학술논문

Complete donor T cell chimerism is accomplished in patients transplanted with bone marrow grafts containing a fixed low number of T cells.
Document Type
Academic Journal
Author
Verdonck LF; Department of Haematology, University Hospital Utrecht, The Netherlands.; van Blokland WTBosboom-Kalsbeek EKvan Heugten HGTilanus MGde Weger RA
Source
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8702459 Publication Model: Print Cited Medium: Print ISSN: 0268-3369 (Print) Linking ISSN: 02683369 NLM ISO Abbreviation: Bone Marrow Transplant Subsets: MEDLINE
Subject
Language
English
ISSN
0268-3369
Abstract
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.