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.

• Authors: Byung-Sik Cho, Young-Woo Jeon, A-Reum Hahn, Tai-Hyang Lee, Sung-Soo Park, Jae-Ho Yoon, Sung-Eun Lee, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Jong-Wook Lee, Woo-Sung Min, Hee-Je Kim
• Journal: Cancer medicine (Cancer Med) Vol. 8 Issue 2 Pg. 501-514 (02 2019) ISSN: 2045-7634 [Electronic] United States
• PMID: 30677244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Iron Chelating Agents
• Ferritins
• Deferasirox

Topics

• Adolescent
• Adult
• Aged
• Deferasirox (therapeutic use)
• Female
• Ferritins (blood)
• Graft vs Leukemia Effect (drug effects)
• Hematopoietic Stem Cell Transplantation
• Humans
• Iron Chelating Agents (therapeutic use)
• Leukemia, Myeloid, Acute (blood, therapy)
• Male
• Middle Aged
• Treatment Outcome
• Young Adult