TY - JOUR
T1 - Functional and Radiologic Assessment of the Brain after Reduced-Intensity Unrelated Donor Transplantation for Severe Sickle Cell Disease
T2 - Blood and Marrow Transplant Clinical Trials Network Study 0601
AU - King, Allison A.
AU - McKinstry, Robert C.
AU - Wu, Juan
AU - Eapen, Mary
AU - Abel, Regina
AU - Varughese, Taniya
AU - Kamani, Naynesh
AU - Shenoy, Shalini
N1 - Funding Information:
Financial disclosure: Support for this study was provided by Grant U10 HL069294 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute , as well as by funding from the National Marrow Donor Program, Sickle Cell Disease Clinical Research Network, and National Center on Minority Health and Health Disparities . The content is solely the responsibility of the authors and does not necessarily represent the official views of these agencies.
Publisher Copyright:
© 2019 American Society for Blood and Marrow Transplantation
PY - 2019/5
Y1 - 2019/5
N2 - Stroke and cognitive decline are hallmarks of sickle cell disease (SCD). The natural history of SCD predicts progressive loss of 1 IQ point per year attributable to disease-related pathology. Hematopoietic cell transplantation (HCT)is curative by reverting to donor-derived erythropoiesis, but evidence that HCT can positively influence disease-induced cognitive decline is lacking. The Sickle Cell Unrelated Transplant Trial prospectively evaluated cognition and brain magnetic resonance imaging (MRI)findings at 2 years after reduced-intensity conditioning followed by unrelated donor HCT. Thirteen study participants completed pre-HCT and post-HCT assessments of intelligence. The mean age of participants was 12.5 ± 3.3 years (range, 6.7 to 17.4 years). Eleven of the 13 recipients completed imaging studies at baseline and post-HCT. Seven had overt stroke pre-HCT, and 1 had an elevated transcranial Doppler velocity with abnormal MRI. The mean Full-Scale IQ was stable: 90.9 ± 13 at baseline and 91.2 ± 13 post-HCT. The mean Performance IQ was 89.9 ± 13 at baseline versus 90.9 ± 13 post-HCT, and mean Verbal IQ was 93.4 ± 13 at baseline versus 93.2 ± 13 post-HCT, respectively. Six recipients had stable MRI; 2 showed resolution of all areas of infarction. Three had additional infarcts post-HCT noted at the 2-year time point. This is the first report describing stabilization of IQ and central nervous system outcomes after unrelated donor HCT despite previous central nervous system morbidity and post-HCT posterior reversible encephalopathy syndrome. These preliminary results post-HCT suggest that HCT may stabilize the cognitive decline of SCD and should continue to be followed over the long term.
AB - Stroke and cognitive decline are hallmarks of sickle cell disease (SCD). The natural history of SCD predicts progressive loss of 1 IQ point per year attributable to disease-related pathology. Hematopoietic cell transplantation (HCT)is curative by reverting to donor-derived erythropoiesis, but evidence that HCT can positively influence disease-induced cognitive decline is lacking. The Sickle Cell Unrelated Transplant Trial prospectively evaluated cognition and brain magnetic resonance imaging (MRI)findings at 2 years after reduced-intensity conditioning followed by unrelated donor HCT. Thirteen study participants completed pre-HCT and post-HCT assessments of intelligence. The mean age of participants was 12.5 ± 3.3 years (range, 6.7 to 17.4 years). Eleven of the 13 recipients completed imaging studies at baseline and post-HCT. Seven had overt stroke pre-HCT, and 1 had an elevated transcranial Doppler velocity with abnormal MRI. The mean Full-Scale IQ was stable: 90.9 ± 13 at baseline and 91.2 ± 13 post-HCT. The mean Performance IQ was 89.9 ± 13 at baseline versus 90.9 ± 13 post-HCT, and mean Verbal IQ was 93.4 ± 13 at baseline versus 93.2 ± 13 post-HCT, respectively. Six recipients had stable MRI; 2 showed resolution of all areas of infarction. Three had additional infarcts post-HCT noted at the 2-year time point. This is the first report describing stabilization of IQ and central nervous system outcomes after unrelated donor HCT despite previous central nervous system morbidity and post-HCT posterior reversible encephalopathy syndrome. These preliminary results post-HCT suggest that HCT may stabilize the cognitive decline of SCD and should continue to be followed over the long term.
KW - Brain MRI
KW - Neurocognition
KW - Sickle cell disease
KW - Stem cell transplantation
UR - http://www.scopus.com/inward/record.url?scp=85061190072&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2019.01.008
DO - 10.1016/j.bbmt.2019.01.008
M3 - Article
C2 - 30639825
AN - SCOPUS:85061190072
SN - 1083-8791
VL - 25
SP - e174-e178
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 5
ER -