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Many patients with primary myelofibrosis (PMF) become red blood cell (RBC) transfusion dependent (TD), risking iron overload (IOL). Iron chelation therapy (ICT) may decrease the risk of haemosiderosis associated organ dysfunction, though its benefit in PMF is undefined. To assess the effect of TD and ICT on survival in PMF, we retrospectively reviewed 41 patients. Clinical data were collected from the database and by chart review. The median age at PMF diagnosis was 64 (range 43-86) years. Median white blood cell (WBC) count at diagnosis was 7.6 (range 1.2-70.9) x 10(9)/L; haemoglobin 104 (62-145) G/L; platelets 300 (38-2088) x 10(9)/L. Lille, Strasser, Mayo and International Prognostic System (IPS) scores were: low risk, n = 15, 8, 11, 3; intermediate, n = 15, 19, 9, 16; high, n = 5, 11, 5, 7; respectively. Primary PMF treatment was: supportive care, n = 23; hydroxyurea, n = 10; immunomodulatory, n = 4; splenectomy, n = 2. Sixteen patients were RBC transfusion independent (TI) and 25 TD; of these 10 received ICT for a median of 18.3 (0.1-117) months. Pre-ICT ferritin levels were a median of 2318 (range 263-8400) and at follow up 1571 (1005-3211 microg/L (p = 0.01). In an analysis of TD patients, factors significant for overall survival (OS) were: WBC count at diagnosis (p = 0.002); monocyte count (p = 0.0001); Mayo score (p = 0.05); IPS (p = 0.02); number of RBC units (NRBCU) transfused (p = 0.02) and ICT (p = 0.003). In a multivariate analysis, significant factors were: NRBCU (p = 0.001) and ICT (p = 0.0001). Five year OS for TI, TD-ICT and TD-NO ICT were: 100, 89 and 34%, respectively (p = 0.003). The hazard ratio (HR) for receiving >20 RBCU was 7.6 (95% Confidence Intervals [CI] 1.2-49.3) and for ICT was 0.15 (0.03-0.77). In conclusion, 61% of PMF patients developed RBC-TD which portended inferior OS; however patients receiving ICT had comparatively improved OS, suggesting a clinical benefit. Prospective studies of IOL and the impact of ICT in PMF are warranted.

Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia (AML). Many MDS patients (pts) require red blood cell (RBC) transfusions, risking iron overload (IOL)-related organ dysfunction. We previously showed in a multivariate analysis of 178 pts, improved survival in 18 pts with low and int-1 IPSS risk MDS and IOL receiving iron chelation therapy (ICT), and now examine the effect of ICT on AML-free survival (LFS). The effect of ICT on cytopenias and RBC transfusion requirements (TR); was also examined. To control for possible bias favoring ICT pts, a subgroup analysis was performed. Each of 18 ICT pts had a non-ICT control pt (CP) selected and these groups are matched for gender; neutrophil count (NC), platelet count (PLTC) and hemoglobin (Hb) at diagnosis (Dx); MDS subtype; no of cytopenias, karyotype; IPSS score; ECOG Performance Status; no of serious infections; initial ferritin level (FL); total RBC units (U) received; primary MDS treatment (Rx); and duration of follow-up (FU; all p=NS). Median age in ICT pts was 64 (range 32–70) years (y) vs. 78 (39–81)y for CP (p=0.04). Features of the 178 pts are previously reported. In a univariate analysis (n=178), factors significant for LFS were: MDS subtype; IPSS risk; increased FL; total RBCU transfused; ≥1 serious infection; and receipt of ICT (all p<0.05). Factors significant for LFS in a multivariate analysis (n=178) were: IPSS score (p=0.0001) and receipt of ICT (p=0.03). For low and int-1 IPSS, median LFS was not reached (NR) at 226 months (mo) for ICT pts and 40 mo for non-ICT pts (n=76) and 4y LFS was 64% and 42% respectively (p=0.002). In the subgroup analysis comparing ICT pts to 18 CP with matched features, at a median FU of 51.4 (7.1–225.8) mo and 44.8 (10.1–224) mo respectively, median LFS was NR at 226 mo vs. 40 mo in CP, and 4y LFS was 64% and 49% respectively (p=0.009). Median OS for ICT pts was NR at 226 mo vs. 40.5 mo for CP, and 4y OS was 64% and 49% respectively (p=0.01). There were 5 deaths (28%) in ICT pts (cardiac/IOL, n=2; infection, n=1; other MDS-related, n=1; AML, n=1) and 15 (83%) in CP (other MDS-related, n=6; AML, n=4; bleeding, n=2; infection, n=2; MDS-unrelated, n=1). Although non-ICT pts were older, only 1 death was age-related and all others were from MDS. One ICT pt developed AML at 15 mo from MDS Dx as did 4 non-ICT pts (p=0.06) at a median of 35 (19–71) mo; 2 pts received chemotherapy and both died of progressive AML. In ICT pts, mean ± standard error of the mean (sem) initial/pre-ICT FL was higher than in CP (4038±627 vs. 1759±1108 ug/L respectively, p=0.09), and FU levels decreased for ICT pts (3070±411, p=0.09) but not for CP (2185±996 ug/L, p=NS). There was no difference between ICT pts and CP in mean ± sem initial (2.0±0.3 and 2.0±0.5) and FU (3.4±0.9 and 7.4±4) x109/L NC; initial (236±32 and 104±25) and FU (164±24 and 82±20) x109/L PLTC; or initial (2.6±0.3 and 3.0±0.5) and FU (4.2±0.5 and 4.3±0.9) RBC-TR (no RBCU/4wk; all p=NS). In conclusion, LFS and OS in MDS pts with IOL receiving ICT were improved compared to non-ICT control pts matched for baseline features. These results support findings in the larger cohort of MDS pts and suggest there may be a beneficial effect of ICT on AML transformation and OS. Prospective studies of ICT in MDS pts are warranted.