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Keil, F; Prinz, E; Moser, K; Mannhalter, C; Kalhs, P; Worel, N; Rabitsch, W; Schulenburg, A; Mitterbauer, M; Greinix, H.
Rapid establishment of long-term culture-initiating cells of donor origin after nonmyeloablative allogeneic hematopoietic stem-cell transplantation, and significant prognostic impact of donor T-cell chimerism on stable engraftment and progression-free survival.
Transplantation. 2003; 76(1):230-236 Doi: 10.1097/01.TP.0000071862.42835.76
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Co-Autor*innen der Med Uni Graz
Greinix Hildegard
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Abstract:
Nonmyeloablative allogeneic hematopoietic stem-cell transplantation (NST) allows establishment of donor hematopoiesis without eradication of recipient stem cells by chemoradiotherapy. Quantification of donor chimerism may predict graft failure and relapse. We quantified donor long-term culture-initiating cells (LTC-IC) in nine patients during the early phase after NST and lineage-specific donor cells of myeloid (CD33+, CD34+, granulocytes) and lymphoid lineage (CD3+, CD4+, CD8+, CD56+) in 38 patients with a median follow-up of 40 weeks after NST. Conditioning therapy consisted of fludarabine 90 mg/m2 followed by total body irradiation of 2 Gy. Only rapid establishment of donor T-cell chimerism was essential for stable donor engraftment. Patients with less than 90% of donor T cells 4 weeks after NST had a significantly higher risk of relapse, graft rejection, or both (14 of 18 patients) than patients with donor T-cell chimerism of 90% and higher (3 of 20 patients). Although conditioning therapy was nonmyeloablative, a significant decrease of repopulating stem cells defined as LTC-IC was seen after 2 weeks followed by rapid recovery of LTC-IC to pretransplant values. Interestingly, all LTC-IC were from donor origin 2 and 4 weeks after NST, but rapid establishment of donor LTC-IC was not predictive for progression-free survival. Rapid establishment of lymphoid but not myeloid donor chimerism is a prognostic factor for stable donor engraftment after NST. It seems that an immunologic shield of alloreactive donor T cells is essential for early hematopoietic progenitors.
Find related publications in this database (using NLM MeSH Indexing)
ABO Blood-Group System -
Adolescent -
Adult -
Aged -
Antigens, CD - blood
Blood Group Incompatibility -
Cell Culture Techniques - methods
Disease-Free Survival -
Female -
Graft vs Host Disease - prevention & control
Hematopoietic Stem Cells - cytology
Humans -
Immunosuppressive Agents - therapeutic use
In Situ Hybridization, Fluorescence -
Leukemia - therapy
Male -
Middle Aged -
Neoplasms - therapy
Prognosis -
Stem Cell Transplantation - methods
T-Lymphocytes - immunology
Tissue Donors -
Transplantation Chimera - immunology
Transplantation, Autologous -
Transplantation, Homologous -
Treatment Outcome -

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