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Recommendations

  • The literature guiding recommendations for treatment of IOL in MDS is suboptimal. Previous Canadian consensus recommendations are based mainly on BTM patients, though evidence in MDS has accumulated in the decade since the initial Canadian guidelines were published. IOL should be minimized or reduced wherever possible by using medications that produce erythroid responses in combination where appropriate with phlebotomy. Once the decision has been made to initiate ICT, either DFO or DFX may be used (evidence level II-2, recommendation grade B)1:
    • DFO 20–50mg/kg/day by continuous SQ or IV infusion over 12–24h (or by twice daily SQ bolus in select patients), 5-7 days/week, dosed to keep the therapeutic index (mean daily dose in mg/kg divided by SF) <0.025
    • DFX 20–30mg/kg PO daily for the DF (Exjade®), or up to 40mg/kg/day in select patients according to tolerance; the FCT (Jadenu®) because of increased GI absorption must be dosed at 30% less on a mg/kg basis than the DF, ie 14-20mg/kg PO daily, or up to 28mg/kg/day in select patients.
    • To avoid GI intolerance, DFX may be started at lower doses and titrated up.

Iron reduction endpoints

  • DFO should be discontinued at a ferritin level <1000 ng/mL due to an increased incidence of opthamologic & ototoxicity2
  • DFX may safer at ferritin <1000 ng/mL but this has not been definitively demonstrated3
  • For patients undergoing phlebotomy during a period of transfusion independence, reducing the ferritin into the low-normal range, as is done in hereditary hemochromatosis, could be considered4
  • Response criteria for IOL reduction have been proposed5