TY  - CHAP
M1  - Book, Section
TI  - Hematopoietic Stem Cell Transplantation in Sickle Cell Disease
A1  - Leonard, Alexis
A1  - Tisdale, John F.
A1  - Krishnamurti, Lakshmanan
A1  - Walters, Mark C.
A2  - Gladwin, Mark T.
A2  - Kato, Gregory J.
A2  - Novelli, Enrico M.
PY  - 2021
T2  - Sickle Cell Disease
AB  - Sickle  cell  disease  (SCD)  is  the  most  common  inherited  hemoglobinopathy  worldwide  and  is  associated  with  substantial  morbidity,  high  health  care  utilization,  and  premature  mortality.  Although  hydroxyurea  (HU),  chronic  blood  transfusions,  and  L-glutamine  decrease  SCD-associated  complications,  they  do  not  eliminate  them  and  thus  need  to  be  continued  indefinitely.  Allogeneic  hematopoietic  stem  cell  transplantation  (HSCT)  is  the  only  currently  available  curative  option  for  patients  with  SCD.  Disease-free  survival  (DFS)  in  children  and  young  adults  with  SCD  is  >95%  after  a  myeloablative  regimen  using  a  human  leukocyte  antigen  (HLA)-matched  sibling  donor.  Mixed  donor  chimerism  with  ≥20%  donor  myeloid  cells  is  associated  with  predominant  donor-derived  erythropoiesis  due  to  normal  donor  red  blood  cell  (RBC)  survival  compared  to  the  ineffective  erythropoiesis  of  SCD.  Thus,  reduced-intensity  conditioning  (RIC)  and  nonmyeloablative  conditioning  appear  efficacious  and  safe  for  adults  with  an  HLA-identical  sibling  donor  who  may  otherwise  be  unable  to  tolerate  myeloablative  conditioning.  HSCT  is  still  largely  underused  in  part  due  to  the  lack  of  available  matched  donors  for  patients  with  SCD  and  concerns  about  morbidity  and  mortality  from  transplantation  conditioning,  graft-versus-host  disease  (GVHD),  and  graft  rejection.  Approaches  to  improve  the  safety,  efficacy,  and  applicability  of  HSCT  for  SCD  that  are  currently  being  tested  in  clinical  trials  include  novel  low-intensity  conditioning,  novel  graft  manipulation  techniques  to  reduce  the  risk  of  GVHD,  novel  strategies  for  GVHD  prophylaxis,  and  the  use  of  alternate  sources  of  hematopoietic  progenitor  cells  including  HLA-haploidentical  donors  (matched  at  50%  of  HLA  alleles),  umbilical  cord  blood  (UCB),  and  matched  unrelated  donors.  Simultaneously,  significant  advances  in  gene  therapy  suggest  that  a  universal  cure(s)  for  SCD  might  soon  be  available  that  eliminates  major  limitations  of  allogeneic  transplantation,  and  this  is  being  investigated  in  multiple  clinical  trials.  
SN  - 
PB  - McGraw-Hill Education
CY  - New York, NY
Y2  - 2024/04/16
UR  - hemonc.mhmedical.com/content.aspx?aid=1179345234
ER  -