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. 2023 Jan 26;141(4):335-344.
doi: 10.1182/blood.2022016618.

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease

Monica L Hulbert  1 , Melanie E Fields  1   2 , Kristin P Guilliams  1   2   3 , Priyesha Bijlani  4 , Shalini Shenoy  1 , Slim Fellah  3 , Alison S Towerman  1 , Michael M Binkley  5 , Robert C McKinstry  3 , Joshua S Shimony  3 , Yasheng Chen  3 , Cihat Eldeniz  3 , Dustin K Ragan  6 , Katie Vo  3 , Hongyu An  3 , Jin-Moo Lee  2   3 , Andria L Ford  2   3
Affiliations

Normalization of cerebral hemodynamics after hematopoietic stem cell transplant in children with sickle cell disease

Monica L Hulbert et al. Blood. .

Abstract

Children with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (-19.4 mL/100 g/min) and OEF (-8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, -0.9 mL/100 g/min; P = .024; OEF, -3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population.

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Conflict of interest statement

Conflict-of-interest disclosure: M.L.H. has spouse employed at Pfizer Inc, is a consultant for bluebird bio and for Global Blood Therapeutics, and has received research funding from Global Blood Therapeutics and Forma Therapeutics. M.E.F. owns equity at Proclara Biociences, participated in a scientific advisory board with compensation at bluebird bio, and is a consultant for Global Blood Therapeutics. S.S. is a consultant for Aruvant Sciences and participated in scientific advisory boards with compensation at Bristol Myers Squibb, Graphite Bio, and Janssen Pharmaceuticals. M.B.B. is employed at Open Cell Technologies Inc. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Representative maps from participant F before HSCT (age 11 years) and after HSCT (age 12 years). CBF and OEF were elevated at baseline, and were similar to those of a sex–matched, 13-year-old control participant, 1 year after curative HSCT. sib, sibling.
Figure 2.
Figure 2.
Hb and Hct are inversely correlated with OEF before and after HSCT. Each HSCT recipient’s data points are shown with an arrow oriented from before HSCT to after HSCT. The 95% CI (shaded) and regression line (red) are derived from the OEF and CBF measurements of the CRTT cohort. (A) Correlation between 1/Hb and OEF before HSCT (Spearman's ρ, 0.818; P = .004) and after HSCT (Spearman’s ρ, 0.842; P = .002). (B) Correlation between 1/Hct and OEF before HSCT (Spearman’s ρ, 0.869; P = .0011) and after HSCT (Spearman’s ρ, 0.952; P < .0001). (C) Correlation between 1/Hb and CBF before HSCT (Spearman’s ρ, 0.479; P = .162) and after HSCT (Spearman’s ρ, 0.115; P = .751). (D) Correlation between 1/Hct and CBF before HSCT (P = .162) or after HSCT (P = .726).
Figure 3.
Figure 3.
Comparison of CBF and OEF between CRTT and HSCT SCD participants and children in the control group. (A) CBF is elevated before HSCT, similar to CRTT participants, and declines to control values after HSCT. (B) OEF is elevated before HSCT, similar to CRTT participants, and declines to control values after HSCT. This change is greater than the OEF improvement seen after a scheduled transfusion among CRTT recipients. NS, not significant; WB, whole brain.
See this image and copyright information in PMC

Comment in

  • Anemia and brain hypoxia.
    Wood JC. Wood JC. Blood. 2023 Jan 26;141(4):327-328. doi: 10.1182/blood.2022018229. Blood. 2023. PMID: 36701169 Free PMC article. No abstract available.

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