Background: Chronic transfusion therapy (CTT) is a mainstay of prophylactic management and treatment for adults and children with high risk Sickle Cell Disease (SCD). We estimate that 10-20% of all adults with SCD managed at our centers, especially those with homozygous HbSS disease, are on CTT, for long-term management of cerebral vasculopathy, significant end organ damage, or chronic pain. Iron overload is a common complication of CTT and for patients receiving intermittent transfusion to treat acute complications. Each unit of transfused blood introduces approximately 250 mg of iron into the bloodstream, and with it, increased oxidative stress (A. Remacha, et al., “Guidelines on haemovigilance of post-transfusional iron overload,” Blood Transfusion, vol. 11, no. 1, pp. 128-139, 2013). High iron levels in the blood cumulatively lead to systemic iron deposition, particularly in the liver and heart, and untreated may lead to organ dysfunction or death. Patients with high iron levels should be put on iron chelation. Recent NHLBI guidelines suggest that patients on CTT be monitored for iron accumulation with quarterly ferritin levels, and annual or semiannual liver iron scans to assess hepatic iron burden, though the optimal frequency of these scans has not been established (B. P. Yawn, et al., “Management of Sickle Cell Disease: Summary of the 2014 Evidence-Based Report by Expert Panel Members,” JAMA, vol. 10, no. 312, pp. 1033-1048, 2014). We examined iron overload, its frequency, severity, and management, in a modern population of adults with SCD enrolled in the multi-center prospective sickle cell registry, Globin Research Network of Data and Discovery (GRNDaD).Methods: GRNDaD is a multi-site registry of both adult and pediatric SCD patients, currently accruing at 5 urban sickle cell centers, in Baltimore MD, Cleveland OH, Milwaukee WI, Columbus OH, and Oakland CA. It currently contains prospective baseline and annual update information on nearly 500 people with SCD. Additionally, approximately 150 more patients have consented, with data entry pending. The dataset comprises demographics as well as baseline and yearly lab values, complications, procedures, treatment, and vaccination history for each patient. Among these data are ferritin levels, liver iron scan results, and chelation therapy information. We analyzed ferritin levels in people with SCD, relative to genotype, age, gender, treatment type, liver iron scan results, and chelation therapy history.Results: There were 402 adults (age≥18 years) in GRNDaD who had a non-crisis ferritin level from a routine follow-up visit. This included people with phenotypic homozygous SCD (HbSS, n=255 and Sβ0 thalassemia, N=13), variant SCD (HbSC, n=80, or Sβ+ thalassemia, n=37), and other or unknown genotypes (n=17, Table 1). Nearly 3 in 10 of all patients with SCD (n=118, 29.3%) had a ferritin level at baseline ≥1500 mg/dL, which is an accepted threshold above which to initiate chelation. Most people with an elevated ferritin had phenotypic SCA (homozygous Hb S) (n=111, or 94%). Over half of all SCD patients with a critically elevated ferritin were on CTT (n=64, 54%), and a similar number of people with SCD and critical ferritin levels were on chelation (n=64, 54%). Less than 1 in 4 had had a liver iron scan within 3 years (n=27, 23%). More than 1 in 3 patients with critical ferritin levels and no chelation therapy remained on CTT (n=21, not shown).Conclusions: Our multi-site registry, GRNDaD, prospectively surveyed a sizable population of adults with SCD, including data about iron overload. Of the adults in the GRNDaD registry with iron overload, we identified an unacceptably high fraction, nearly half, who were not on chelation. Most of these patients were people with phenotypic homozygous SCD. We are systematically addressing this deficiency with educational tools through GRNDaD.Since GRNDaD sites are academic centers across the country which focus on the management of SCD, we speculate that the problem of undertreated iron overload nationally is probably both widespread and under-recognized. We anticipate that, as GRNDaD continues to add additional sites, it will evolve as a robust resource through which to highlight important opportunities for clinical quality improvement in the expanding young adult population with SCD. GRNDaD may be a model for identifying and addressing deficiencies in current clinical practices for management of SCD. [Display omitted] DisclosuresLanzkron:selexys: Research Funding; Ironwood: Research Funding; PCORI: Research Funding; HRSA: Research Funding; Pfizer: Research Funding; NHLBI: Research Funding; GBT: Research Funding; Prolong: Research Funding. Field:Incyte: Research Funding; Prolong: Research Funding; Ironwood: Consultancy, Research Funding. Desai:University of Pittsburgh: Research Funding; Selexy/Novartis: Research Funding; NIH: Research Funding; Ironwood: Other: Adjudication Committee; FDA: Research Funding; Pfizer: Research Funding. Little:PCORI: Research Funding; NHLBI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria; Doris Duke Charitable Foundations: Research Funding.