrate independent prognostic value in the multivariable models.

  • Both PNI and CONUT score were evaluated as nutritional indices alongside EASIX and mEASIX_alb
  • Laboratory values were obtained on day −3 (pre-transplant day 3)
  • CONUT score is a nutritional assessment tool calculated from albumin, total cholesterol, and lymphocyte count

Pre-transplant EASIX was calculated using a formula integrating three markers of endothelial stress and organ function.

  • EASIX formula: LDH × Creatinine / Platelets
  • EASIX was originally validated in allogeneic stem cell transplantation; this study evaluated its role in autologous SCT for MM
  • Laboratory values were obtained on day −3 relative to transplant
  • The study is retrospective, single-institution, with 274 patients

What This Means

This research suggests that a simple blood test score called EASIX (Endothelial Activation and Stress Index), calculated before a stem cell transplant, can help predict how well multiple myeloma patients will do after their transplant. EASIX combines three routine lab values — LDH (a marker of cell damage), creatinine (a kidney function marker), and platelet count — into a single number. In a group of 274 patients followed for nearly seven years on average, those with higher EASIX scores before transplant had notably shorter survival times and shorter periods without disease progression compared to those with lower scores. A modified version of the score that also incorporates albumin (a protein reflecting nutritional status), called mEASIX_alb, showed similarly strong predictive ability. The study also tested two nutritional scoring systems — the Prognostic Nutritional Index (PNI) and the CONUT score — to see if nutrition-based measures could predict outcomes. While PNI showed some predictive value on its own, it lost its independent significance once EASIX was included in the statistical model, suggesting that EASIX may capture more comprehensive risk information. Importantly, EASIX remained a significant predictor even in analyses that accounted for time after transplant and in patient subgroups defined by chromosome abnormalities, suggesting its usefulness is broad and not limited to specific eras of treatment or genetic risk groups. This research suggests that measuring EASIX before an autologous stem cell transplant could help doctors identify multiple myeloma patients at higher risk of poor outcomes, potentially allowing for more personalized monitoring or treatment planning. However, the specific score thresholds identified in this study would need to be confirmed in other patient populations before being used in routine clinical practice.

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Citation

G&#xfc;ll&#xfc; Koca T, Koca N, Hunutlu F, &#xc7;ubuk&#xe7;u S, Y&#x131;lmaz R, Ersal T, et al.. (2026). Pre-Transplant Endothelial Activation and Stress Index (EASIX) and Albumin-Modified mEASIX (mEASIX_alb) Predict Survival in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.. Medicina (Kaunas, Lithuania). https://doi.org/10.3390/medicina62081572