A prospective non-interventional study on the impact of transfusion burden and related iron toxicity on outcome in myelodysplastic syndromes undergoing allogeneic hematopoietic cell transplantation

Abstract

Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p ¼ .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p ¼ .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT – A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

“…Interestingly, a recent prospective study in patients with MDS and CMML undergoing alloSCT reported that administration of iron chelation therapy prior to HSCT was not associated to outcome. However, early iron reduction after alloSCT (started before d + 180) was associated to improved relapse free survival (29).…”

How to manage iron toxicity in post-allogeneic hematopoietic stem cell transplantation?

“…Many allogeneic HCT patients especially with myelodysplasia and leukemia are not transfusion-independent following transplantation and chelation therapy may be necessary for the removal of IO. The decisions on chelating drug dose protocols are usually based on a risk/benefit assessment including complications of the underlying disease, drug toxicity, and quality-adjusted life years [16,17].…”

“…Most of these protocols involve the administration of DF, L1, and the DF/L1 combinations, which have been used for more than 20 years in the treatment of IO [5]. Several studies using DFRA suggest that it can also be used in post-allogeneic HCT patients despite that other investigators reported serious toxicities and discontinuation of chelation treatment [16][17][18][19][20][21]. The level of toxicity of chelation therapy by DFRA, L1, and DF in HCT patients is expected to be similar to that reported for other categories of iron-loaded patients [5].…”

“…Variable effects of DF, DFRA, and L1 are generally observed in iron-loaded patients. Each chelating drug has a different mode of action, efficacy, toxicity, and cost, which overall affects the morbidity and mortality of post-allogeneic HCT and other iron-loaded patients [5,[16][17][18][19][20][21].…”

Antioxidant Activity of Deferasirox and Its Metal Complexes in Model Systems of Oxidative Damage: Comparison with Deferiprone

“…There are hundreds of thousands of iron overloaded patients belonging to different categories of inherited and other diseases, who receive regular red blood cell transfusions for the treatment of their refractory anemia [ 1 , 2 , 3 ]. Iron overload is considered as an independent adverse prognostic factor in all diseases.…”