Transcranial Doppler sonography and the effect of haematopoietic stem cell transplantation in sickle cell disease

Abstract

Background Sickle cell disease (SCD) is one of the most prevalent monogenetic diseases worldwide and one of the most serious complications is stroke. Transcranial Doppler (TCD) demonstrated to be highly predictive for an imminent stroke by measuring blood flow velocities in the basal cerebral arteries. Currently, the only curative therapy for SCD is hematopoietic stem cell transplantation (HSCT). The aim of this study is to verify the correlation between blood flow velocities and stroke including the effect of HSCT. Methods In our retrospective single-center study a total of 26 sickle cell patients (HbSS, HbSß+-thalassemia, HbSSα-thalassemia minima, HbSSα-thalassemia minor and HbSC) were analyzed between 2010 and 2016. The highest time averaged maximum mean blood flow velocity (TAMMV) measured was documented and evaluated with respect to SCD genotype and effect of HSCT. Acute and symptomatic as well as silent strokes were recorded as separate parameters. Results In our study, ten patients had normal blood flow velocities before HSCT (six HbSS and four HbSß+-thalassemia patients) and 13 patients presented with abnormal TCD (eight HbSS, three HbSSα-thalassemia minima, one HbSSα-thalassemia minor and one HbSC). Thirteen of 26 study participants (ten HbSS and three HbSß+-thalassemia patients) received HSCT. In two patients, TAMMV in basal cerebral arteries remained “normal”, in one they remained conditional and in one TAMMV was reduced to normal. Four of 26 study participants (15.4%), including all patients with HbSS genotype, presented with a stroke, but none had “abnormal” TAMMV with TCD performed after the onset of stroke in each case. At the time we performed the TCD, the patients had already suffered the stroke. Conclusion In our study, none of the patients with stroke displayed abnormal blood flow velocities in TCD. Yet, HSCT at this stage of the disease still had a positive effect on TAMMV. Further studies are needed whether this effect converts into reduced stroke risk at all or only selected SCD patients undergoing HSCT.

Effect of allogeneic hematopoietic stem cell transplantation on sickle cell disease‐related organ complications: A systematic review and meta‐analysis

“…After reviewing the full‐text articles, another five studies were excluded based on study design (two because of missing outcome measure, one because of limited follow‐up, one was a literature review, and one because of different patient population). Finally, 34 studies were eligible for inclusion 8,18–50 . All 34 studies were used for the qualitative synthesis, of which 17 studies were also used in the meta‐analyses comparing organ function before and after HSCT.…”

“…Twenty-four studies were identified that investigated either the presence of (silent) cerebral infarcts, vasculopathy, or cerebral hemodynamics before and after HSCT. 8,[18][19][20][21]23,[25][26][27][28][29]31,[35][36][37][38][39][40][41][42][44][45][46][47] Except for whole-brain cerebral blood flow and peak transcranial Doppler velocity (both low "Clinical Diversity in Meta-analyses" score 9), the reported outcome measures and patient inclusion criteria were too heterogenous to be pooled in a meta-analysis. A summary of the study characteristics evaluating cerebral function parameters and cerebral damage and their main findings is presented in Tables S7 and S8.…”

“…39 Transcranial Doppler velocities of children before and after HSCT were reported in ten studies. 20,23,29,31,[35][36][37]41,42,46 Three of these studies reported time-averaged maximum transcranial Doppler velocities before and after HSCT as a continuous outcome and were included in the meta-analysis. 23,41,42 The decrease in transcranial Doppler velocity did not reach statistical significance (SMD-2.50, p = 0.13), probably due to the high statistical heterogeneity (Figure 2, Figure S5).…”

Managing the Cerebrovascular Complications of Sickle Cell Disease: Current Perspectives

“…Cerebrovascular benefits are established by multiple studies, with improved stenosis scores, improved TCDs, and reduction in strokes post-transplant. 113 , 114 Given the availability of effective disease-modifying therapy, however, the risks of HSCT must be carefully considered. 115–117…”

“…Cerebrovascular benefits are established by multiple studies, with improved stenosis scores, improved TCDs, and reduction in strokes post-transplant. 113,114 Given the availability of effective disease-modifying therapy, however, the risks of HSCT must be carefully considered. [115][116][117] Complications of HSCT include effects of pre-HSCT conditioning therapy, infection, graft rejection, and acute or chronic graft-versus-host disease (GVHD).…”