Suresh, A.

Abstract Rationale: Hematopoietic cell transplantation (HCT) risk scores have seen minimal updates over the past 20 years, despite advancements in clinical practice. Pulmonary function test (PFT) thresholds, initially based on NHANES reference equations, now have alternative reference standards from the Global Lung Function Initiative (GLI) 2012 and GLI-Global, which may reclassify patients and affect outcomes. This study investigates the impact of GLI reclassification on outcomes in HCT, comparing traditional fixed thresholds with continuous (z-score) risk assessment models. Methods: A retrospective review of 3,120 adult patients who underwent autologous HCT at MD Anderson Cancer Center from 1999 to 2015 was conducted. Primary endpoints were ICU admission, mechanical ventilation (IMV), and survival within 120 days post-transplant. PFT measures (FEV1, FVC, DLCO) were calculated using GLI-2012 and GLI-Global reference equations, analyzed both continuously (z-scores) and categorically by ATS/ERS guidelines. Cox proportional hazards and logistic regression models were employed, with AUROC comparisons to evaluate predictive performance. Results: The cohort had a mean age of 49 years (SD 14), with 41% female and 77% White. Of the 3,120 patients included in the study, the cohort consisted of 77% White, 5.4% Black, 3.3% Asian, and 14% identifying as other ethnicities. At 120 days, mortality was 1% (n=41), ICU admission 5% (n=169), and IMV 2% (n=70). Continuous DLCO was associated with a lower risk of mortality (HR: 0.75; p=0.03), ICU admission (OR: 0.83; p=0.01), and IMV (OR: 0.80; p=0.02). GLI-Global's FEV1 z-scores were also significant for mortality (HR: 0.70; p=0.01), ICU admission (OR: 0.74; p<0.0001), and IMV (OR: 0.70; p=0.0003). Categorical analyses showed significant mortality reduction with normal DLCO (HR: 0.46; p=0.01) and ICU admission reduction with normal FEV1 GLI-2012 (OR: 0.63; p=0.02). Reclassification by race, as shown in Figure 1, indicated that race-specific equations overestimated PFT values in Black patients and underestimated them in Asian patients. Conclusion: Reclassification by GLI reference equations, particularly using continuous z-scores, significantly influences post-HCT outcomes, suggesting that continuous assessment may improve risk stratification. Including race does not improve the model's performance. These findings support integrating updated PFT references and continuous risk models into HCT prognostic tools for enhanced clinical decision-making.