Summary of studies assessing the impact of transfusion dependence, iron overload and iron chelation therapy on clinical parameters in MDS patients in the usual (non-transplant) clinical setting.
| . | . | . | Transfusion dependence HR . | Iron overload HR . | Iron chelation therapy HR . | . | . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Study . | n . | Reference population . | OS . | LFS . | OS . | LFS . | OS . | LFS . | Comments . | Ref . |
| 1Comparison group non-transfusion dependent patients (0 RBCU/4 wks) without | ||||||||||
| 2Comparison group low/int-1 IPSS risk not receiving iron chelation therapy | ||||||||||
| 3Comparison group, patients who did not receive chelation | ||||||||||
| 4Comparison group RARS, for TD, non-TD; for IOL, ferritin <1000 compared to ≥ 1000, and compared to 1000–5000 and >5000 | ||||||||||
| 5Comparison group for transfusion dependence, requiring <1 RBCU/4 wk; for IOL, ferritin ≤ 1000 ng/mL | ||||||||||
| 6Comparison group Hb>10 g/dL | ||||||||||
| 7Comparison group, intermittent ICT patients; of deaths, 24% were from CHF and 6.7% excess blasts from liver-related causes | ||||||||||
| 8Japanese units are smaller than North American units, usually derived from 200 mL of whole blood | ||||||||||
| 9Comparison group, controls were randomly selected from MDS non-cases (see footnote 10) | ||||||||||
| 10Complications of IOL, cases; cardiomyopathy/CHF, conduction/rhythm disorders, diabetes, liver disease | ||||||||||
| ALT indicates alanine aminotransferase; AN, anemia; aprx, approximately; AST, aspartate aminotransferase; CHF, congestive heart failure; int, intermediate; DFO, deferoxamine; DM, diabetes mellitus; inter, intermittent; GFM, Groupe Francophone des Myelodysplasies; Hb, hemoglobin; HR, hazard ratio; ICT, iron chelation therapy; IMRAW, International MDS Risk Analysis Workshop; IOL, iron overload; IPSS, International Prognostic Scoring System; LFS, leukemia-free survival; MDS, myelodysplastic syndrome; Med, median; ng, nanogram; NS, not significant; OR, odds ratio; OS, overall survival; RARS, refractory anemia with ring sideroblasts; RBC, red blood cell; STD, standard; TD, transfusion dependence; U, unit(s); US, United States | ||||||||||
| Pavia1 | 467 | Without excess blasts | 1.91 1.36/RBCU/4 wks P < .001 | 1.84 1.40/RBCU/4 wks P < .001 | 1.42 per 500 ng/mL P < .001 | – | – | – | IOL, ferritin ≥ 1000 ng/mL | 6,9 |
| Vancouver2 | 178 | IPSS low/int-1 ICT, n = 18 | – | – | – | – | 0.1 P = .02 | – | 4y OS 64% vs 43% | 14, 16 |
| GFM3 | 170 | IPSS low/int-1 ICT, n = 115 | – | – | – | – | P = .003 | – | Median OS (mo) STD ICT, 120 Low ICT, 69 No ICT, 50–69 | 15 |
| Mayo4 | 126 | RARS | P = .001 | – | NS | – | – | – | ICT, n = 15 | 7 |
| Sanz5 | 2884 | n = 902 | 8.8 | 3.5 | 52.4 | 6.6 | – | – | 10 | |
| IMRAW/IPSS6 | 816 | Int-1/Int-2 Hb ≤ 10.0 g/dL | P = .0001 | NS | - | - | - | - | MedOS aprx 1/2 AN vs TD vs IOL effect? | 8 |
| Japanese7 | 292 MDS, n = 152 | DFO, n = 126 8.6% continuous (91.4% intermittent) | Median NRBCU8 Died, n = 289.2 Alive, n = 160.7 P = .0033 | – | Died, n = 38 Ferritin >1000, n = 37/38 Ferritin >5000, n = 24 | – | – | – | Ferritin, AST, ALT decreased in continuous ICT pts P ≤ .005 | 34 |
| US insurance database9 | 4546 | 511 cases 511 controls | OR 2.90, P = .0008 For developing complications of IOL10 | – | – | – | – | – | Arrhythmia OR 4.18, P = .0005 DM OR 5.06, P = .0025 Liver OR 3.31, P = .0008 | 35 |
