Abstract

Abstract 3830

Background:

The EUMDS registry was established to obtain an overview in the real world MDS demographics, diagnostics and disease-management. From April 2008 until December 2010, 1000 newly diagnosed patients with IPSS low and int-1 risk MDS were included in 14 countries and 118 participating centers. The major clinical problems in MDS are the consequences of cytopenias and disease-progression. Therefore, the most important treatment goals are improvement of cytopenias and prevention of leukemia.

Objectives:

To describe the causes of early mortality and to analyze the outcome of the first 1000 patients in the registry with and without disease-progression at 24 months follow-up.

Results:

The median age of the population was 74 years (range 18–95), 60% were male. The most frequent co-morbidities were hypertension (46%), diabetes mellitus (18%), arrhythmias (12%), and thyroid diseases (12%). The WHO subgroups are RCMD (39%), RA (19%), RARS (17%), RAEB-1 (13%), RCMD-RS (7%), MDS-U (3%), and del5q (2%). IPSS score (n=935) was 0 in 48%, 0.5 in 31% and 1 in 14% of the patients. WPSS score (n=924) was Very Low in 32%, Low in 38%, Intermediate in 19% and High in 4% of the patients (Table1). 184 of 1000 patients (18%) had started MDS specific treatment within 3 months after diagnosis: this increased to 43% at 24 months of follow-up. 15% of the patients (in 12 of the 14 countries) started ESA treatment at registration and this increased to 31% at 24 months, combined with G-CSF in 7%. At registration, 29% of the patients had received at least one RBC transfusion with a mean pre-transfusion Hb level of 8 g/dL. The percentage of transfusion-dependent (TD) patients remained stable during follow-up with 31%, 29%, 26% and 29% at 6, 12, 18, 24 months of follow-up, respectively. At 24 months, overall survival (OS) is 83%. Median time from date of inclusion until progression to higher risk MDS or leukemia is 293 days. Most patients (123) have died without disease-progression (DP) versus 45 patients who have died after DP at 24 months (Table1). DP has been defined as an increase in bone marrow blasts to a higher WHO category. The main causes of death in patients without DP were infections (21%) and cardiovascular events (11%). The mortality rate in transfusion-independent (TI) and TD patients without DP was 5% and 24%, respectively. In TI and TD patients with DP, the mortality rate was 32% and 66%, respectively (Table1; Graph 1). To define the prognostic relevance of serum ferritin (SF) and TD, the SF levels divided in two groups (1. <1000 μg/L, 2. ≥1000 μg/L) were compared in TI and TD patients and stratified by disease-progression. The mortality rate according to SF at registration in TI patients without DP was 9% and 13%, respectively (HR 1.61, 95%CI 0.49–5.37). The mortality rate according to SF at registration in TD patients without DP was 21% and 56%, respectively (HR 4.79, 95%CI 2.56–8.96) (Table 1).

Conclusions:

The great majority of deceased lower risk MDS patients have died before they have developed clinical signs of disease-progression. Transfusion-dependent patients without disease-progression have a four times higher mortality rate than transfusion-independent patients. This indicates that the pathophysiology of cytopenias and related complications are a major point of interest in early mortality, especially in patients without disease-progression.

Table 1:

Overall Survival at 2 years, stratified by disease-progression

 Total No Progression Progression 
 Died Overall survival HR (95% CI)1 Died Overall survival HR (95% CI)1 
N 1000 123  45  
IPSS score:      
484 52 
0.5 314 42 1.44 (0.96–2.16) 17 0.55 (0.22–1.34) 
137 22 1.88 (1.14–3.09) 14 1.52 (0.59–3.89) 
WPSS score:      
Very Low 316 29 
Low 378 53 1.5 (0.95–2.38) 17 0.48 (0.15–1.56) 
Intermediate 191 22 1.41 (0.81-2.46) 13 1.1 (0.33-3.68) 
High 39 12 4.2 (2.14–8.26) 1.84 (0.45–7.55) 
Transfusions2:      
No 540 28 
Yes 460 95 4.12 (2.65–6.4) 38 1.51 (0.64–3.56) 
Transfusion-dependent:      
Ferritin at registration      
1. <1000 μg/L 176 33 13 
2. ≥1000 μg/L 43 18 4.79 (2.56–8.96) 0.76 (0.26–2.21) 
 Total No Progression Progression 
 Died Overall survival HR (95% CI)1 Died Overall survival HR (95% CI)1 
N 1000 123  45  
IPSS score:      
484 52 
0.5 314 42 1.44 (0.96–2.16) 17 0.55 (0.22–1.34) 
137 22 1.88 (1.14–3.09) 14 1.52 (0.59–3.89) 
WPSS score:      
Very Low 316 29 
Low 378 53 1.5 (0.95–2.38) 17 0.48 (0.15–1.56) 
Intermediate 191 22 1.41 (0.81-2.46) 13 1.1 (0.33-3.68) 
High 39 12 4.2 (2.14–8.26) 1.84 (0.45–7.55) 
Transfusions2:      
No 540 28 
Yes 460 95 4.12 (2.65–6.4) 38 1.51 (0.64–3.56) 
Transfusion-dependent:      
Ferritin at registration      
1. <1000 μg/L 176 33 13 
2. ≥1000 μg/L 43 18 4.79 (2.56–8.96) 0.76 (0.26–2.21) 
1

Hazard Ratio (HR) (95% Confidence Intervals (CI)): IPSS, WPSS score adjusted for age, sex, country;

Transfusions, TD and Ferritin adjusted for age, sex, country, WHO category, cytogenetics, cytopenias, % blasts

2

At least one red blood cell transfusion recorded at registration or follow-up

Graph 1.

Overall Survival stratified by disease-progression and RBC transfusions

Graph 1.

Overall Survival stratified by disease-progression and RBC transfusions

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.