Correlation Between serum ferritin Level at diagnosis and Survival In Lower Risk, Non-Transfusion Dependent, MDS Patients.A Report by the Groupe Francophone Des Myelodysplasies (GFM)

Increased serum ferritin (SF) level has been associated with worse overall survival (OS) in lower risk MDS, presumably though iron overload in vital organs including the heart and liver (Cazzola, NEJM 2005, Malcovati, JCO 2005, Garcia-Manero G et al. Leukemia 2008). However, those high levels are generally associated with RBC transfusion requirement (Malcovati, JCO 2007, Sanz, Blood (ASH 2008 : Abstract 640). High SF level has also been reported in non transfused lower risk MDS, and attributed mainly to ineffective erythropoiesis, but its prognostic value in this context is unclear. We evaluated the prognostic value of SF level at diagnosis in lower risk non transfusion dependent (TD) MDS patients included in the GFM registry of MDS.

We selected in the GFM Registry (1900 pts included between mid 2003 and 2010), 485 newly diagnosed IPSS low and int 1 (lower) risk MDS patients (pts), not transfused during the first 6 months of follow-up, who had a baseline SF level (normal values 20–300 ng/ml), and no other cause of increased SF, including infection and liver disease (due in particular to alcohol abuse). Pts with SF < 20ng/mL were excluded. The prognostic value of SF for AML progression and OS was analyzed.

Median age of the 485 pts was 77 years (range 29–103), with 53.8% males. WHO classification was RA 21.5%, RCMD 23.5%, RARS 23%, RCMD-RS 0.5%, RAEB-1 22% and 5q- syndrome 5%. Karyotype according to IPSS was fav (61%), int (10%), unfav (2%), not available (17%). IPSS was 0 (44%), 0.5 (31%), 1 (8%), ND (17%). The median level of SF was 276ng/ml (range 20–5558) with 225 (46%), 145 (30%) and 47(10%) pts having SF>300ng/ml, >500ng/ml and >1000ng/ml respectively (resp.). In univariate analysis, male gender (P=0.0005), Hb level<10g/dl (P=0.0013), MCV >100μm3 (P=0.02), erythroblasts >30% in bone marrow (P=0.008), serum (s) EPO level>100IU/l (P=0.04), RARS (P<0.0001) were significantly associated with increased SF level (ie. >300ng/ml) while karyotype, IPSS, % marrow blasts, reticulocytes, platelets showed no correlation. In multivariate analysis, sEPO level>100IU/l and RARS were significantly associated with higher SF level.

As the SF threshold of 1000ng/mL is often proposed to start chelation therapy, prognostic analyses were also made for that level. Hb level <10g/dl, and sEPO level>100 were associated with SF >1000 ng/ml in univariate analysis, while only Hb level<10g/dl still showed a correlation in multivariate analysis.

5-year OS was 77% and 85% in pts with baseline SF<300 and >300ng/ml resp. (p=0.7) and 81% vs 92% for SF<1000 and >1000ng/ml, resp. (p=0.11) and 5-year cumulative incidence of AML transformation was 2.2% and 3.3% for pts with SF<300ng/ml and >300ng/ml resp (P=0.69), and 3% and 0% for pts with SF<1000ng/ml and >1000ng/ml resp (P=0.86).

Increased baseline SF level in non transfusion-dependent lower risk MDS is correlated with a few baseline characteristics including more severe anemia, a diagnosis of RARS and higher baseline serum EPO level, but is not significantly correlated with outcome.

Fenaux:CELGENE: Honoraria, Research Funding; JANSSEN CILAG: Honoraria, Research Funding; AMGEN: Honoraria, Research Funding; ROCHE: Honoraria, Research Funding; GSK: Honoraria, Research Funding; NOVARTIS: Honoraria, Research Funding; MERCK: Honoraria, Research Funding; CEPHALON: Honoraria, Research Funding.