Early Mortality in 1000 Newly Diagnosed MDS Patients with Low- and Intermediate-1 Risk MDS in the European Leukemianet MDS (EUMDS) Registry
Authors: de Swart Louise , Smith Alex , Fenaux Pierre , Sanz Guillermo , Hellstrom-Lindberg Eva , Symeonidis Argyris , Cermak Jaroslav , Germing Ulrich , Stauder Reinhard , Georgescu Otilia , MacKenzie Marius , Malcovati Luca , Holm Mette Skov , Madry Krzysztof , Park Sophie , Beyne-Rauzy Odile , Droste Jackie , Bowen David , de Witte Theo 
Published: October 2019

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.

Disclosures:

No relevant conflicts of interest to declare.