▪ IntroductionThe integration of prognostic information into the clinical care of adults with sickle cell disease (SCD) assumes greater importance as more intensive therapeutic strategies are being developed, including hematopoietic stem cell transplantation (HSCT). In addition, more high-risk alternate donor options predominate in SCD, since allogeneic HSCT candidates seldom have matched sibling donors (MSD). We wanted to integrate individual clinical risk factors for death, such as white blood cell count (Platt, NEJM, 1994) or Tricuspid Regurgitant Jet Velocity (TRV), (Gladwin, NEJM, 2004) into eligibility criteria for HSCT. MethodsBaseline demographics, laboratory values, high-risk TRV (greater than 3.0 m/s), and 2-year mortality data on adults with SCD, available from the multi-centered Walk-PHaSST study (n=468 HbSS, 19 deaths), were used to estimate one- and two-variable positive predictive values (PPVs) for short-term mortality (Figure 1A). Using these data, we suggest the basis for a graded (‘stop light') HSCT eligibility schema in which patients with morbid disease and <10% 2-year mortality (green light, ‘low risk' disease) could be considered for standard-risk HSCT (e.g. reduced-intensity MSD) (Figure 1B). 10-15% mortality (yellow light, ‘moderate risk') or highly morbid disease could be considered for alternate donor transplants in which there is published experience in adults (e.g. reduced intensity haploidentical, Bolanos-Meade, Blood 2012). >15% mortality (red light, ‘high risk' disease) could be considered for high-risk alternate donor transplants (without published experience in adults, e.g. cord blood). We then applied this method for estimating HSCT eligibility to HbSS adults followed at University Hospitals Case Medical Center in Cleveland, Ohio (n=122), and contrasted this with criteria based on published recommendations (Hseih, NEJM, 2009), (STRIDE trial: http://clinicaltrials.gov/show/NCT01565616). ResultsWe developed a simple mortality-based prognostic scale with which to estimate SCD severity prior to referring for HSCT. In Walk-PHASST, multiple clinical variables contributed to high risk SCD (red boxes, Figure 1A). The Cleveland population is young (median age 28 years). Nonetheless, 23% (28 of 122) were high risk (red) patients, and 52% (64 of 122) were moderate risk (yellow) or had highly morbid disease. 12% (15 of 122) had low risk (green) SCD and morbid disease, based on our proposed ‘stop light' eligibility schema. Published eligibility criteria, which do not stratify based on SCD prognosis, identify 75-86% of adults in our center as having ≥1 indications for HSCT. [Display omitted] ConclusionsAlthough estimation of risk from transplant is evolving, we believe the proposed ‘stop light' graded eligibility may aid in the selection of appropriate patients and in risk-benefit counseling. We recognize the limitations of a scale based on a modest number of deaths. Nonetheless our simple mortality based prognostic scale is a tool with which to approach the integration of disease severity and HSCT risk in SCD.Yellow: Patients at moderate risk for 2-year (10-15%) mortality (yellow boxes, Figure 1A) or with highly morbid disease (>5 hospitalizations per year, h/o CVA, h/o silent infarct, estimated GFR <90 mL/min, macroalbuminuria, ≥2 ACS within 5 years, or sickle hepatopathy) are eligible for alternate donors with which there is published experience in adults (e.g. haploidentical as well as MSD).Green: Patients with 2-year mortality (<10%) but with morbid disease (>2 hospitalizations per year for two or more years, or acute chest within the past five years) are eligible for standard-risk HSCT (MSD only). Disclosures:No relevant conflicts of interest to declare.