Impact of preexisting autoimmune disease on myelodysplastic syndromes outcomes: a population analysis

Abstract

Preexisting autoimmune disease affects 10-30% of patients with myelodysplastic syndromes (MDS). Studies comparing outcomes in MDS patients with and without autoimmune disease show discordant results. Using Surveillance, Epidemiology, and End Results (SEER)-Medicare, we conducted a population analysis to define the impact of autoimmunity on MDS outcomes. Cases were ascertained between 2007 - 2017 and claim algorithms employed to identify autoimmune disease, demographic characteristics, comorbidity scores, MDS histology, transfusion burden, treatment with hypomethylating agents and hematopoietic stem cell transplant. Cox regression models estimated the impact on survival and competing-risk regression models defined the effect on leukemic transformation. We analyzed 15,277 MDS patients, including 2,442 (16%) with preexisting autoimmune disease. The epidemiologic profile was distinctive in cases with preexisting autoimmunity, who were younger, predominantly female and had higher transfusion burden without difference in MDS histologic distribution. Autoimmune disease was associated with 11% decreased risk of death (hazard ratio [HR] 0.89, 95% confidence interval [CI], 0.85 - 0.94, p<0.001). The effect on risk of leukemic transformation differed based on MDS histology. In low-risk MDS histologies, autoimmunity was associated with a 1.9-fold increased risk of leukemia (HR 1.87, 95%CI, 1.17 - 2.99, p=0.008), while no significant effect was seen in other groups. These results suggest that autoimmune disease affects survival in MDS and is associated with decreased mortality. The survival effect was evident in low risk histologies despite higher risk of progression to leukemia. This could represent inflammation-driven hematopoiesis simultaneously favoring less aggressive phenotypes and clonal expansion, which warrants further investigation.

Effects of Autoimmune Disorders on Myelodysplastic Syndrome Outcomes: A Systematic Review

“…For instance, a retrospective study of 1408 MDS patients reported that patients with MDS with ADs achieved significantly better OS than those without ADs after adjusting for covariates such as age and R-IPSS (Revised International Prognostic Scoring System) classification [20]. This finding compares favorably with another retrospective study of 15,227 patients, which reported that the risk of death decreased by 11% in MDS patients with ADs after controlling for covariates such as age, sex, rural residence, immunosuppressive therapy, higher MDS histologic risk, and transfusion dependence [17]. Although the exact reason for this positive association between ADs and survival remains unknown, it might be attributed to the fact that ADs have a neutral or protective role in the later stages of MDS when genetic mutations and clonal evolution are the underlying drivers of the disease.…”

“…Two of these studies showed that MDS patients with ADs had inferior OS compared to those without ADs [18,21]. In contrast, the other two studies reported that ADs were associated with a considerable decrease in mortality risk [17,20]. Moreover, another study reported that OS was better when ADs were diagnosed simultaneously with MDS or after the MDS diagnosis (HR: 0.1; p = 0.008 and HR: 0.024; p = 0.009) [19].…”

The causal effect of autoimmune diseases on myelodysplastic syndrome:a Mendelian randomization study

“…A Spanish study found shorter survival in this subset of patients with MDS combined with autoimmune disease, especially in low-risk MDS patients [10] . This can be explained by the fact that patients with MDS combined with autoimmune diseases have more severe immune dysregulation, which leads to more severe bone marrow failure and disease progression [28] .Conversely, it has been shown that MDS patients combined with autoimmune disease appears to have a better survival bene t. Recently,a US study retrospectively analyzed 15,277 patients with MDS from the SEER Medicare database, of whom 2,442 (16%) had pre-existing autoimmune disease, which reduced the risk of death by 11%.In low-risk MDS, the presence of pre-existing autoimmune disease was associated with an increased risk of leukemic transformation [29] . Another case-control study showed that this group of patients with MDS combined with autoimmune disease had better OS and lower leukemic transformation rates [4] .…”