Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Keil, F. et al.

Keil, Prinz, Moser, Mannhalter, Kalhs, Worel, Rabitsch, Schulenburg, Mitterbauer, Greinix,

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.[1]

References

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. Keil, F., Prinz, E., Moser, K., Mannhalter, C., Kalhs, P., Worel, N., Rabitsch, W., Schulenburg, A., Mitterbauer, M., Greinix, H. Transplantation (2003) [Pubmed]

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