Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements

Abstract

. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements. Annals of Hematology, Springer Verlag, 2009, 89 (2) Abstract The main objective of the study was to analyze the incidence of iron overload (IO) and its management in transfusion-dependent patients with low-risk myelodysplastic syndrome (MDS) before the license of deferasirox. This observational, cross-sectional, and multicenter study was conducted from January to May 2007 in 81 Spanish hospitals. Eligible patients had a low or intermediate-1 risk score and had to have received at least ten units of packed red blood cell (PRBC). Of the 549 patients analyzed, 75% had received more than 20 PRBC units since diagnosis; 14% had IO at diagnosis and 58% at last follow-up. Thirty-eight percent of patients received chelation therapy; of those, 92% were treated with desferrioxamine. Ferritin levels at the start of chelation therapy were higher than 1,000 μg/L in 76% and over 2,500 μg/L in 24% of patients. Of the 202 patients who received some form of chelation therapy, ferritin levels increased from a mean±SD of 1,986±1,398 to 2,480± 1,648 μg/L at last follow-up in 86% (p<0.001). In the remaining 29 patients treated with a minimally effective therapy, ferritin levels did not increase. Of these, only 11 patients received such therapy lasting more than 12 months. In conclusion, most low-risk transfusion-dependent MDS patients develop IO, but only a minority receives a minimally effective and timely iron chelation therapy.

Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes

“…This was higher than the 37.7% recently noted in a Spanish study [34], however these percentages are not exactly comparable. In the Spanish study, only patients with Low or Intermediate-1 MDS and with serum ferritin levels > 1000μg/L were considered for chelation, which moreover was by parenteral deferoxamine as deferasirox was not yet available in Spain.…”

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes

“…Most nonleukemic deaths were from cardiac and hepatic events as well as infections [3][4][5]. Increased leukemic progression in transfused versus nontransfused MDS patients was also observed retrospectively, though it is not clear whether this results from a worse underlying disease biology or reflects iron-mediated damage due to IO [19,20].…”

“…Evidence from registry studies and other observational sources suggests that patients with MDS and IO have worse survival and outcomes even after adjusting for transfusion burden [3][4][5], with increased rates of diabetes and glucose intolerance [4,19]. Most nonleukemic deaths were from cardiac and hepatic events as well as infections [3][4][5].…”

“…Retrospective data regarding effects of ICT on endorgan damage in MDS patients with IO are incon- sistent and subject to significant selection and other forms of bias [4][5][6][30][31][32]. Therapeutic decisions that affect patient outcome are not static and occur on an ongoing basis during the disease course in response to changes in the patient's condition, which may also influence survival.…”

“…Chronic RBC transfusion therapy places patients at significant risk of developing iron overload (IO) and its associated complications [1][2][3]. TD anemia leading to secondary IO has been associated with adverse clinical outcomes and adverse effects on survival in patients with MDS [3][4][5][6]. Although no randomized prospective data examining the impact of ICT on survival in MDS have been reported to date, iron chelation therapy (ICT) is commonly prescribed to MDS patients with TD anemia, especially patients with lowerrisk (LR) MDS [7,8].…”