TY - JOUR
T1 - Umbilical cord blood as a hematopoietic stem cell source in transplantation for pediatric sickle cell disease
T2 - current challenges and strategies
AU - Malhotra, Megha
AU - Shenoy, Shalini
N1 - Funding Information:
This work was supported by the Children's Discovery Institute at Washington University and the St. Louis Children's Hospital Foundation.
Funding Information:
This work was supported by the Children’s Discovery Institute at Washington University and the St. Louis Children’s Hospital Foundation .
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/10
Y1 - 2022/10
N2 - Allogeneic hematopoietic stem cell transplant (HSCT) is the only established cure for sickle cell disease (SCD), a hemolytic disorder that arises due to a point mutation in the hemoglobin A gene. The result is an abnormal sickle hemoglobin (HbS) replacing hemoglobin A. Of the spectrum of sickle hemoglobinoapthies, homozygous (HbSS) and HbSβ0 thalassemia manifest severe forms of disease characterized by chronic endothelial injury/vasculopathy, ischemic pain, and vital organ damage that commence in childhood and escalate with age resulting in impaired quality of life, increased healthcare burden, and early mortality. HSCT has demonstrated durable disease control and regression of symptoms. Human leukocyte antigen (HLA) matched sibling donor (MSD) transplantation can achieve disease-free survival of > 90%. However, < 18% of SCD patients in the United States have a MSD. Familial mismatched and unrelated donors from registries provide alternate stem cell sources. Umbilical cord blood (UCB) from family or cord blood banks expand donor sources and are attractive due to donor-independent ease of use and availability. These naïve cells tolerate greater degrees of HLA-mismatch. The primary challenge with UCB is optimizing cell dose toward successful engraftment and timely immune reconstitution while minimizing graft-versus-host disease (GVHD). This review summarizes evidence that UCB remains a promising stem cell source where modern methods of graft expansion, conditioning, GVHD prophylaxis, and infection control can overcome these challenges and retain the value of this intervention.
AB - Allogeneic hematopoietic stem cell transplant (HSCT) is the only established cure for sickle cell disease (SCD), a hemolytic disorder that arises due to a point mutation in the hemoglobin A gene. The result is an abnormal sickle hemoglobin (HbS) replacing hemoglobin A. Of the spectrum of sickle hemoglobinoapthies, homozygous (HbSS) and HbSβ0 thalassemia manifest severe forms of disease characterized by chronic endothelial injury/vasculopathy, ischemic pain, and vital organ damage that commence in childhood and escalate with age resulting in impaired quality of life, increased healthcare burden, and early mortality. HSCT has demonstrated durable disease control and regression of symptoms. Human leukocyte antigen (HLA) matched sibling donor (MSD) transplantation can achieve disease-free survival of > 90%. However, < 18% of SCD patients in the United States have a MSD. Familial mismatched and unrelated donors from registries provide alternate stem cell sources. Umbilical cord blood (UCB) from family or cord blood banks expand donor sources and are attractive due to donor-independent ease of use and availability. These naïve cells tolerate greater degrees of HLA-mismatch. The primary challenge with UCB is optimizing cell dose toward successful engraftment and timely immune reconstitution while minimizing graft-versus-host disease (GVHD). This review summarizes evidence that UCB remains a promising stem cell source where modern methods of graft expansion, conditioning, GVHD prophylaxis, and infection control can overcome these challenges and retain the value of this intervention.
KW - Allogeneic hematopoietic stem cell transplant
KW - Engraftment
KW - Graft-versus-host disease
KW - Immune reconstitution
KW - Sickle cell disease
KW - Umbilical cord blood transplant
UR - http://www.scopus.com/inward/record.url?scp=85137723083&partnerID=8YFLogxK
U2 - 10.1016/j.transci.2022.103554
DO - 10.1016/j.transci.2022.103554
M3 - Article
C2 - 36096996
AN - SCOPUS:85137723083
SN - 1473-0502
VL - 61
JO - Transfusion and Apheresis Science
JF - Transfusion and Apheresis Science
IS - 5
M1 - 103554
ER -