Complete donor T cell chimerism is accomplished in patients transplanted with bone marrow grafts containing a fixed low number of T cells.
T cell depletion of the bone marrow graft, the most effective method to prevent severe graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT), has resulted in approximately three times more relapses of the disease post-transplant than after non-T cell-depleted BMT. It has been hypothesized that this is caused by the development of mixed T cell chimerism, often observed after T cell depleted BMT, whereas non-T cell-depleted BMT generally results in complete donor T cell chimerism. In order to find an approach of T cell depletion which may avoid the high relapse rate but prevent severe GVHD, we gave marrow recipients a partial T cell-depleted marrow graft containing 1 x 10(5) donor T cells/kg recipient's weight. To investigate whether our approach results in complete donor T cell chimerism, we analyzed post-transplant the origin of purified T cells in 56 patients with hematologic malignancies, including 15 patients at the time they relapsed. The T cells were studied for being of host or donor origin by amplification of four loci of variable number of tandem repeats (VNTR) by PCR. From 6 months post-BMT, all 45 patients who could be analyzed in remission (five had died and six had relapsed within 6 months) had T cells that were exclusively of donor origin. Furthermore, the T cells of 15 patients who had relapsed post-BMT were also exclusively of donor origin. Severe GVHD was never observed. Thus, this approach seems to combine the favorable aspects of both T cell-depleted and non-T cell-depleted BMT.
Verdonck
L F
LF
Department of Haematology, University Hospital Utrecht, The Netherlands.
van Blokland
W T
WT
Bosboom-Kalsbeek
E K
EK
van Heugten
H G
HG
Tilanus
M G
MG
de Weger
R A
RA
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002678:Chimera; D005260:Female; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*