Haploidentical bone marrow transplantation improves cerebral hemodynamics in adults with sickle cell disease

Jordan, Lori C.; Juttukonda, Meher R.; Kassim, Adetola A.; DeBaun, Michael R.; Davis, L. Taylor; Pruthi, Sumit; Patel, Niral; Lee, Chelsea A.; Waddle, Spencer; Donahue, Manus J.

doi:10.1002/ajh.25455

Cited by 16 publications

(11 citation statements)

References 10 publications

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“…22,36 However, the observed increase in OEF values after HSCT is in contrast with prior studies that reported a decrease in OEF after HSCT, which could be attributed to differences in the methodologies employed. 22,36 The In SCD patients, reduced hemoglobin levels lead to increased CBF due to the body's compensation for reduced oxygen-carrying capacity. This increase can lower the vasodilatory reserve capacity due to chronic vessel dilation at rest and compromises oxygen extraction through functional shunting.…”

Section: Discussioncontrasting

confidence: 97%

“…The normalization of CBF values following HSCT is in agreement with previous studies in transplanted children with SCD and a small study of four adult SCD patients 22,23,36 . Furthermore, the OEF values observed in this work align with two previous studies reporting that after HSCT, OEF values in SCD patients reached values observed in healthy controls 22,36 .…”

Section: Discussionsupporting

confidence: 92%

“…22,23,36 Furthermore, the OEF values observed in this work align with two previous studies reporting that after HSCT, OEF values in SCD patients reached values observed in healthy controls. 22,36 However, the observed increase in OEF values after HSCT is in contrast with prior studies that reported a decrease in OEF after HSCT, which could be attributed to differences in the methodologies employed. 22,36 The In SCD patients, reduced hemoglobin levels lead to increased CBF due to the body's compensation for reduced oxygen-carrying capacity.…”

Section: Discussionsupporting

confidence: 91%

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Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation

Afzali‐Hashemi,

Dovern,

Baas

et al. 2023

American J Hematol

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Sickle cell disease (SCD) is characterized by chronic hemolytic anemia associated with impaired cerebral hemodynamics and oxygen metabolism. Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for patients with SCD. Whereas normalization of hemoglobin levels and hemolysis markers has been reported after HSCT, its effects on cerebral perfusion and oxygenation in adult SCD patients remain largely unexplored. This study investigated the effects of HSCT on cerebral blood flow (CBF), oxygen delivery, cerebrovascular reserve (CVR), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in 17 adult SCD patients (mean age: 25.0 ± 8.0, 6 females) before and after HSCT and 10 healthy ethnicity‐matched controls (mean age: 28.0 ± 8.8, 6 females) using MRI. For the CVR assessment, perfusion scans were performed before and after acetazolamide as a vasodilatory stimulus. Following HSCT, gray and white matter (GM and WM) CBF decreased (p < .01), while GM and WM CVR increased (p < .01) compared with the baseline measures. OEF and CMRO2 also increased towards levels in healthy controls (p < .01). The normalization of cerebral perfusion and oxygen metabolism corresponded with a significant increase in hemoglobin levels and decreases in reticulocytes, total bilirubin, and LDH as markers of hemolysis (p < .01). This study shows that HSCT results in the normalization of cerebral perfusion and oxygen metabolism, even in adult patients with SCD. Future follow‐up MRI scans will determine whether the observed normalization of cerebral hemodynamics and oxygen metabolism prevents new silent cerebral infarcts.

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Section: Discussioncontrasting

confidence: 97%

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

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Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation

Afzali‐Hashemi,

Dovern,

Baas

et al. 2023

American J Hematol

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“…Post-transfusion reductions in OEF (191, 255) and increases in CVR (162) have also been reported. Similar hemodynamic changes in global OEF and CBF have also been observed following bone marrow transplantation (287), which is the only curative treatment option currently available for SCD. Taken together, these findings provide proof of principle that normalization of CaO 2 and hyperemia, along with restoration of vascular reserves, may contribute to the efficacy of transfusion in reducing risk of overt stroke.…”

Section: A Systems-biology Frameworkmentioning

confidence: 60%

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

et al. 2019

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It is well-established that patients with sickle cell disease (SCD) are at substantial risk of neurological complications, including overt and silent stroke, microstructural injury, and cognitive difficulties. Yet the underlying mechanisms remain poorly understood, partly because findings have largely been considered in isolation. Here, we review mechanistic pathways for which there is accumulating evidence and propose an integrative systems-biology framework for understanding neurological risk. Drawing upon work from other vascular beds in SCD, as well as the wider stroke literature, we propose that macro-circulatory hyper-perfusion, regions of relative micro-circulatory hypo-perfusion, and an exhaustion of cerebral reserve mechanisms, together lead to a state of cerebral vascular instability. We suggest that in this state, tissue oxygen supply is fragile and easily perturbed by changes in clinical condition, with the potential for stroke and/or microstructural injury if metabolic demand exceeds tissue oxygenation. This framework brings together recent developments in the field, highlights outstanding questions, and offers a first step toward a linking pathophysiological explanation of neurological risk that may help inform future screening and treatment strategies.

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“…Elevated global CBF may be both a response to and a risk factor for cerebral hypoxia [ 116 ]. Studies have shown a reduction of global CBF following treatment with hydroxyurea [ 116 ], transfusion – more in children than adults [ 117 ], and bone marrow transplantation [ 118 , 119 ] Strouse et al . [ 120 ] found a strong inverse correlation between global CBF and both full-scale IQ and performance IQ.…”

Section: Quantitative Imaging In Steady-state Settingsmentioning

confidence: 99%

MRI detection of brain abnormality in sickle cell disease

Stotesbury

Kawadler

Saunders

et al. 2021

Expert Review of Hematology

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Introduction: Over the past decades, neuroimaging studies have clarified that a significant proportion of patients with sickle cell disease (SCD) have functionally significant brain abnormalities. Clinically, structural magnetic resonance imaging (MRI) sequences (T2, FLAIR, diffusion-weighted imaging) have been used by radiologists to diagnose chronic and acute cerebral infarction (both overt and clinically silent), while magnetic resonance angiography and venography have been used to diagnose arteriopathy and venous thrombosis. In research settings, imaging scientists are increasingly applying quantitative techniques to shine further light on underlying mechanisms. Areas covered: From a June 2020 PubMed search of 'magnetic' or 'MRI' and 'sickle' over the previous 5 years, we selected manuscripts on T1-based morphometric analysis, diffusion tensor imaging, arterial spin labeling, T2-oximetry, quantitative susceptibility, and connectivity. Expert Opinion: Quantitative MRI techniques are identifying structural and hemodynamic biomarkers associated with risk of neurological and neurocognitive complications. A growing body of evidence suggests that these biomarkers are sensitive to change with treatments, such as blood transfusion and hydroxyurea, indicating that they may hold promise as endpoints in future randomized clinical trials of novel approaches including hemoglobin F upregulation, reduction of polymerization, and gene therapy. With further validation, such techniques may eventually also improve neurological and neurocognitive risk stratification in this vulnerable population.

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Haploidentical bone marrow transplantation improves cerebral hemodynamics in adults with sickle cell disease

Cited by 16 publications

References 10 publications

Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation

Cerebral hemodynamics and oxygenation in adult patients with sickle cell disease after stem cell transplantation

Vascular Instability and Neurological Morbidity in Sickle Cell Disease: An Integrative Framework

MRI detection of brain abnormality in sickle cell disease

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