Hematopoietic Stem Cell Transplantation Stabilizes Cerebral Vasculopathy in High-Risk Pediatric Sickle Cell Disease Patients: Evidence From a Referral Transplant Center

Abstract

Background Severe sickle cell disease (SCD) can present with different vaso-occlusive manifestations with cerebral vasculopathy (CV) as one of the most serious complications. Hematopoietic stem cell transplant (HSCT) is the ultimate therapy for this complication. The aim of this study was to assess the outcome and impact of HSCT on severe SCD patients with CV complications. Methods Twenty-five consecutive transplants-naive pediatric SCD patients with CV complications underwent HSCT at our institution between 1993 and 2015, using bone marrow as stem cells source from fully match related donors were included. Neurologic evaluation was done both clinically and radiologically before transplantation and regularly following the HSCT. Results With a median follow-up of 52.2 ± 5.8 months, the cumulative probability of overall survival (OS) at 3 years was 92.0% and event-free survival (EFS) was 88%. Significant neurologic improvements were observed in most of the patients clinically. Different neurologic complications were assessed. The neurologic manifestations before and after HSCT were hemiparesis (11, 1), seizures (13, 8), focal neurologic deficit (4, 2), loss of conscious (2, 1) headache (6, 1), and psychological symptoms (5, 2). Post-HSCT radiological imaging was done in 15 patients, which showed stabilization of CV among all. Conclusions Allogeneic HSCT in patients with severe SCD presenting with CV complications including moyamoya vasculopathy showed favorable outcome with significant clinical neurologic improvement and stabilization of the disease. None of the patients with severe vasculopathy underwent neurological vascular by-pass surgery prior to 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 8,18–21,23,25–29,31,35–42,44–47 . 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.…”

“…Numerous studies investigated the occurrence of neurological events and found no new ischemic infarcts or stable MRI findings, following HSCT in successfully engrafted patients with SCD 8,18,19,21,23,25,27–29,38,40,42,44–46 . Only two studies reported new overt infarcts post‐HSCT in a minority (<5%) of the investigated patients, most likely because these studies included formal neurological evaluation and MRI of the brain with central adjudicaiton 20,35 .…”

Cerebral hemodynamic changes after haploidentical hematopoietic stem cell transplant in adults with sickle cell disease

“… 3 , 4 , 5 , 6 Currently, the mainstays of disease-modifying therapy include hydroxyurea and regular blood transfusions, although unfortunately, new cerebral infarcts occur in some patients despite interventions. 7 Curative therapy such as hematopoietic stem cell transplant (HSCT) using haploidentical bone marrow transplant (haplo-BMT) is appealing because haplo-BMT should improve cerebral hemodynamics, reduce the risk of new infarcts, 8 , 9 and prevent progressive cerebral vasculopathy 10 with better availability than standard BMT. 11 However, other than a case series of 4 adults with improved cerebral hemodynamics after haplo-BMT, 12 this has not yet been confirmed in adults with SCD.…”