Abstract
Immune derangements and altered T cell hemostasis play an important role in the pathogenesis of Myelodysplastic syndromes (MDS) contributing to the increased clone susceptibility to accelerated apoptosis. In addition, escape of immune surveillance may be a mechanism of MDS disease progression. The association between MDS and autoimmune diseases (AID) is well described. Small case series reported distinct clinical features and outcome for MDS patients with AID. We report here the largest cohort examining the prevalence of AID among MDS patients, compare characteristics and outcome of MDS patients with and without AID.
We identified all confirmed MDS cases through the Moffitt Cancer Center (MCC) MDS database and King's College Hospital (KCH). Therapy related MDS (t-MDS) cases were excluded. All charts were reviewed for documented past or active AID and its treatment. Patients were divided into 2 groups, those with de novo MDS associated with AID (AIDA-MDS) and those with no documented AID (non AIDA-MDS). Baseline characteristics were compared between the two groups. Chi square test was used for comparison of categorical variables and t-test for continuous variables. Kaplan-Meier estimates were used for overall survival (OS).
At time of this analysis 1408 pts were included, 1044 cases from MCC and 364 at KCH. We identified 391 MDS patients with AID (28%). The median duration of follow up was 74 months (mo) (95% CI 69-78)
Hypothyroidism was the most common AID identified, accounting for 44% (n=171) of cases with AID (12% among all MDS cases in this analysis). Other AID with ≥5% prevalence included ITP 12% (n=46), rheumatoid arthritis 10% (n= 41), gout 9% (n=36), and psoriasis 7% (n=28). To confirm the observed rate of hypothyroidism among our cohort, we explored the rate among MDS pts in the SEER registry where 45% of those registered as MDS had one or more hypothyroid claims (ICD code 244.9) among Medicare beneficiaries (2000-2005). (The prevalence of subclinical hypothyroidism is about 5% of women and in 3% of men with higher prevalence in elderly general population)
Baseline characteristics comparing AIDA-MDS (n=391) and non-AIDA-MDS (n=1017) (summarized in Table-1) were similar except AID were more common in females, RA or RCMDWHO subtype and pts were less RBC transfusion dependent.
Baseline characteristics
| . | . | AIDA-MDS n=391 . | Non AIDA MDS n= 1017 . | P value . |
|---|---|---|---|---|
| Age | > 60 | 293 (75%) | 739 (73%) | 0.4 |
| Gender | Female | 172 (44%) | 305 (30%) | <0.005 |
| WHO | RA | 53 (14%) | 95 (9%) | 0.02 |
| RCMD | 131 (34%) | 299 (29%) | ||
| RARS | 32 (8%) | 90 (9%) | ||
| Del 5q | 12 (3%) | 45 (4%) | ||
| RAEB I | 60(15%) | 193 (19%) | ||
| RAEB II | 56 (14%) | 169 (17%) | ||
| AML | 8 (2%) | 36 (4%) | ||
| CMML | 8 (2%) | 24 (2%) | ||
| MDS U | 13 (3%) | 10 (1%) | ||
| MDS/MPN -U | 18 (5%) | 50 (5%) | ||
| unknown | 0 | 6 (1%) | ||
| IPSS | Low | 85 (23%) | 183 (20%) | 0.25 |
| Int-1 | 186 (50%) | 464 (50%) | ||
| Int-2 | 83 (22%) | 204(22%) | ||
| High | 22 (5%) | 82 (8%) | ||
| R-IPSS | Very low | 68 (19%) | 128 (14%) | 0.1 |
| Low | 127 (35%) | 306(34%) | ||
| Intermediate | 77 (21%) | 188 (21%) | ||
| High | 51 (14%) | 142 (16%) | ||
| Very High | 41 (11%) | 135 (15%) | ||