| . | . | . | Transfusion dependence HR . | Iron overload HR . | Iron chelation therapy HR . | . | . | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Study . | n . | Reference population . | OS . | LFS . | OS . | LFS . | OS . | LFS . | Comments . | Ref . |
| 1Comparison group non-transfusion dependent patients (0 RBCU/4 wks) without | ||||||||||
| 2Comparison group low/int-1 IPSS risk not receiving iron chelation therapy | ||||||||||
| 3Comparison group, patients who did not receive chelation | ||||||||||
| 4Comparison group RARS, for TD, non-TD; for IOL, ferritin <1000 compared to ≥ 1000, and compared to 1000–5000 and >5000 | ||||||||||
| 5Comparison group for transfusion dependence, requiring <1 RBCU/4 wk; for IOL, ferritin ≤ 1000 ng/mL | ||||||||||
| 6Comparison group Hb>10 g/dL | ||||||||||
| 7Comparison group, intermittent ICT patients; of deaths, 24% were from CHF and 6.7% excess blasts from liver-related causes | ||||||||||
| 8Japanese units are smaller than North American units, usually derived from 200 mL of whole blood | ||||||||||
| 9Comparison group, controls were randomly selected from MDS non-cases (see footnote 10) | ||||||||||
| 10Complications of IOL, cases; cardiomyopathy/CHF, conduction/rhythm disorders, diabetes, liver disease | ||||||||||
| ALT indicates alanine aminotransferase; AN, anemia; aprx, approximately; AST, aspartate aminotransferase; CHF, congestive heart failure; int, intermediate; DFO, deferoxamine; DM, diabetes mellitus; inter, intermittent; GFM, Groupe Francophone des Myelodysplasies; Hb, hemoglobin; HR, hazard ratio; ICT, iron chelation therapy; IMRAW, International MDS Risk Analysis Workshop; IOL, iron overload; IPSS, International Prognostic Scoring System; LFS, leukemia-free survival; MDS, myelodysplastic syndrome; Med, median; ng, nanogram; NS, not significant; OR, odds ratio; OS, overall survival; RARS, refractory anemia with ring sideroblasts; RBC, red blood cell; STD, standard; TD, transfusion dependence; U, unit(s); US, United States | ||||||||||
| Pavia1 | 467 | Without excess blasts | 1.91 1.36/RBCU/4 wks P < .001 | 1.84 1.40/RBCU/4 wks P < .001 | 1.42 per 500 ng/mL P < .001 | – | – | – | IOL, ferritin ≥ 1000 ng/mL | 6,9 |
| Vancouver2 | 178 | IPSS low/int-1 ICT, n = 18 | – | – | – | – | 0.1 P = .02 | – | 4y OS 64% vs 43% | 14, 16 |
| GFM3 | 170 | IPSS low/int-1 ICT, n = 115 | – | – | – | – | P = .003 | – | Median OS (mo) STD ICT, 120 Low ICT, 69 No ICT, 50–69 | 15 |
| Mayo4 | 126 | RARS | P = .001 | – | NS | – | – | – | ICT, n = 15 | 7 |
| Sanz5 | 2884 | n = 902 | 8.8 | 3.5 | 52.4 | 6.6 | – | – | 10 | |
| IMRAW/IPSS6 | 816 | Int-1/Int-2 Hb ≤ 10.0 g/dL | P = .0001 | NS | - | - | - | - | MedOS aprx 1/2 AN vs TD vs IOL effect? | 8 |
| Japanese7 | 292 MDS, n = 152 | DFO, n = 126 8.6% continuous (91.4% intermittent) | Median NRBCU8 Died, n = 289.2 Alive, n = 160.7 P = .0033 | – | Died, n = 38 Ferritin >1000, n = 37/38 Ferritin >5000, n = 24 | – | – | – | Ferritin, AST, ALT decreased in continuous ICT pts P ≤ .005 | 34 |
| US insurance database9 | 4546 | 511 cases 511 controls | OR 2.90, P = .0008 For developing complications of IOL10 | – | – | – | – | – | Arrhythmia OR 4.18, P = .0005 DM OR 5.06, P = .0025 Liver OR 3.31, P = .0008 | 35 |