Positive Impact of Iron Chelation Therapy (CT) on Survival in Regularly Transfused MDS Patients. A Prospective Analysis by the GFM.
Authors: Rose Christian , Brechignac Sabine , Vassilief Dominique , Beyne-Rauzy Odile , Stamatoullas A. , Larbaa Dalila , Guerci Agnes , Roy L. , Dumazert Lydia , Mahe Beatrice , Cheze S. , Quesnel Bruno , Bordessoule Dominique , Dreyfus Francois , Fenaux Pierre 
Published: April 2020

Abstract
Background: RBC transfusions are required in most MDS, leading to iron overload which probably contributes to shortened survival (Malcovati, JCO, 2005). Consensus for indications of iron chelation therapy (CT) in MDS patients are recent (Gattermann Hemato/Oncol Clin2005; 19:supp1). A positive impact on survival of CT, clearly demonstrated in thalassemia, has not yet been prospectively reported in large MDS cohorts.
Methods: We performed in 2005 a survey on hematological data, RBC transfusion requirement and CT in 170 MDS referred for RBC transfusion during a month period (May 15–June 15, 2005) to 18 French GFM centers (Rose, ASH 2006, abstr:2661). Survival of this prospective cohort was reanalyzed at the reference date of May 15, 2007.
Results: 5 pts were lost to follow up. Median age of the remaining 165 pts was 77 (range 14–95).M/F 1.4. WHO: 13 pure RA (10%), 30 pure RARS (23%), 6 RCMD (5%),5 RCMD-RS (4%), 28 RAEB I (21%), 10 RAEB II (8%),11 5q- Sd (7%), 8 CMML (6%); 21 MDS unclass (16%). Karyotype: fav (12%), int (36%), unfav (22%), failure or ND (30%) IPSS: low 27%, Int1 32%, Int2 10%, high 2%, unavailable 29%. 76 pts (46%) received CT for at least 6 months, including 65 before May 2005, and 11 since May 2005. Median interval from diagnosis to onset of CT was 30 months (range 0–192). CT included: DFO continuous s/c (8h) (40mg/kg/d, 3 – 5d/w) n= 41, deferiprone alone (30 to 75 mg/kg/d) n= 5, Deferiprone + DFO s/c n= 5, deferasirox (20 to 30 mg/kg/d) n= 6 (Defined as “standard” chelation) and DFO s/c bolus (2 to 3g/week) n = 12 or DFO IV (50 to 100mg/kg/d once after each RBC transfusion) n= 7 (defined as “low” chelation). Median duration of CT was 35 months (6–138+). Median serum ferritin (SF) level was 569ng/ml (range 9–2500), 1436ng/ml (range 436–6572) and 1498ng/ml (range 272–7502) at diagnosis, onset of CT and last evaluation, respectively (resp). By comparison to non chelated pts, chelated pts had significantly higher number of RBC units transfused (mean 104 vs 57) (p&lt;0.001), lower age (mean 70 vs 76) (p= 0.006) no difference in WHO classification (p=0.274) but differences in IPSS: IPSS 0; 0–1,&gt;1 in 27%, 53%, 20% of non chelated versus 49%,36%,15% of chelated pts with available IPSS, resp (p=0.044). Median overall survival from diagnosis (OS, Kaplan-Meier analysis) was 115 and 51 months in chelated and non chelated pts,resp (p&lt; 0.0001). After adjustment on other prognostic parameters (sex,age, IPSS, transfusion requirement) the survival difference remained significant. In IPSS 0 pts, median OS was not reached in chelated pts and 69 months in non chelated pts(p=0.002).In IPSS 0–1 pts, median OS was 115 months in chelated pts and 50 months in non chelated pts (p=0.003). Longer interval from diagnosis to onset of CT did not influence OS negatively but median OS was 120 months with “standard” chelation versus 69 months with “low “chelation (p&lt;0.001).
Conclusions: This prospective analysis strongly suggests that chelation therapy (CT) provides survival benefit in heavily transfused, mainly low and int 1, MDS. Confirmatory randomized trials, theoretically required,(CT vs no CT) may be difficult to perform in this situation.