| Hypocellular marrow | MCC only/Yes | 31 (10%) | 70 (10%) | 0.5 |
| Marrow Fibrosis | MCC only/Grade 2-3 | 40 (13%) | 95 (13%) | 0.7 |
| PNH clone | detected | 6 (2%) | 14 (1%) | 0.8 |
| LGL clone | MCC only / >500 | 24 (8%) | 41 (6%) | 0.053 |
| T cell clonality | MCC only / + Beta or gamma | 28/71 (39%) | 55/112 (40%) | 0.5 |
| Karytotype | Favorable | 260 (66%) | 640 (65%) | 0.4 |
| Intermediate | 67 (17%) | 152 (15%) | ||
| Poor | 59 (15%) | 183 (19%) | ||
| missing | 5 (1%) | 15 (2%) | ||
| Trisomy 8 | Yes | 44 (12%) | 89 (9%) | 0.3 |
| RBC transfusion | Dependence | 256 (66%) | 729 (72%) | 0.016 |
| HMA (MCC) | Azacitidine | 168 (54%) | 344 (47%) | 0.8 |
| Decitabine | 38 (12%) | 119 (16%) | 0.1 |
| . | . | AIDA-MDS n=391 . | Non AIDA MDS n= 1017 . | P value . |
|---|---|---|---|---|
| Age | > 60 | 293 (75%) | 739 (73%) | 0.4 |
| Gender | Female | 172 (44%) | 305 (30%) | <0.005 |
| WHO | RA | 53 (14%) | 95 (9%) | 0.02 |
| RCMD | 131 (34%) | 299 (29%) | ||
| RARS | 32 (8%) | 90 (9%) | ||
| Del 5q | 12 (3%) | 45 (4%) | ||
| RAEB I | 60(15%) | 193 (19%) | ||
| RAEB II | 56 (14%) | 169 (17%) | ||
| AML | 8 (2%) | 36 (4%) | ||
| CMML | 8 (2%) | 24 (2%) | ||
| MDS U | 13 (3%) | 10 (1%) | ||
| MDS/MPN -U | 18 (5%) | 50 (5%) | ||
| unknown | 0 | 6 (1%) | ||
| IPSS | Low | 85 (23%) | 183 (20%) | 0.25 |
| Int-1 | 186 (50%) | 464 (50%) | ||
| Int-2 | 83 (22%) | 204(22%) | ||
| High | 22 (5%) | 82 (8%) | ||
| R-IPSS | Very low | 68 (19%) | 128 (14%) | 0.1 |
| Low | 127 (35%) | 306(34%) | ||
| Intermediate | 77 (21%) | 188 (21%) | ||
| High | 51 (14%) | 142 (16%) | ||
| Very High | 41 (11%) | 135 (15%) | ||
| Hypocellular marrow | MCC only/Yes | 31 (10%) | 70 (10%) | 0.5 |
| Marrow Fibrosis | MCC only/Grade 2-3 | 40 (13%) | 95 (13%) | 0.7 |
| PNH clone | detected | 6 (2%) | 14 (1%) | 0.8 |
| LGL clone | MCC only / >500 | 24 (8%) | 41 (6%) | 0.053 |
| T cell clonality | MCC only / + Beta or gamma | 28/71 (39%) | 55/112 (40%) | 0.5 |
| Karytotype | Favorable | 260 (66%) | 640 (65%) | 0.4 |
| Intermediate | 67 (17%) | 152 (15%) | ||
| Poor | 59 (15%) | 183 (19%) | ||
| missing | 5 (1%) | 15 (2%) | ||
| Trisomy 8 | Yes | 44 (12%) | 89 (9%) | 0.3 |
| RBC transfusion | Dependence | 256 (66%) | 729 (72%) | 0.016 |
| HMA (MCC) | Azacitidine | 168 (54%) | 344 (47%) | 0.8 |
| Decitabine | 38 (12%) | 119 (16%) | 0.1 |
Median OS was 60 mo (95% CI 50-70) for AIDA-MDS compared to 45 mo (95% 40-49) for those with no AIDA-MDS (log rank test, p = 0.006). By multivariate analysis adjusting for revised IPSS and age >60, AID was a statistically significant independent factor for OS (HR 0.78 (95% CI 0.66-0.92) (p=0.004). The rate of AML transformation was 23% (n=89) among AIDA-MDS compared to 30% (n=301) in non AIDA-MDS (p=0.006). There were no observed differences in response to treatment including azacitidine or Lenalidomide among evaluable patients for response.
AID are commonly associated with MDS, accounting for 28% of patients in our large cohort. Hypothyroidism was the most prevalent AID (12%) with similar high observation among Medicare MDS beneficiaries. AID was significantly more common in women, and associated with more RA/RCMD WHO subtypes with significantly reduced risk of AML transformation and death.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
