Improved survival outcomes and restoration of graft‐vs‐leukemia effect by deferasirox after allogeneic stem cell transplantation in acute myeloid leukemia

Abstract

Deferasirox is an oral iron‐chelating agent having possible antileukemia and immune modulatory effects. Few reports have evaluated deferasirox in the setting of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). We investigated the impact of deferasirox after allo‐HSCT in acute myeloid leukemia (AML). Of 326 consecutive patients undergoing allo‐HSCT in remission, analysis of 198 patients not receiving deferasirox revealed the negative prognostic effect of hyperferritinemia (≥1000 ng/mL) before and after allo‐HSCT on survival mainly due to increase in relapse. Of 276 patients with hyperferritinemia at 1 month after allo‐HSCT, 128 patients (46%) received deferasirox. Deferasirox induced a faster decline in serum ferritin level with a manageable safety profile, which significantly reduced relapse rather than nonrelapse mortality, resulting in better survival compared to patients not receiving deferasirox. Of note, the deferasirox group had a significantly higher incidence of chronic graft‐vs‐host disease, indicating improved graft‐vs‐leukemia (GVL) effects evidenced by the presence of suppressed regulatory T cells and sustained higher proportion of NK cells in peripheral blood. This study firstly demonstrates the improved survival and restoration of GVL effects of patients with AML by deferasirox, which also clarifies the detrimental effect of hyperferritinemia through after allo‐HSCT.

Hyperferritinemia in patients with COVID‐19: An opportunity for iron chelation?

“…Others have also showed that elimination of iron by chelators improved outcome in different hyperferritinemic situations. For example, the oral iron chelator deferasirox improved survival outcomes and restored graft‐versus‐leukemia effect in patients with hyperferritinemia after allogeneic stem cell transplantation in acute myeloid leukemia 21 . In addition, DFO has been tried against a range of viral and parasitic infections since replication may be influenced by iron accumulation (Table 1).…”

Iron and leukemia: new insights for future treatments

“…A pilot clinical trial showed that DFO administration prior to allo-HSCT in patients with AL or MDS resulted in good outcomes, with no death or relapse, at a median follow-up of 20 months [110]. Similarly, a retrospective observational study of 339 patients demonstrates that the oral chelator DFX significantly reduces relapse mortality and restores graft-vs-leukemia effects (GVL) after allo-HSCT in AML, which is evidenced by high proportion of NK cells and suppressed regulatory T cells in peripheral blood [111]. Importantly, studies have shown that DFX, at concentrations equal to those clinically used or even at higher ones, has no harm to the viability of normal HSCs [85, 112].…”

Deferasirox induces cyclin D1 degradation and apoptosis in mantle cell lymphoma in a reactive oxygen species‐ and GSK3β‐dependent mechanism

“…Indeed, we confirmed the selectivity and safety of DFX and demonstrated that DFX had no cytotoxic effect on PBMCs obtained from healthy donors. In fact, the clinical use of DFX was reported to improve hematopoiesis in patients with myelodysplastic syndrome (MDS) and to enhance haematopoietic recovery, outcome and survival in patients after allogenic haematopoietic stem cell transplantation 42,43 …”