PMID- 21684345
OWN - NLM
STAT- MEDLINE
DCOM- 20120531
LR  - 20211020
IS  - 1523-6536 (Electronic)
IS  - 1083-8791 (Print)
IS  - 1083-8791 (Linking)
VI  - 17
IP  - 12
DP  - 2011 Dec
TI  - Immune reconstitution in recipients of photodepleted HLA-identical sibling donor 
      stem cell transplantations: T cell subset frequencies predict outcome.
PG  - 1846-54
LID - 10.1016/j.bbmt.2011.05.017 [doi]
AB  - We evaluated an ex vivo photodepletion (PD) technique to selectively deplete 
      graft-versus-host disease (GVHD) alloreacting T cells given to 24 human leukocyte 
      antigen (HLA)-identical sibling stem cell transplantation (SCT) recipients. Donor 
      lymphocytes were activated by 72-hour exposure to irradiated in vitro expanded 
      recipient T lymphocytes and pulsed with a TH9402 photosensitizer. Alloactivated T 
      cells preferentially retaining the photosensitizer were eliminated by light 
      exposure. The PD product showed an inverted CD4(+)/CD8(+) ratio with greatest 
      depletion occurring in the CD4(+) naive and central memory populations. In 
      contrast, the CD8(+) naive and effector cells were relatively conserved, 
      reflecting the differential extrusion of TH9402 by T cell subsets. 
      Cytomegalovirus reactive T cells were reduced in the PD product and in recipient 
      blood 100 days after SCT when compared with contemporaneous HLA-identical sibling 
      donor T cell-depleted SCT recipients. Although PD SCT recipients experienced 
      similar absolute lymphocyte counts during the first 100 days after SCT, they 
      achieved 100% donor T cell chimerism more rapidly and had higher CD8(+) naive T 
      cell counts early after SCT. SCT recipients of PD products with the lowest CD4 
      central memory content had the highest risk of developing chronic GVHD (cGVHD) (P 
      = .04) and a poorer survival (P = .03). Although the persistence of CD8(+) naive 
      T cells may have contributed to important antileukemia responses resulting in a 
      relatively low relapse rate, our findings emphasize the role of donor memory T 
      cells and CD4 cells in establishing immune competence post-SCT. Although PD is 
      associated with excellent outcomes in the haploidentical setting, the low 
      frequency of alloactivations in HLA-matched pairs makes the PD approach used by 
      our group for allodepletion in HLA-matched sibling transplantations an 
      inefficient technique.
CI  - Published by Elsevier Inc.
FAU - McIver, Zachariah A
AU  - McIver ZA
AD  - Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood 
      Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. 
      mciverza@nhlbi.nih.gov
FAU - Melenhorst, Jan J
AU  - Melenhorst JJ
FAU - Grim, Andrew
AU  - Grim A
FAU - Naguib, Nicholas
AU  - Naguib N
FAU - Weber, Gerrit
AU  - Weber G
FAU - Fellowes, Vicki
AU  - Fellowes V
FAU - Khuu, Hahn
AU  - Khuu H
FAU - Stroncek, David S
AU  - Stroncek DS
FAU - Leitman, Susan F
AU  - Leitman SF
FAU - Battiwalla, Minoo
AU  - Battiwalla M
FAU - Barrett, A John
AU  - Barrett AJ
LA  - eng
GR  - Z99 HL999999/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110530
PL  - United States
TA  - Biol Blood Marrow Transplant
JT  - Biology of blood and marrow transplantation : journal of the American Society for 
      Blood and Marrow Transplantation
JID - 9600628
RN  - 0 (HLA Antigens)
RN  - 0 (Photosensitizing Agents)
RN  - 0 (Rhodamines)
RN  - RVY229824B (4,5-dibromorhodamine 123)
SB  - IM
MH  - CD4-CD8 Ratio
MH  - Female
MH  - HLA Antigens/*immunology
MH  - Hematopoietic Stem Cell Transplantation/*methods
MH  - Hematopoietic Stem Cells/*drug effects/immunology
MH  - Humans
MH  - Lymphocyte Depletion/*methods
MH  - Male
MH  - Photosensitizing Agents/*therapeutic use
MH  - Rhodamines/*therapeutic use
MH  - Siblings
MH  - T-Lymphocyte Subsets/*drug effects/immunology
MH  - T-Lymphocytes/drug effects/immunology
MH  - Tissue Donors
MH  - Treatment Outcome
PMC - PMC3179560
MID - NIHMS303786
EDAT- 2011/06/21 06:00
MHDA- 2012/06/01 06:00
PMCR- 2012/12/01
CRDT- 2011/06/21 06:00
PHST- 2011/03/15 00:00 [received]
PHST- 2011/05/12 00:00 [accepted]
PHST- 2011/06/21 06:00 [entrez]
PHST- 2011/06/21 06:00 [pubmed]
PHST- 2012/06/01 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - S1083-8791(11)00236-9 [pii]
AID - 10.1016/j.bbmt.2011.05.017 [doi]
PST - ppublish
SO  - Biol Blood Marrow Transplant. 2011 Dec;17(12):1846-54. doi: 
      10.1016/j.bbmt.2011.05.017. Epub 2011 May 30.