Bone marrow transplantation in a young child with sickle cell anemia

Abstract

Bone marrow transplantation (BMT) is the only curative therapy available for hemoglobinopathies. BMT was performed on a young child with sickle cell anemia (SCA) after approximately 9 months of transfusion therapy following her initial stroke. The patient received a matched sibling donor (sickle trait) BMT. The conditioning regimen consisted of busulfan 4 mg/kg/day x 4, cyclophosphamide 50 mg/kg/day x 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6 months. There were no significant complications during BMT. Engraftment occurred on day +17 and the patient was transfusion independent since day +45. Pre-BMT cerebral arteriography showed multiple stenotic cerebral vessels and a moya-moya pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately 170 days after BMT the patient experienced episodes of transient left-sided weakness and speech problems. Neuroimaging revealed progression of large vessel pathology by angiography despite significant improvement in cortical perfusion (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk viscosity. It is possible that progression of large vessel pathology and return of clinical symptoms in the face of normal rheologic parameters may be due to worsening of the already damaged cerebral vessels by the BMT conditioning regimen. Further evaluations of patients with SCA undergoing BMT after a stroke are needed to answer this question.

Guidelines and Recommendations for Perfusion Imaging in Cerebral Ischemia

“…70 Perfusion imaging might be used to determine when a patient with moyamoya disease or syndrome should undergo a procedure to augment flow. 82,83 Conceivably, such tests could be used to select those patients for carotid endarterectomy or angioplasty and stenting who have multiple vascular stenoses and occlusions but who do not now qualify for such procedures by demonstrating focal neurological symptoms and a 70% or greater stenosis. However, this will take large, well-planned studies utilizing control groups to compare natural history data with postprocedural outcomes.…”

Hematopoietic Stem Cell Transplantation for Sickle Cell Disease: Current Practice and Emerging Trends

“…12 However, on cerebral imaging, new MRA/MRI changes were noted after HSCT in patients with previous MRI abnormalities (lacunae/infarcts); stroke has also been reported after HSCT. 39,40 If underlying vasculopathy is to blame, additional stressors such as toxicities from the conditioning, cytokine storm and engraftment syndrome, hemodynamic changes of HSCT, and GVHD-related complications could be a negative influence. The age and eligibility for transplantation, conditioning strategy, management of SCD patients after HSCT, and tailoring transplantation strategies based on donor availability and recipient status are the focus of newer transplantation trials and worthy of investigation.…”

Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease

“…The other patient had evidence of progressive CNS vasculopathy on MRA at 30 months after UPBCT, but because of the long interval between pretransplant and follow-up MRA studies it is not known whether those changes occurred before or after UPCBT. Progression of stenosis in large cerebral arteries has occurred in some children with SCD who received BMTs from HLA-matched sibs; 45,46 [and F Bernaudin, personal communication], but its etiology remains unclear.…”