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.