TY - JOUR
T1 - Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia
AU - Fields, Melanie E.
AU - Guilliams, Kristin P.
AU - Ragan, Dustin
AU - Binkley, Michael M.
AU - Mirro, Amy
AU - Fellah, Slim
AU - Hulbert, Monica L.
AU - Blinder, Morey
AU - Eldeniz, Cihat
AU - Vo, Katie
AU - Shimony, Joshua S.
AU - Chen, Yasheng
AU - McKinstry, Robert C.
AU - An, Hongyu
AU - Lee, Jin Moo
AU - Ford, Andria L.
N1 - Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019/5/30
Y1 - 2019/5/30
N2 - Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P 5. 148). However, whole-brain OEF was significantly different (P <. 001): participants with out disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P 5. 025 and P 5. 034 respectively), but higher compared with the CTT cohort (P 5. 018 and P 5. 029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.
AB - Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P 5. 148). However, whole-brain OEF was significantly different (P <. 001): participants with out disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P 5. 025 and P 5. 034 respectively), but higher compared with the CTT cohort (P 5. 018 and P 5. 029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.
UR - http://www.scopus.com/inward/record.url?scp=85067242608&partnerID=8YFLogxK
U2 - 10.1182/blood-2018-09-876318
DO - 10.1182/blood-2018-09-876318
M3 - Article
C2 - 30858231
AN - SCOPUS:85067242608
SN - 0006-4971
VL - 133
SP - 2436
EP - 2444
JO - Blood
JF - Blood
IS - 22
ER -