The Impact of Comorbidities on Clinical Outcome of Patients with Myelodysplastic Syndromes: A Real-Life Survey
Authors: Balleari Enrico , Salvetti Chiara , Bacigalupo Andrea , Forni Gianluca , Gobbi Marco , Ghio Riccardo , Scudeletti Marco , Tassara Rodolfo , Berisso Giovanni , Calzamiglia Tullio , Arboscello Eleonora , Beltrami Germana , Bergamaschi Micaela , Cavalleri Maurizio , Del Corso Lisette , Favorini Serena , Filiberti Rosa , Goretti Riccardo , Miglino Maurizio , Mitschoning Laura , Molinari Elisa , Racchi Omar , Clavio Marino 
Published: October 2019

Abstract
Introduction: Myelodysplastic syndromes (MDS) are a highly heterogeneous group of clonal disorders, with very different prognosis in given individuals, overall survival (OS) ranging from more than 10 years (y) for the more indolent conditions to only few months (m) for the forms approaching AML; beside of the well-established disease-related prognostic systems (classical IPSS or its revised form [IPSS-R], the prognostic implication of comorbidities is emerging as a relevant patient-related factor influencing clinical outcome. Aim of our study was to evaluate the clinical impact of comorbidities in a series of MDS patients whatever treated in a “real-life” setting.
Methods: this retrospective cohort study involved the MDS patients consecutively registered between Jan 2011 and Dec 2013 into the Registro Ligure delle Mielodisplasie database, a regional registry established within the framework of the Italian Network of regional MDS registries. Data of 318 patients (pts) with available complete assessment of comorbidities at diagnosis were included into the study. The clinical characteristics and comorbidities were all considered into the analysis. Comorbidities were evaluated according to both hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and MDS-specific comorbidity index (MDS-CI). All survival analyses were made from the date of diagnosis to last follow-up, death, or progression to AML. Unless specified, survival analyses were Cox models using continuous variables accounting for interactions.
Results: Our cohort mainly consisted of older (median age 75y (range 40-98) “lower-risk” MDS pts: according to IPSS stratification, 151 (54.7%) pts were classified as low-risk, 86 (31.2%) as intermediate-1, 32 (11.6%) as intermediate-2 and 7 (2.5%) were in the high-risk group.
One or more comorbidity of any grade of severity was seen in 177 (55.7%) pts at diagnosis. The more common comorbidity was cardiac (26.5%). At least a single comorbidity was present in 61.2% of pts older than 75y and in 50.6% of younger pts (p=0.07). Cardiovascular disorders were more frequent among older (32.9% for >75y vs 15.1% for ≤ 75y, p<0.001), and among males (28.7% vs 17.1% for females, p=0.02). According to HCT-CI risk stratification, 141pts (44.3%) were in the low-risk group, 94 (29.6%) in the intermediate-risk group, and 83 (26.1%) in the high-risk group, while according to MDS-CI, 197 (61.9%) pts had a low-risk score, 99 (31.1%) were intermediate, and 22 (6.9%) were in the high-risk group. MDS-CI score was higher among males (43.8% vs 30.7% for females, p=0.02). It was also higher among subjects >75 y (48% vs. 28.9% for < 75 y (p=0.001). A lower comorbidity score impacted on the clinical choice for active forms of therapy, while pts with an higher burden of comorbidities were preferentially treated with supportive care, even if difference did not reach significance (p=0.07).
Overall survival and risk of non-leukemic death (NLD) were analyzed (median f.u. 26.9 m (range 1-220). HCT-CI did not significantly correlated with OS nor NLD (p= 0.1 and p= 0.07, respectively), while MDS-CI was found to be of prognostic significance both for OS (mean 136.6 (95%CI 116-157) m for the low-risk group, 81.3 (95%CI 61-102) m for the intermediate group and 48.1 (95%CI 30-66) m for the high-risk group, p=0.001) and for NLD (mean 159.6 (95%CI 139-180) m for the low-risk group, 96.5 (95%CI 72-121) m for the intermediate group and 49 (95%CI 31-67) m for the high-risk group (p<0.001). The correlation was significant (p<0.001) in IPSS or IPSS-R “lower-risk” (low and intermediate-1 risk or very-low, low and intermediate groups, respectively) but not in IPSS nor IPSS-R “higher-risk” (intermediate-2 and high or high and very-high groups, respectively) pts. In multivariate analysis, the prognostic impact of MDS-CI remained independent of baseline IPSS (p=0.01) or IPSS-R (p=0.03).
Conclusions: a comprehensive evaluation of comorbidities according to a tailored tool such is MDS-CI helps to predict survival in patients with MDS and should be incorporate to current prognostic scores in order to better define clinical management of these patients.

Disclosures
No relevant conflicts of interest to declare.