DISCUSSION
In this single center retrospective study of children who underwent HSCT, we found that using Dinakara to correct for Hgb when calculating DLCO resulted in less error at lower Hgb levels compared to Cotes. However, this difference did not affect the ability of either equation to predict survival, nor did pre-transplant DLCO predict post-transplant pulmonary complications. Our results suggest that the method of correction of DLCO for hemoglobin pre-transplant DLCOHgbmay not be the most important factor in predicting post- transplant complications and mortality. Contrary to our hypothesis, the Cotes equation is not superior to Dinakara when predicting morbidity and mortality in the pediatrics HSCT population.
Our results differ from past studies by Coffey et al. and Ginsberg et al. [1, 8] Both studies look at the predictive value of DLCO in the context of two tools used in the adult population that help predict survivability. Coffey et al. demonstrated differences in predictive value of DLCOHgb when using the Cotes equation versus the Dinakara equation in the context of the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), a validated decision making took in adult and pediatric populations. Ginsberg et al demonstrated that DLCO, as part of the Lung Function Score (LFS), was associated with post-transplant survival in a pediatrics population, but they did not investigate differences in how DLCOHgb was calculated. In contrast, our study focused on the predictive value of DLCOHgb alone in a pediatric population and we did not find that it was a good predictor for survival. This could be because we assessed DLCOHgb as an individual predictor and not part of tool that takes other clinical factors into effect. Ginsberg et al. also focused the predictive values of DLCO and other pre-transplant spirometry values for survival; however they did not look specifically at post-transplant complications like infection or post-transplant imaging abnormalities.[8]
Similar to a study by Nitta et al. we found that the differences in corrected DLCO when using Dinakara and Cotes become more pronounced at lower hemoglobin levels, although this did not result in a difference in predicting pulmonary complications between the two methods.[9] The difference in the DLCOHgb when calculated from Dinakara and Cotes highlight the importance of the effect of hemoglobin levels when adjusting DLCO and emphasizes the need to take other patient factors into account when calculating the adjusted DLCO. In this study we also reported other pre-transplant spirometry values and their relationship to post-transplant complications. Similar to findings by Srinivasan et al., we report that lower z-scores for FEV1, FVC, and possibly FEF25-75 are associated with higher risk for post-transplant pulmonary infections and complications.[2]
Our results suggest that using DLCO alone as a predictor of survival is insufficient. DLCO is only one aspect of overall pulmonary function and its clinical interpretation is affected by other factors like anemia and alveolar volume. The causes of death in the HSCT population are often related to respiratory failure in the setting of relapse of disease, GVHD, or infection.[10] The relationship between DLCO and these complications is not well-defined. Furthermore, the studies mentioned above demonstrate that most pediatric patients have normal pre-transplant DLCO values. [2, 6]
There are several limitations to our study. The retrospective and single center study design may have resulted in biased and missing data. The size of our study cohort was similar to other studies, but the relatively small number of patients made it difficult to conduct multivariate modeling to assess the independence of DLCO in the presence of covariates. Other reports have shown that type of transplant, GVHD status, and CMV status affect outcomes, however we were unable to look at these factors due to sample size and incomplete medical records.[11] It is possible that we would have observed significant associations between DLCO and pulmonary outcomes if we had a larger study population and were able to perform multivariable analysis.
In summary, although we found that the Dinakara and Cotes equations differed in their calculation of DLCOHgb at lower Hb levels, their ability to predict mortality and pulmonary complications after HSCT was not different. In the future, prospective study design should focus on comparing risk stratification that incorporates the method used to correct DLCO for Hgb as this will help clarify the role of DLCO in the pediatric pre-stem cell transplant population.