RT Book, Section
A1 Olson, Amanda
A1 Ramdial, Jeremy
A1 Greenbaum, Uri
A1 Lin, Paul
A1 Rezvani, Katayoun
A1 Kebriaei, Partow
A2 Kantarjian, Hagop M.
A2 Wolff, Robert A.
A2 Rieber, Alyssa G.
SR Print(0)
ID 1190834149
T1 Cellular Therapy in Allogeneic Hematopoietic Cell Transplantation
T2 The MD Anderson Manual of Medical Oncology, 4e
YR 2022
FD 2022
PB McGraw Hill Education
PP New York, NY
SN 9781260467642
LK hemonc.mhmedical.com/content.aspx?aid=1190834149
RD 2024/04/19
AB KEY  CONCEPTSThe  efficacy  of  allogeneic  hematopoietic  cell  transplantation  (HCT)  is  based  on  the  graft-versus-tumor  effect,  by  which  the  donor  immune  system  achieves  immunologic  control  of  the  tumor  via  the  human  leukocyte  antigen  (HLA)  system.Three  key  barriers  to  successful  HCT  are  relapse  caused  by  failure  of  immunologic  control  of  the  underlying  disease,  graft-versus-host  disease  (GVHD),  and  infectious  complications,  and  studies  are  underway  to  improve  on  these  complications.Strategies  to  mitigate  relapse  include  using  prophylactic  donor  lymphocyte  infusions,  chimeric  antigen  receptor  modified  T-cells  derived  typically  from  the  patient,  and  natural  killer  (NK)  T-cells.In  contrast  to  B  and  T  lymphocytes,  NK  T-cells  do  not  express  rearranged,  antigen-specific  receptors  and  as  a  consequence  have  a  low  risk  for  GVHD,  allowing  the  use  of  allogeneic  NK  cells.  An  allogeneic  product  is  advantageous  because  it  is  readily  available  and  furthermore  uses  healthy  immune  cells  for  product  production.The  pathogenesis  of  GVHD  is  complex  and  includes  the  differentiation  of  naïve  donor  T-cells  into  effector  cells  that  attack  host  tissues.  Increasing  numbers  of  HLA  misma  tches  are  associated  with  higher  incidence  of  GVHD  and  transplant-related  mortality.  Grades  II  to  IV  acute  GVHD  occur  in  25%  to  60%  of  cases  with  matched  related  donors  and  45%  to  70%  of  cases  with  matched  unrelated  donors.  Recent  improvements  in  GVHD  include  the  approval  of  ruxolitinib  for  steroid-refractory  acute  GVHD  and  the  use  of  posttransplant  cyclophosphamide  to  decrease  the  incidence  of  GVHD.Viral  infection  is  a  major  cause  of  death  after  HCT,  resulting  from  cellular  and  humoral  immune  deficiency.  Viral  infections  of  particular  relevance  after  HCT  are  cytomegalovirus,  Epstein-Barr  virus,  the  polyoma  viruses  BK  and  JC,  adenovirus,  and  human  herpesvirus  6.  Pharmacotherapy  for  these  infections  has  limited  efficacy.  Viral-specific  T-cells  directed  against  these  infections  is  feasible  to  generate  and  effective.