Adjustment of Immonosuppressants Based on T Lymphocyte Chimerism Following Allogeneic Hematopoietic Stem Cell Transplantation.

Twenty-eight patients with a median age of 38 (15~54) years received allogeneic peripheral blood stem cell transplantation (allo-HSCT). Diagnoses included AML (n=7), ALL (n=2), CML (n=13), MM (n=4), MDS (n=1) and advanced ovarian cancer (n=1). Thirteen patients of them had progressive diseases. Myeloablative conditioning was given to 12 patients and non-myeloablative conditioning to 16 patients. FACS sorted granulocytes, T lymphocytes, B lymphocytes and NK cells from peripheral blood of all patients were analyzed for PCR amplification of short tandem repeats. The purity of sorted cells was above 96%. On day 7 posttransplant, the chimerism of NK cells was the highest in 88.5% patients, indicating that NK cells were the earliest engrafting cells. The subpopulations of granulocytes, B lymphocytes and NK cells reached complete chimerism (CC) on a median of day 14 posttransplant, while T lymphocytes were the latest subpopulation to reach CC in both myeloablative and non-myeloablative transplant on a median of day 21 and day 28 posttransplant, respectively. Seven patients with myeloid malignancy had molecular omen of graft rejection or disease relapse. Three patients of them had chimerism of donor T cells shifting from CC to MC only, while other subpopulation of cells remained CC. T cell chimerism in 2 patients of them remained lowest level among all subpopulation of cells. Recipient T cells had decreasing MC in 5 cases after discontinuance of immunosuppressant and donor lymphocyte infusion, 3 of them achieved CC again. Eight cases developed acute GVHD in 19 stable CC patients. Seven of them had GVHD after CC was achieved by all cell subsets. None of the patients in unstable CC group developed GVHD before they had graft rejection or relapse. The rate of acute GVHD of CC group was higher than MC group(χ²=4.25, P<0.05). We conclude that donor T lymphocytes are the earliest subpopulation of cells to subside during the course of graft rejection and disease relapse in myeloid malignancy. Patients responding to adjustment of immunosuppressants and/or DLI could achieve CC of T lymphocyte fraction again. CC of T lymphocyte could be a marker of stable engraftment of donor cells. Progressive MC of T cell is the omen of graft rejection and disease relapse. Immunosuppressant dosage should be adjusted according to T lymphocyte chimerism for different patients. GVHD prevention should be preferred in patients who reach CC in T cell fraction in one month after transplant. Therefore we suggest the patients might be given higher dose and longer period of immunosuppressants in 3 months posttransplant. In order to promote the engraftment of donor cell and avoid disease recurrence, the immunosuppressants might be tapered in the patients who do not reach CC in T cell fraction in one month after transplant and the patients with progressive MC in T cell.