Abstract

Abstract 2917

Background:

The European LeukemiaNet MDS (EUMDS) registry is designed to collect information about the demographics and disease-management of newly diagnosed low-risk and intermediate-1 risk MDS patients. From April 2008 until July 2010, 828 patients have been registered in eleven participating countries through a web-based reporting system.

Objectives:

This report describes the disease-management of the first 800 registered patients, including transfusion-related issues like secondary iron overload and its treatment.

Results:

159 of 800 patients (20%) started MDS specific treatment within three months before registration; this percentage increased to 50% at 18 months of follow-up. Most patients received erythroid-stimulating agents (ESA), like erythropoietin (Table 1). In patients with a clinical indication for ESA, the percentage of transfusion-independency was similar to the transfusion-independent group without indication for ESA at 18 months of follow-up (Table 1). Overall, 27% of the patients received blood transfusions at registration. This percentage remained stable during follow-up, probably due to the therapeutic effect of ESA (Table 1). The number of units transfused, per 6 months, in these patients increased from 5 to 13 units at 18 months of follow-up, with a mean pre-transfusion Hb level of 7.6 g/dL. The serum ferritin levels of the transfusion-dependent patients at registration were available in 159 patients. The serum ferritin level at registration was ≥2000 μg/L in 4% of the patients who received a mean number of 10 units (SD 7). This increased to 28% of the patients who received a mean number of 20 units (SD 11) at 18 months of follow-up. The percentage of patients on iron chelation therapy increased from 1% to 9% during follow-up (Table 1). In these patients the mean serum ferritin levels remained stable: 1913 μg/L (SD 1183) at registration and 1626 μg/L (SD 1232) at 18 months of follow-up. In contrast, transfusion-dependent patients not treated with iron chelation or ESA had increasing ferritin levels, with a mean ferritin of 630 μg/L (SD 597) at registration and 1586 μg/L (SD 1017) at 18 months of follow-up. 37 patients (5%) progressed to high-risk MDS or acute myeloblastic leukemia at a median of 155 days from registration. 62 patients (8%) have died within a median of 269 days from registration, 32 deaths were MDS related. The overall survival was 93% at 18 months of follow-up, with a progression-free survival of 90%. Differences in overall survival between transfusion-independent and transfusion-dependent patients were significant: 97% versus 85%, respectively (p<0.0001; Table 2). In the multivariate analysis transfusion-dependency, ferritin levels and IPSS score predicted survival (Table 2). The IPSS score had a significant prognostic impact on overall survival and progression-free survival in contrast to the WHO classification (Data not shown).

Conclusions:

Despite a high transfusion load the mean serum ferritin levels remained stable during treatment with iron chelation. Transfusion-dependent patients had a worse overall survival and progression-free survival with higher ferritin levels and higher IPSS score as compared to transfusion-independent patients. This report demonstrates the importance of detailed disease-management in low- and intermediate-1 risk MDS patients.

Table 1

Disease-Management over Time

 Registration Follow-up (Months) 
12 18 
Total number of patients 800 539 309 141 
MDS specific treatment 159 (20%) 230 (43%) 146 (47%) 71 (50%) 
Iron chelation 7 (1%) 16 (3%) 25 (8%) 13 (9%) 
ESA1 128 (16%) 184 (34%) 110 (36%) 51 (36%) 
Transfusion-dependent 216 (27%) 158 (29%) 85 (28%) 38 (27%) 
Transfusion-independent with ESA 59 (46%) 72 (39%) 38 (35%) 38 (75%) 
Transfusion-independent no ESA 525 (78%) 261 (75%) 150 (76%) 61 (71%) 
 Registration Follow-up (Months) 
12 18 
Total number of patients 800 539 309 141 
MDS specific treatment 159 (20%) 230 (43%) 146 (47%) 71 (50%) 
Iron chelation 7 (1%) 16 (3%) 25 (8%) 13 (9%) 
ESA1 128 (16%) 184 (34%) 110 (36%) 51 (36%) 
Transfusion-dependent 216 (27%) 158 (29%) 85 (28%) 38 (27%) 
Transfusion-independent with ESA 59 (46%) 72 (39%) 38 (35%) 38 (75%) 
Transfusion-independent no ESA 525 (78%) 261 (75%) 150 (76%) 61 (71%) 
1

ESA=erythroid-stimulating agents

Table 2

Survival at 18 Months of Follow-up

 Total Overall survival Progression-free survival 
  HR (95% CI)1 HR (95% CI)1 
 800   
Transfusions all visits:    
No 497 
Yes 303 5.1 (2.6–10.1) 4.1 (2.4–6.9) 
Ferritin (μg/L):    
1. ≤175 191 
2. >175 & <440 190 3.9 (1.3–1.7) 3.0 (1.3–7.0) 
3. ≥440 190 4.5 (1.5–13.2) 3.2 (1.4–7.4) 
IPSS score:    
389 
0.5 246 1.9 (1.0–3.6) 2.4 (1.4–4.1) 
108 2.2 (1.1–4.7) 3.4 (1.8–6.3) 
 Total Overall survival Progression-free survival 
  HR (95% CI)1 HR (95% CI)1 
 800   
Transfusions all visits:    
No 497 
Yes 303 5.1 (2.6–10.1) 4.1 (2.4–6.9) 
Ferritin (μg/L):    
1. ≤175 191 
2. >175 & <440 190 3.9 (1.3–1.7) 3.0 (1.3–7.0) 
3. ≥440 190 4.5 (1.5–13.2) 3.2 (1.4–7.4) 
IPSS score:    
389 
0.5 246 1.9 (1.0–3.6) 2.4 (1.4–4.1) 
108 2.2 (1.1–4.7) 3.4 (1.8–6.3) 
1

Hazard Ratio (HR) (95% Confidence Intervals (CI)), adjusted for age, International \Prognostic Scoring System score (IPSS) and WHO 2001 classification

Disclosures:

Fenaux:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Cephalon: Honoraria, Research Funding. Bowen:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AMGEN: Honoraria; Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding.

Author notes

*

Asterisk with author names denotes non-ASH members.