PMID- 16219539
OWN - NLM
STAT- MEDLINE
DCOM- 20051202
LR  - 20201212
IS  - 0301-472X (Print)
IS  - 0301-472X (Linking)
VI  - 33
IP  - 10
DP  - 2005 Oct
TI  - Responses to donor lymphocyte infusion for acute lymphoblastic leukemia may be 
      determined by both qualitative and quantitative limitations of antileukemic 
      T-cell responses as observed in an animal model for human leukemia.
PG  - 1172-81
AB  - OBJECTIVE: Donor lymphocyte infusion (DLI) after allogeneic stem cell 
      transplantation is largely unsuccessful in the treatment of acute lymphoblastic 
      leukemia (ALL). To allow identification of the causes of this failure, we 
      established an animal model of DLI in human ALL. METHODS: NOD/scid mice were 
      inoculated with primary human ALL cells. Cells from five different patients were 
      studied. After engraftment, DLI was performed by infusion of human leukocyte 
      antigen (HLA)-identical donor T cells or HLA-disparate donor T cells. RESULTS: 
      DLI resulted in expansion of activated, leukemia-reactive T cells in all 
      donor-patient combinations. After 40 days of expansion, T cells abruptly declined 
      in numbers and displayed loss of cytotoxicity. At this moment, remissions were 
      observed in three of five donor-patient combinations. In animals engrafted with 
      the two unresponsive ALL, remissions could be achieved when HLA-disparate DLI was 
      given. CONCLUSION: Our results indicate that the inefficacy of DLI in ALL may be 
      due to the limitation of the proliferative capacity of ALL-reactive T cells and 
      that the antileukemic efficacy during the limited time span of proliferation 
      depends on the antigenic disparity between the donor and the patient. The model 
      can be used to study whether alternative strategies may result in more sustained 
      antileukemic responses after DLI in ALL.
FAU - Nijmeijer, Bart A
AU  - Nijmeijer BA
AD  - Leiden University Medical Center, Leiden, The Netherlands. b.a.nijmeijer@lumc.nl
FAU - van Schie, Marianke L J
AU  - van Schie ML
FAU - Verzaal, Perry
AU  - Verzaal P
FAU - Willemze, Roel
AU  - Willemze R
FAU - Falkenburg, J H Frederik
AU  - Falkenburg JH
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
SB  - IM
MH  - Adult
MH  - Animals
MH  - Cell Proliferation
MH  - Cytotoxicity, Immunologic/immunology
MH  - Female
MH  - Graft vs Leukemia Effect/*immunology
MH  - Humans
MH  - Immunity, Cellular/immunology
MH  - Leukemia, Experimental/*immunology
MH  - *Living Donors
MH  - *Lymphocyte Transfusion/methods
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasm Transplantation/immunology
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/*immunology/therapy
MH  - Stem Cell Transplantation
MH  - T-Lymphocytes/*immunology/transplantation
MH  - Transplantation, Homologous
EDAT- 2005/10/13 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/10/13 09:00
PHST- 2005/01/28 00:00 [received]
PHST- 2005/06/06 00:00 [revised]
PHST- 2005/06/28 00:00 [accepted]
PHST- 2005/10/13 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/10/13 09:00 [entrez]
AID - S0301-472X(05)00357-7 [pii]
AID - 10.1016/j.exphem.2005.06.034 [doi]
PST - ppublish
SO  - Exp Hematol. 2005 Oct;33(10):1172-81. doi: 10.1016/j.exphem.2005.06.034.