Comorbidities and Overall Survival In Myelodysplastic Syndromes (MDS): Development of a Prognostic Model Incorporating IPSS and Age with ACE-27 Comorbidity Index
Authors: Naqvi Kiran , Suarez-Almazor Maria E , Sardesai Sagar , Oh Jeong , Vigil Carlos , Pierce Sherry , Lei Xiudong , Shan Jianqin , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: October 2019

Abstract
Abstract 605

Background:
Cancer patients often experience comorbidities that may affect their therapeutic options, prognosis, and outcome. Limited studies have evaluated the characteristics and impact of comorbidities in MDS. The aim of this study was to determine the effect of comorbidities on the survival of patients with MDS.

Methods:
We reviewed the medical records of 600 consecutive MDS patients who presented to MD Anderson Cancer Center from 01–2002 to 06–2004. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients, was used to assess the severity of comorbid conditions. Data on demographic characteristics, International Prognostic Scoring System (IPSS), stem cell transplant (SCT) and outcomes (leukemic transformation and survival) was collected. Kaplan-Meier methods and log-rank tests were used to assess survival. Multivariate analysis was performed using the Cox Proportional Hazards Model. A prognostic model incorporating baseline comorbidities with age and IPSS was developed to predict survival. A score point for each significant factor (age, IPSS and ACE-27 comorbidity score) was obtained by dividing respective coefficients from the multivariate model by 0.3 and rounding to the nearest integer.

Results:
Of the 600 patients included in this study, 400 (65.7%) were male, and 518 (87.1%) were white; median age at presentation was 66.6 years (range 17.3 – 93.5); median duration of follow-up was 14.8 months (range 0–88). The ACE-27 comorbidity scores were as follows: none, 137 patients (28.8%); mild, 254 (42.3%); moderate, 127 (21.2%); and severe, 82 (13.7%). Four hundred and fifty six (76.0%) patients died, 123 (20.5%) suffered leukemic transformation and 51 (8.5%) patients underwent SCT. Overall median survival using the Kaplan-Meier method was 18.6 months. Median survival according to ACE-27 scores was: 31.8, 16.8, 15.2 and 9.7 months for none, mild, moderate and severe comorbidity scores respectively (p < 0.0001). The adjusted hazards ratios from the multivariate Cox Proportional Hazards Model were 1.3, 1.6 and 2.3 for mild, moderate and severe comorbidity scores when adjusted for age and IPSS (p < 0.0001). A final prognostic model incorporating comorbidity score with age and IPSS was developed. A risk score was derived based on the regression coefficients from the final multivariate model. The score points assigned were: Age > 65 years=2; IPSS of Intermediate-2= 2 and High= 3; ACE-27 score of mild or moderate= 1 and Severe= 3. Based upon their risk scores, patients were categorized into 3 groups: low (0 - 1), intermediate (2 - 4) and high (5 – 8). Almost 50% of the patients in our study were noted to be in the intermediate category with a median survival of 23 months. The model confirmed a better survival in patients in low risk group of 43 months versus 9 months in the high risk group (p < 0.001).

Conclusion:
Comorbidities had a significant impact on the survival of patients with myelodysplastic syndrome. Patients with higher ACE-27 comorbidity scores had a shorter survival than those with no comorbidity, independent of their age and the IPSS risk group. A comprehensive assessment of comorbidity is therefore needed to determine the prognosis in patients with MDS. Our newly developed prognostic model helps predict survival in such patients based on their comorbidities.

Disclosures:
No relevant conflicts of interest to declare.