Session: 904. Outcomes Research: Hemoglobinopathies: Poster III
Hematology Disease Topics & Pathways:
Research, Sickle Cell Disease, Adult, Epidemiology, Clinical Research, Hemoglobinopathies, Pediatric, Diseases, Study Population, Human
Methods: We selected patients with SCA, ≥5 years of age, on hydroxyurea therapy enrolled in the Sickle Cell Clinical Research and Intervention Program (SCCRIP, NCT02098863) who had a documented HbF level of >20% for at least 3 consecutive years. Hematological parameters and sickle cell clinical outcomes data (healthcare utilization for VOC, urine microalbumin creatinine ratio, transcranial doppler velocity, tricuspid regurgitant jet velocity and PedsQL-SCD (Pain and Hurt subscale) during this period of persistently high HbF levels, were abstracted from the SCCRIP database. We defined high VOC event burden as a median healthcare (emergency and/or hospitalization) utilization rate for VOC of ≥0.5 events/patient-year. The propensity score method was used to select individuals with low VOC burden (<0.5 events/patient-year) to match for age and sex with those with high VOC burden, using a 1: 3 matching frequencies. Two-sample t-test or Wilcoxon rank sum was used to compare continuous data, and Fisher’s exact or Chi-square test was used to compare categorical variables between the low and high VOC burden groups.
Results: One hundred forty-two participants (median age 9 years, IQR 9-16) with SCA met the criteria for sustained HbF response to hydroxyurea. Twenty-nine participants had a high VOC burden. Participants in the high VOC burden group compared to the low VOC burden (n=113) group, were older (median age 15 vs 13 years, p = 0.053), had lower PedsQL-SCD pain-hurt scores reflecting worse pain control (61, range 47-83 vs 83, range 67-96, p = 0.03) and worsening early diastolic mitral velocity at the septal annulus (septal e’), an echocardiographic surrogate for left ventricular relaxation and used to assess diastolic function (13.5 vs 15 cm/sec, p=0.06) which was trending towards significance. After matching for age and sex, 87 individuals were noted to have low VOC burden. Only PedsQL-SCD pain hurt scores were lower in the high VOC burden group compared to low VOC burden group (61, range 47-83 vs 84, range 64-97, p =0.041), with no other evidence of organ injury.
Conclusion: In this study, we highlight an SCA population with a high VOC burden and impaired health-related quality of life despite having persistently high HbF levels (>20%). However, we did not find other markers for end-organ injury (microalbuminuria, elevated TRV and TCD velocity) in those with high VOC burden. The pathophysiology of VOC in SCD is complex and multifactorial. Our findings suggest that high HbF might not be sufficient to ameliorate VOC in some individuals, and, additional therapies interrupting sickle polymerization, or downstream pathways might be needed. While our study is limited by the small sample size and missing data on clinical outcomes, these findings underscore the need for further investigation in a larger cohort.
Disclosures: Rai: Global Blood Therapeutics: Consultancy. Jesudas: Merck: Consultancy, Honoraria. Takemoto: Novo Nordisk: Research Funding; Pfizer: Research Funding; Novartis: Other: DSMB; Merck: Consultancy, Honoraria.
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