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.
- 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.