Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Abstract

BackgroundReductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on these reductions/improvements have been limited to case reports and small studies. Design and MethodsTo explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients' Iron Chelation with Exjade ® (EPIC) study using International Working Group 2006 criteria. ResultsTwo-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders. ConclusionsThis analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.Key words: myelodysplastic syndromes, deferasirox, iron overload, iron chelation therapy, hematologic response. Haematologica 2012;97(9):1364-1371. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Gattermann N, Finelli C, Della Porta M, Fenaux P, Stadler M, Guerci-Bresler A, Schmid M, Taylor K, Vassilieff D, Habr D, Marcellari A, Roubert B, and Rose C. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Efficacy and safety of deferasirox in non-thalassemic patients with elevated ferritin levels after allogeneic hematopoietic stem cell transplantation

“…37,38 The early improvement in Hb under deferasirox is comparable to that described in patients with MDS and may be because of improved hematopoiesis. 39,40 It has been shown that chelation with deferasirox leads to rapid reduction of the deleterious labile plasma iron, thereby ameliorating the damage caused by reactive oxygen species within RBCs. 41,42 The improvement in hematopoiesis under chelation reduces the inhibitory effect of suppressed erythropoiesis on hepcidin and thus may, at least partially, explain the early upsurge in urinary hepcidin similar to that observed in MDS.…”

Iron overload in myelodysplastic syndromes (MDS)

“…List et al [27] Low/lnt-1 15% (n = 173) 15% (n = 52) 22% (n = 77) Gattermann et al [28] Low/lnt-1 21.5% (n = 247) 22% (r = 50) 13% (n = 100) Nolte et al [29] Low/lnt-1 11% (n = 50) NR NR Angelucci et al [30] Low/lnt-1 Transfusion independence in 15.5% (n = 152) Table 2 Clinical studies showing that iron chelation improves survival in patients with lower risk MDS [32][33][34][35][36][37][38][39][40].…”

“…Erythroid response rates range between 11 and 22%. Table 1 Clinical trials showing erythropoietic improvement during iron chelation therapy in patients with lower risk MDS [27][28][29][30].…”

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

“…Wspomniani chorzy na MDS nie byli leczeni innymi metodami, przewidywane u nich OS przekraczało rok i stwierdzono u nich IO [54]. Odpowiedź czerwonokrwinkową, płytkową i neutrofilową, zgodnie z oceną według Międzynarodowej Grupy Roboczej (IWG, International Working Group), obserwowano, odpowiednio, u 26,6%, 14% i 19,6% chorych na MDS, przez rok stosowania leczenia deferazyroksem [55].…”