Safety and Efficacy of Iron Chelation with Deferasirox in Adult Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Jeon Young-Woo , Cho Byung-Sik , Kim Hee-Je , Yoon Jae-Ho , Shin Seung-Hwan , Lee Sung-Eun , Eom Ki-Seong , Kim YooJin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Kim Dong-Wook , Lee Jong-Wook , Min Woo-Sung 
Published: October 2019

Background

The prognostic impact of serum ferritin level has been well established in patients with myelodysplastic syndrome and acute myeloid leukemia (AML) in the context of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, the clinical safety and efficacy of iron-chelation therapy (ICT) for adult AML with hyperferritinemia post-Allo-SCT has not been evaluated.

Materials and methods

We retrospectively evaluated 320 consecutive patients with de novo AML who received Allo-HSCT at complete remission in a single institution between January 2007 and February 2012. Serum ferritin levels were monitored from initial diagnosis to the several time points during the post-transplantation period in both the ICT group (n=113) and the non-treated group (NT, n=191). In the ICT group, ICT was started at least a month after transplantation when serum ferritin levels over 1,000 ng/mL, and continued to the ferritin level lower than 500 ng/ml unless serious adverse effects and/or relapse. Sixteen patients treated less than one month with ICT due to early complications, such as infection(n= 10, 62.5%), liver toxicity (n=4, 25%), and poor compliance (n=2, 12.5%) were excluded in the ICT group. The baseline characteristics between two groups were not significantly different.

Results

The median treatment duration in ICT group was 6.4 months (range, 1.0-49.2) with dosage of 20-40 mg/kg/day. Deferasirox treatment was discontinued at least one time in 43 patients (38%) in ICT group due to toxicities and/or poor compliance, but almost patients (n=40, 93%) could be treated again with deferasirox without further toxicities. High serum ferritin level of pre-Allo-HSCT over 1,000 ng/ml was significantly associated with poor overall survival (OS, 52.2% vs. 75.4%, HR 0.78, P <0.001) and lower chronic graft-versus-host disease (GVHD, 53.3% vs. 74.6%, HR 0.83, P =0.001). With a median follow up of 40.2 months, OS, disease-free survival (DFS), and cumulative incidence of relapse (CIR), non-relapse mortality, acute (over grade II) and chronic GVHD were 62.7%, 63.7%, 11.6%, 5.9%, 24.4% and 42.8%, respectively. On multivariate analyses, ICT group had significantly lower CIR (25.9% vs. 37%, HR 0.65, P=0.011) and higher cumulative incidence of chronic GVHD (46% vs. 20.1%, HR 1.88 P<0.001), with a trend of superior survival (OS, 72.0% vs 63.4%, P=0.053; DFS, 70.3% vs 61.4 %, P=0.058), whereas no association with acute GVHD (P=0.473)

Conclusion

Our data demonstrate that ICT with deferasirox was well tolerable in AML with hyperferritinemia after Allo-SCT, and suggest the independent association of ICT with increased incidence of chronic GVHD and decreased relapse. Iron chelation may modulate of immunobiologic properties during the period of immune reconstitution (low level of Treg cells and higher CD16+ NK cells, 2014 ASH Abstract #2543) and/or induce direct anti-leukemia effect by iron depletion, which need to be further evaluated.

Disclosures

No relevant conflicts of interest to declare.