1. Controversies in Iron Chelation in Myelodysplastic Syndromes
Aristoteles Giagounidis, MD, PhD Department of Haematology and Oncology St. Johannes Hospital Duisburg, Germany
Heather A. Leitch, MD, PhD, FRCPC Hematologist Department of Medicine, Division of Hematology St. Paul’s Hospital University of British Columbia Vancouver, British Columbia, Canada 1 1

2. Iron Overload and Transfusion Dependency Independent Impact on Overall Survival and Leukaemic Evolution in 902 Patients with MDS
HR P Value
Overall survival
Iron overload <.0001
Transfusion dependency <.0001
Risk for evolution to AML
Iron overload <.0001
Transfusion dependency <.003
Sanz G, et al. 50th Annual ASH Meeting; December 6-9, Abstract 640.

3. Independent Predictors of Survival in MDS
Median Survival P value
Transfusion-
Dependent mos <.001
Independent mos
Ferritin
High (>1,000 ng/mL) 34 yrs <.001
<1, yrs
Arnan M, et al. 15th Congress of EHA, June Abstract 314.

4. Nonleukaemic Causes of Death in MDS and Relationship to Iron Overload
Cardiac failure (CHF) 51%
Infection 31%
Haemorrhage %
Hepatic cirrhosis 8%
Unidentified 2%
Low-risk MDS: Cardiac failure is significantly more common in transfused than nontransfused patients (P=.01)
Malcovati L, et al. J Clin Oncol. 2005;23:

5. Iron Chelation and Overall Survival in Low/Int-1 MDS
Median overall survival
No chelation therapy – 53 mos
Chelation therapy – 124 mos
(p<.0003)
Adequate chelation was the strongest factor associated with better overall survival in heavily transfused lower risk MDS patients
97 low or int-1 IPSS regularly transfused patients:
44 (45%) not chelated; 53 (55%) chelated for >6 mos
Rose C, et al. Leuk Res. 2010;34:

6. Hematologic Improvement in MDS Patients with Iron Chelation Therapy
Pts with Minor
Erithroid Response*
After 6 mos 1/8
After 9 mos 2/8
After 12 mos 2/8
Total response rate 5/8 (60%)
8 MDS patients received
● Deferasirox 5-20 mg/kg/day, or
● Desferrioxamine 30 mg/kg/sc 3-4 times/week
*Minor response = 50% reduction in RBC transfused
Molteni A, et al. 15th Congress of EHA, June Abstract 1410.

7. 2008 Consensus Statement on Iron Overload in MDS
Transfusion-dependent patients
Ferritin levels >1000 ng/mL
Low-risk MDS (IPSS low or Int-1; WHO RA and RARS and 5q-)
Expected overall survival ≥1 year
Candidates for allograft
Need to preserve organ function
Absence of comorbidities severely limiting prognosis
Patients most likely to benefit from the treatment of iron overload
This is a profile of patients who might benefit from the treatment of iron overload.
The patient must be transfusion-dependent and should have a low-risk MDS, which means an IPSS score of low or intermediate-1.
This usually corresponds to the WHO-types of RA, RARS, and 5q- syndrome.
Irrespective of their FAB- or WHO-type, patients who are candidates for allografting may also be candidates for iron-chelation therapy, because it is important to avoid iron-related organ damage in patients who will undergo allogeneic transplantation.
Patients with an unfavourable FAB or WHO ype of MDS should not be excluded if they have documented stable disease.
Ferritin levels should be above 1000 or 2000 ng/ml, or, in cases where the ferritin is suspected to be unreliable, there should be other evidence of significant tissue iron overload.
The profile also requires the absence of comorbidities severely limiting prognosis, because such comorbidities would not allow the patient to live long enough to develop a substantial degree of iron overload.
Bennett JM, et al. Am J Hematol. 2008;83:

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