Comorbidity as Prognostic Variable in MDS: Comparative Evaluation of the HCT-CI and CCI in a Core Data Set of 582 Patients of the Austrian MDS Platform.
Authors: Sperr Wolfgang R , Wimazal Friedrich , Kundi Michael , Baumgartner Christian , Noesslinger Thomas , Makrai Anabel , Stauder Reinhard , Krieger Otto , Pfeilstocker Michael , Valent Peter 
Published: April 2020

Abstract
Myelodysplastic syndromes (MDS) are a group of clonal myeloid neoplasms characterized by ineffective erythropoiesis, peripheral cytopenia(s), and an increased risk to transform to secondary acute myeloid leukemia (AML). The prognosis in MDS is variable and depends on the variant of disease, other disease-related features, and patient-related parameters. In the present study, the influence of comorbidity on survival and AML evolution was analyzed retrospectively in 582 patients (270 females and 312 males, f/m ratio: 1:1.2) with de novo MDS (observation period: 1985–2007). The median age was 71 years (range 18–96 years). Of the 582 patients, 275 died so far. The median survival (OS) of all patients was 3.12 years, and the median event-free survival (EFS) was 2.3 years. The median AML-free survival (AFS) was not reached. All in all, 127 patients (22%) developed secondary AML after a median time of 9.7 months (range 0.3–116.6 months). Two different scoring systems for comorbidity, the hematopoietic stem cell transplantation comorbidity index (HCT-CI) and the Charlson comorbidity index (CCI) were applied. As assessed by log rank test, the overall survival (OS) was found to differ among patients in the three different HCT-CI risk groups (p&lt;0.05) and among patients in the four different CCI risk groups. By univariate analysis, the HCT-CI was found to be of prognostic value for OS and EFS in patients meeting WHO- or FAB criteria (p&lt;0.05). The CCI was also found to be of prognostic value for OS in patients diagnosed according to either WHO or FAB criteria (p&lt;0.05). With regard to EFS, the CCI was a prognostically significant variable only for patients meeting WHO criteria (p&lt;0.05), but not in patients diagnosed according to FAB criteria (p&gt;0.05). Calculating AML-free survival (AFS), neither the CCI nor the HCT-CI were of prognostic significance (p&gt;0.05). To evaluate whether comorbity is an independent prognostic parameter in patients with MDS, multivariate analyses were performed. These analyses included the HCT-CT or the CCI together with IPSS, LDH, and the patients’ age. In these analyses, chronic comorbid conditions were found to be independent prognostic risk factors concerning OS and EFS, but not concerning AFS. Specifically, the HCT-CI was an independent prognostic parameter regarding OS (p&lt;0.05) and EFS (p&lt;0.05) for patients diagnosed according to WHO- or FAB-criteria. In contrast, the CCI was of prognostic significance regarding OS for patients meeting WHO- or FAB-criteria, whereas the CCI was not found to be an independent prognostic factor regarding EFS (p&gt;0.05). Regardless of the score applied (HCT-CI or CCI), the highest predictive value of comorbidity was observed in IPSS low risk patients (p&lt;0.05) concerning OS. Of the other variables included in our multivariate analysis, the IPSS was an independent prognostic parameter for OS, EFS, and AFS. Interestingly, age was an independent prognostic variable for OS and EFS, but not concerning AFS, similar to the impact of comorbidity, whereas LDH was an independent predictive factor concerning EFS and AFS. Together, our data show that comorbidity is an independent risk factor for survival in patients with MDS. Therefore, comorbidity should be considered as an important co-variable in the risk assessment in MDS and in the overall treatment plan in these patients.