Relationship Between Total Iron Removed by Phlebotomy and Iron Removed From the Liver in Pediatric Thalassemia Major Patients Following Curative Stem Cell Transplant

Abstract

Abstract 5300 Background:Patients with thalassemia major (TM) who have undergone hematopoietic stem cell transplantation (HSCT) often demonstrate iron overload due to their previous requirement for regular blood transfusions, and are therefore at risk of associated toxicities. Efficient iron removal in such patients is therefore essential to prevent complications. For patients post-HSCT who undergo iron removal with phlebotomy, analysis of liver volume in combination with measurement of liver iron concentration (LIC) by MRI enables a calculation of total liver iron content (TLIC) in units of g Fe (in contrast to LIC in units of mg Fe/g tissue) both before and after phlebotomy. The aim of the study was to determine the average fraction of the Hb iron removed represented by the reduction in TLIC. Methods:LB03T is a prospective, randomized trial enrolling children aged 2-<18 years with TM who had undergone HSCT. Patients were chelation-naïve, hepatitis B- and C-negative, with confirmed iron overload (serum ferritin ≥500 ng/mL on ≥2 monthly occasions, and LIC >3 mg Fe/g dry weight [dw]). Eligible patients were randomized to phlebotomy (6 mL/kg blood/2 weeks) or deferasirox (10 mg/kg/day starting dose; 5 mg/kg/day adjustments up to 20 mg/kg/day were permitted). A primary study endpoint was change in LIC assessed using spin-density projection assisted R2-MRI (FerriScan®). For the patients undergoing phlebotomy, liver iron content was calculated as [liver volume] × [LIC]. A wet to dry weight conversion factor (3.8) was then applied, to transform the LIC into units of mg Fe/g wet tissue. The density of liver tissue was assumed as 1.051 g/mL, from which the TLIC was estimated. TLIC was calculated before and after phlebotomy to reduce iron overload, which enabled the total iron reduction in the liver to be calculated. Results:A total of 27 patients were randomized to deferasirox (n=12) or phlebotomy (n=14). One patient randomized to phlebotomy refused treatment. The results presented here refer to the patients in the phlebotomy arm only. The median time between MRI scans was 405 days (range: 254–632). The initial median LIC and TLIC were 7.4 (range: 3.1–24.0) mg/g dw and 2.6 (range: 0.6–7.4) g. Thirteen of the 14 subjects showed a response to phlebotomy therapy with LIC and TLIC decreasing with phlebotomy therapy. One subject (LIC 24.0 mg/g dw and TLIC 7.4 g) did not respond to phlebotomy therapy and showed an increase in both LIC and TLIC to 33.5 mg/g dw and 10.95 g respectively over a period of 425 days. For the 13 subjects who responded to phlebotomy therapy, there were significant correlations between reduction in LIC and grams of Hb iron phlebotomized (r2=0.41; P=0.02) and between reduction in TLIC and grams of Hb iron phlebotomized (r2=0.79; P<0.0001) (see Figure 1). The mean fraction of the phlebotomized Hb iron represented by the reduction in TLIC for the 13 responders was 71%. [Display omitted] Conclusions:Liver volume data combined with LIC measured by MRI enables a calculation of TLIC. In pediatric post-HSCT patients with TM undergoing phlebotomy, a significant linear correlation was found between reduction in TLIC and grams of Hb iron phlebotomized thereby rendering TLIC a useful and noninvasive tool for calculating the total body iron stores in this patient group. Disclosures:Inati:Novartis: Honoraria, Research Funding, Speakers Bureau. Taher:Novartis: Honoraria, Research Funding. St Pierre:Resonance Health: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties, Speakers Bureau.