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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.

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Controversies in Iron Chelation in Myelodysplastic Syndromes

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  1. Aristoteles Giagounidis, MD, PhDDepartment of Haematology and OncologySt. Johannes Hospital Duisburg, Germany Heather A. Leitch, MD, PhD, FRCPCHematologistDepartment of Medicine, Division of HematologySt. Paul’s HospitalUniversity of British ColumbiaVancouver, British Columbia, Canada Controversies in Iron Chelation in Myelodysplastic Syndromes

  2. Iron Overload and Transfusion Dependency Independent Impact on Overall Survival and Leukaemic Evolution in 902 Patients with MDS HRP Value • Overall survival • Iron overload 52.4 <.0001 • Transfusion dependency 8.8 <.0001 • Risk for evolution to AML • Iron overload 6.6 <.0001 • Transfusion dependency 3.5 <.003 Sanz G, et al. 50th Annual ASH Meeting; December 6-9, 2008. Abstract 640.

  3. Independent Predictors of Survival in MDS Median SurvivalP value Transfusion- Dependent 34 mos <.001 Independent 56 mos Ferritin High (>1,000 ng/mL) 34 yrs <.001 <1,000 53 yrs Arnan M, et al. 15th Congress of EHA, June 2010. Abstract 314.

  4. Nonleukaemic Causes of Death in MDS and Relationship to Iron Overload • Cardiac failure (CHF) 51% • Infection 31% • Haemorrhage 8% • 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;23:7594-7603.

  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;34:864-870.

  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 2010. Abstract 1410.

  7. 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 2008 Consensus Statement on Iron Overload in MDS Patients most likely to benefit from the treatment of iron overload Bennett JM, et al. Am J Hematol. 2008;83:858-861.

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