General AML

Deferasirox improves survival outcomes and restores the graft-versus-leukemia effect following allogeneic stem cell transplantation in acute myeloid leukemia

The multifunctional protein, ferritin, has previously been shown to be involved in immunosuppression, angiogenesis and cell proliferation, with serum ferritin (SF) levels providing a promising option as a biomarker for patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).1,2 The role of hyperferritinemia, high ferritin levels, is unknown but may be associated with survival outcomes in the allo-HSCT setting.2 Deferasirox, an oral iron-chelating agent, has possible immunomodulatory effects and may be antileukemic, although the impact of deferasirox following allo-HSCT on survival in patients with acute myeloid leukemia (AML) is unknown.3

In this retrospective analysis, 339 consecutive patients with de novo AML who underwent un-manipulated allo-HSCT at a single center between January 2007 and February 2012 were evaluated, with patients achieving a complete response (CR) analyzed (n = 326; median age = 41 years; range, 18–66 years).4 Patients transplanted from matched siblings (54.9%), unrelated (33.7%), and haploidentical-related donors (11.3%) received myeloablative (65.3%) or reduced-intensity conditioning (34.7%). SF levels were monitored from the time of diagnosis of AML to 1, 3, 6, 9, and 12 months following allo-HSCT. Cohort one included patients not receiving deferasirox (n = 198), and aimed to assess the impact of hyperferritinemia prior to and following allo-HSCT on transplantation outcomes. In cohort two, patients had hyperferritinemia at one month post allo-HSCT (n = 276; 46% patients receiving deferasirox [n = 128]; 54% patients did not receive deferasirox [n = 148]), and aimed to assess the safety and efficacy of deferasirox.

Key findings:
  • In patients who did not receive deferasirox after allo-HSCT (cohort 1, n = 198)
    • Median SF level at pre-transplantation was 1383 ng/mL (range, 132–12,386)
    • SF levels peaked at 1-month post-allo-HSCT followed by a slow decrease
    • Median follow-up of 38 months (range, 1.0–99.6)
    • The high SF group at pre-transplantation had inferior overall survival (OS) and disease-free survival rates compared to the low SF group (48.6% vs 71.5%, P = 0.002; 46.6% vs 73.2%, P = 0.003), respectively
  • In patients with hyperferritinemia 1 month after allo-HSCT (cohort 2, n = 276)
    • Median time of deferasirox administration following allo-HSCT: 30 days (range, 28–50)
    • Median duration of deferasirox treatment: 5.4 months (range, 1.0–13.1)
    • Median follow-up of 40.7 months (range, 0.8–99.6)
    • Patients receiving deferasirox had superior OS and DFS compared to patients who did not receive deferasirox (66.6% vs 50.1%, P < 0.001; 65.4% vs 47.5%, P < 0.001), respectively
    • No significant difference between the occurrence of grade II-IV acute graft-versus-host disease in patients receiving or not receiving deferasirox, respectively: 27.3% vs 25.7%, P = 0.532

The authors concluded that this study demonstrates the negative prognostic role of hyperferritinemia prior to and following allo-HSCT in patients with AML, mainly due to the graft-versus­-leukemia effect. However, due to the retrospective nature of this analysis, further prospective, controlled, randomized trials are needed to explore the impact of deferasirox post-allo-HSCT in AML.

References
  1. Alkhateeb A.A. et al. The significance of ferritin in cancer: anti-oxidation, inflammation and tumorigenesis. Biochim Biophys Acta. 2013 Dec; 1836(2): 245–254. DOI: 10.1016/j.bbcan.2013.07.002.
  2. Trottier B.J. et al. Association of iron overload with allogeneic hematopoietic cell transplantation outcomes: a prospective cohort study using R2-MRI-measured liver iron content. Blood. 2013 Aug 29; 122(9): 1678–1684. DOI: 10.1182/blood-2013-04-499772.
  3. Vallejo C. et al. Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation. Haematologica. 2014 Oct; 99(10): 1632–1637. DOI: 10.3324/haematol.2014.105908.
  4. Cho B.S. et al. Improved survival outcomes and restoration of graft-vs-leukemia effect by deferasirox after allogeneic stem cell transplantation in acute myeloid leukemia. Cancer Med. 2019 Jan 24. DOI: 10.1002/cam4.1928. [Epub ahead of print]
Download this article:

You can now download this article in Adobe PDF® format.

Download as PDF
Was this article informative? Thank you for your feedback!