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IOL & organ endpoints


Studies examining iron overload and organ endpoints in transfusion dependent lower IPSS risk MDS patients.
Study N IOL measure Endpoint Findings Reference
Schaefer 1981 15 Median RBCU 120 organs Elevated LFTs (87%), portal fibrosis (66%), cardiomegaly (50%), CHF (27%), arrhythmias (53%), abnormal GTT (100%) [1]
Jaeger 1992 46 Median RBCU 79 organs Elevated LFTs (24%), cardiac siderosis (43%), CHF deaths (30%), arrhythmias (22%), DM (11%) [2]
Cazzola 1988 26 Median RBCU 64 organs Elevated LFTs (69%), CHF (31%), impaired GTT/DM (77%) [3]
Takatoku 2007 152 Median RBCU ≈ 100 organs Elevated LFTs (90%), hepatic failure (7%)*, CHF (24%)* [4]
Ferte 2006 21 Median RBCU 81 heart Cardiomegaly (43%), CHF (66%) [5]
*present at death. CHF, congestive heart failure; DM, diabetes mellitus; GTT, glucose tolerance test; IOL, iron overload; IPSS, International Prognostic Scoring System; LFT, liver function tests (transaminases); n, number; RBCU, red blood cell units; Modified from Wells RA, et al. Leuk Res. 2008;32:1338-53 and Leitch HA, et al. Leuk Res. 2018;74:21-41.
Studies examining organ endpoints in transfusion dependent patients with lower IPSS risk MDS by receipt of iron chelation therapy.
Study N Design Endpoint Non-chelated patients Chelated patients p value Reference
Jensen 20031 29 Observational Organ - hepatic NA Baseline ↑ ALT in 16 Normalized at 1y in 13 NR [1]
Jensen 19971 11 Observational Organ - cardiac NA Baseline ↑ cardiac iron in 8
Normalized at 6-10 mo in 10
NR [2]
Rose 2010 97 Prospective follow-up Cardiac mortality 34.5% 37% NS [3]
Remacha 2012, 2015 263 Retrospective Cardiac EFS 90 mo 137 mo 0.017 [4,5]
Lyons 20172 599 Prospective, registry New or progressive cardiac condition NR NR NS [6]
Gattermann 2012 71 Prospective, pooled data Organ – hepatic

LIC decrease >30%

Normal ALT
NA With baseline LIC ≥7 mg/gDW: 58.9%
71.4% at EOS vs 32.1% baseline
NR [7]
Wong 20183 151 Retrospective Time to cardiac event

MVA
7 mo 20 mo

HR for shorter TTCE
0.93
[95% CI 0.87-0.99]
0.02

0.03
[8] info
ALT, alanine aminotransferase; ARR, arrythmia; CAD, coronary artery disease; CHF, congestive heart failure; CM, comorbidities; CVS, cardiovascular; DFO, deferoxamine; DW, dry weight; EFS, event-free survival; EOS, end of study; HR, hazard ratio; IPSS, International Prognostic Scoring System; LIC, liver iron concentration; mo, months; MVA, multivariate analysis; N, number; NA, not applicable; NR, not reported; NS, not significant; TTCE, time to cardiac event; RBC, red blood cell; y, years. 1DFO. 2CHF or ARR. Similar results were seen in patients with & without concomitant CVS or endocrine CM. 3CHF, CAD or ARR. TTCE measured from first RBC transfusion dependence. Modified from Wells RA, et al. Leuk Res. 2008;32:1338-53 and Leitch HA, et al. Leuk Res. 2018;74:21-41.

1Schafer AI, et al. NEJM. 1981;304:319-24. 2Jaeger M, et al. Beitr Infusionsther. 1992;30:464-8. 3Cazzola M, et al. Blood. 1988;71:305-12. 4Takatoku M, et al. Eur J Haematol. 2007;78:487-94. 5Ferte C, et al. Blood. 2006;108:abstract 2666.

1Jensen PD, et al. Blood. 2003;101:91-6. 2Jensen PD, et al. Eur J Haematol. 1997;59:221-30. 3Rose C, et al. Leuk Res. 2010;34:864-70. 4Remacha AF, et al. Ann Hematol. 2015;94:779-87. 5Remacha A, et al. Blood. 2012;120:Abstract 1723. 6Lyons RM, et al. Leuk Res. 2017;56:88-95. 7Gattermann N, et al. Haematologica. 2012;97:abstract 344. 8Wong CAC & Leitch HA. Leuk Res. 2019; 83:106170.