Contributions
Abstract: PB2289
Type: Publication Only
Background
Anaemia is a major problem in myelofibrosis (MF). The cause of anaemia is not completely understood. Recent studies have shown inflammatory activity in myelofibrosis. Inflammation influences iron metabolism. Cytokines upregulate hepcidin, causing a retention of iron in macrophages. This leads to sequestration of iron in the macrophages, a lowered transferrin saturation and reduced availability of iron for erythropoiesis. This is named functional iron deficiency (FID) and in malignancy is characterized by transferrin saturation (TSAT) <20% and a normal or elevated S-ferritin. FID is common in malignancies and is treatable with intravenous iron.
Aims
We aimed to investigate if FID and inflammation are common in MF and whether they may contribute to anaemia and influence Quality of life (QoL).
Methods
We recruited 80 patients with MF, 22 with ET (JAK2V617 was found in 60 and 61% in MF and ET, respectively) from 6 centers in the Nordic area. Blood values, iron variables and inflammatory markers were analyzed. Quality of life was investigated with MPN-SAF.
Results
MF
53 of the 80 MF patients were anaemic (Hb <120 g/L in women, <130 g/L in men). 14 of these were transfusion dependent with haemosiderosis (S-ferritin >500 mg/L). These were excluded from the analysis of FID. Among the rest of the anaemic patients (n=39) FID (TSAT < 20%, S-ferritin <500 ug/L) was found in 35% vs. 23.8 % of non-anaemic (NS). In MF patients with FID, 70.6 % were anaemic, vs. 29.4 % in patients with TSAT >20 (p=0.3) . Among non-anaemic MF patients, 23.8% had a TSAT <20%, vs. 35.3% of the anaemic patients. Hepcidin was significantly higher in patients with anaemia, 50.6 vs 24,4 mg/L (p=0,01). 51 % of women with MF had increased hepcidin levels vs. 9% in men. There was a significant negative correlation between Hb and inflammatory markers in MF patients :TNFα, IL-6 and CRP(p <0.01 to 0.02), also LD (p=0.004) and Hepcidin (p=0.03). TSAT correlated with CRP (p<0.001). In all MF patients, hepcidin was higher in patients with S-ferritin >500 mg/L (p<0.001), as was IL-6 (p= 0.02), IL-2 (p= 0.03), and CRP(p= 0.001). For the whole group (MF+ET) there was a correlation between TSAT and QoL scores (Brief fatigue inventory (BFI) p=0.03, Total symptom score (TSS) p=0.002) as well as between inflammatory markers IL-6 and CRP and QoL scores(p=0.002 – 0.02 for BFI, overall QoL and TSS). Cytokine levels (IL-2, IL-6, TNFα and CRP) correlated positively with hepcidin (p values <0.001 to 0.01) in the whole group (MF+ET)
ET
In ET patients, TSAT was below 20% in 4 patients, but 3/4 had S-ferritin in the low range, indicating iron deficiency. The one ET patient with anaemia had a true iron deficiency with low S-ferritin. Only one ET patient with low TSAT could be classified as FID.
Conclusion
FID is common in MF but not in ET and patients with FID are more likely to be anaemic. MF is an inflammatory state and Hb correlated negatively with cytokine and hepcidin levels. Cytokine levels correlated positively with hepcidin. The inflammatory activity and TSAT correlated with QoL. Our results indicate that the inflammatory state of MF disturbs iron turnover and contributes to anaemia development and impairment of QoL. FID should be sought for in anaemic MF patients. It is possible that MF patients with FID like other cancer patients may respond to IV iron.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Anemia, inflammation, iron deficiency, Myelofibrosis
Abstract: PB2289
Type: Publication Only
Background
Anaemia is a major problem in myelofibrosis (MF). The cause of anaemia is not completely understood. Recent studies have shown inflammatory activity in myelofibrosis. Inflammation influences iron metabolism. Cytokines upregulate hepcidin, causing a retention of iron in macrophages. This leads to sequestration of iron in the macrophages, a lowered transferrin saturation and reduced availability of iron for erythropoiesis. This is named functional iron deficiency (FID) and in malignancy is characterized by transferrin saturation (TSAT) <20% and a normal or elevated S-ferritin. FID is common in malignancies and is treatable with intravenous iron.
Aims
We aimed to investigate if FID and inflammation are common in MF and whether they may contribute to anaemia and influence Quality of life (QoL).
Methods
We recruited 80 patients with MF, 22 with ET (JAK2V617 was found in 60 and 61% in MF and ET, respectively) from 6 centers in the Nordic area. Blood values, iron variables and inflammatory markers were analyzed. Quality of life was investigated with MPN-SAF.
Results
MF
53 of the 80 MF patients were anaemic (Hb <120 g/L in women, <130 g/L in men). 14 of these were transfusion dependent with haemosiderosis (S-ferritin >500 mg/L). These were excluded from the analysis of FID. Among the rest of the anaemic patients (n=39) FID (TSAT < 20%, S-ferritin <500 ug/L) was found in 35% vs. 23.8 % of non-anaemic (NS). In MF patients with FID, 70.6 % were anaemic, vs. 29.4 % in patients with TSAT >20 (p=0.3) . Among non-anaemic MF patients, 23.8% had a TSAT <20%, vs. 35.3% of the anaemic patients. Hepcidin was significantly higher in patients with anaemia, 50.6 vs 24,4 mg/L (p=0,01). 51 % of women with MF had increased hepcidin levels vs. 9% in men. There was a significant negative correlation between Hb and inflammatory markers in MF patients :TNFα, IL-6 and CRP(p <0.01 to 0.02), also LD (p=0.004) and Hepcidin (p=0.03). TSAT correlated with CRP (p<0.001). In all MF patients, hepcidin was higher in patients with S-ferritin >500 mg/L (p<0.001), as was IL-6 (p= 0.02), IL-2 (p= 0.03), and CRP(p= 0.001). For the whole group (MF+ET) there was a correlation between TSAT and QoL scores (Brief fatigue inventory (BFI) p=0.03, Total symptom score (TSS) p=0.002) as well as between inflammatory markers IL-6 and CRP and QoL scores(p=0.002 – 0.02 for BFI, overall QoL and TSS). Cytokine levels (IL-2, IL-6, TNFα and CRP) correlated positively with hepcidin (p values <0.001 to 0.01) in the whole group (MF+ET)
ET
In ET patients, TSAT was below 20% in 4 patients, but 3/4 had S-ferritin in the low range, indicating iron deficiency. The one ET patient with anaemia had a true iron deficiency with low S-ferritin. Only one ET patient with low TSAT could be classified as FID.
Conclusion
FID is common in MF but not in ET and patients with FID are more likely to be anaemic. MF is an inflammatory state and Hb correlated negatively with cytokine and hepcidin levels. Cytokine levels correlated positively with hepcidin. The inflammatory activity and TSAT correlated with QoL. Our results indicate that the inflammatory state of MF disturbs iron turnover and contributes to anaemia development and impairment of QoL. FID should be sought for in anaemic MF patients. It is possible that MF patients with FID like other cancer patients may respond to IV iron.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Anemia, inflammation, iron deficiency, Myelofibrosis