Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease

BACKGROUND AND OBJECTIVES: Adults with sickle cell disease (SCD) are at risk of decline in brain health and cognition, even without clinical stroke. SCD-related changes on MRI include brain atrophy and T2 fluid attenuated inversion recovery (FLAIR) white matter hyperintensity (WMH) growth. Hematopoietic stem cell transplant (HSCT) can be curative, but conditioning regimens risk new complications, particularly for adults with accumulated organ damage. We tested whether successful HSCT for adults with SCD was associated with reduced brain atrophy or WMH growth. METHODS: -transformed as a percentage of TICV. We tested whether HSCT success (persistent engraftment vs graft failure) or change in hemoglobin (Hb) (post-pre-HSCT) was associated with the rate of brain atrophy or WMH growth using mixed-effects linear regression. Random effects included scanner, participant intercept, and slope, while fixed effects included age and sex. RESULTS: = 0.50) and was associated with older age and baseline WMHs, but not treatment success. DISCUSSION: Successful HSCT was associated with preserved brain volume, but not WMH growth, another brain health biomarker. Whether these HSCT-related brain structural changes translate to cognitive preservation remains to be determined. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov NCT02140554 registered 2014-05-14, first enrollment February 2015; ClinicalTrials.gov NCT00061568; registered 2004-07-16, first enrollment July 2004; ClinicalTrials.gov NCT02105766; registered 2014-04-01, first enrollment April 2014; ClinicalTrials.gov NCT03077542; registered 2017-03-10, first enrollment April 2017; ClinicalTrials.gov NCT00977691; registered 2009-12-14, first enrollment December 2009. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that in adults with sickle cell disease, successful hematopoietic stem cell transplant is associated with slower declines in BPFs over a median period of 5 years, compared with patients with transplant failure.