The V50/V25 Ratio, a Marker of Small Airway Disease, Is Highly Predictive of Survival after Allogeneic Hematopoietic Cell Transplantation

Some studies that evaluated the predictive value of lung function prior to allogeneic hematopoietic stem cell transplant (allo-SCT) showed a statistically significant relationship between pulmonary function test (PFT) parameters and outcome. However, patients infrequently display significant abnormalities in lung function before allo-SCT, specifically forced expiratory volume in one second (%FEV1.0) and vital capacity (%VC). In addition, the underlying mechanism for the abnormalities in PFT parameters present before allo-SCT remains elusive.

V50/V25 ratio is known to be a sensitive marker of small airway obstruction and an abnormal V50/V25 ratio often becomes detectable even in patients in whom %FEV 1.0 and/or %VC are normal. To our knowledge, nobody has reported the effect of the V50/V25 ratio on outcome in patients undergoing allo-SCT.

We here comprehensively evaluate the effect of PFT parameters determined before allo-SCT on survival and outcomes. We also address the causes of deterioration in PFT indicators. We retrospectively studied 159 evaluable patients who received allo-SCT at our institute between June in 2004 and December in 2012, and who had available PFT data acquired before allo-SCT (median age 46). The median follow-up duration for survivors was 875 days. We evaluated PFT indicators including %VC, %FEV1.0, MMF, %RV, RV/TLC, FVC, FEV1.0/FVC, DLco/VA, V25 and V50/V25 ratio. Analysis using a univariate Cox proportional hazard model showed that %VC, %FEV1.0, DLco/VA, RV/TLC, and V50/V25 ratio (all P< 0.05) were significantly compromised in patients who died. On multivariate analysis, %VC, DLco/VA and V50/V25 retained statistical significance (all P-<0.01). Notably, among these significant parameters, V50/V25 was found to be the most sensitive and powerful indicator of survival after allo-SCT (HR: 2.15 per 1-SD-magnitude, 95% CI: 1.53-3.03, P<0.0001). In addition, 56% of all patients had an abnormal V50/V25 (>3.0) pre allo-SCT, whereas in just 12% and 11% respectively were the %FEV1.0 (< 80%) and %VC (< 80%) abnormal. Moreover, the V50/V25 determined before allo-SCT was significantly correlated with age (P <.001) and smoking history (P <.05) but not type of disease, disease status, performance status, intervals between diagnosis and transplantation.

Next, we established a scoring system for lung function by applying three independently significant parameters. Importantly, the three indicators for which statistical significance was detected have distinct physiological implications. V50/V25 is a marker of obstruction, %VC, a measure of lung capacity, and diffusing capacity for carbon monoxide/alveolar volume (DLco/VA), a measure of diffusing capacity. We assigned a separate score (%VC; < 80% = 1 and > 80% = 0, DLco/VA; < 80% = 1 and > 80% = 0, V50/V25; >3.25=1 and < 3.25 = 0) and stratified all patients into the four group by total score. The scoring system consisting of %VC, DLco/VA and V50/V25 represented a significant discriminating variable for prediction of survival after allo-SCT (Figure 1).

In the current study, our data demonstrate the predictive value of a sensitive small-airway disease indicator, V50/V25, for survival. Although we cannot exclude the presence of other potential factors affecting V50/V25 in hematological patients, our results demonstrate that V50/V25 might be significantly compromised by age, and/or smoking before allo-SCT. In addition a scoring system that incorporates V50/V25 instead of %FEV1.0 may be a potentially useful clinical tool for prediction of survival after allo-SCT.

Figure 1

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Figure 1

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