After hematopoietic stem cell transplant from a HLA-matched donor, recipient blood and marrow cells are gradually replaced by donor cells. Monitoring chimerism during this engraftment is technically demanding. With assistance from Mitchell Horwitz in NIAID and Richard Childs in NHLBI, using commercial reagents designed for PCR-based microsatellite identification, we have developed assays to detect and quantitate donor cell chimerism post-transplant. These methods can detect 1-5 % donor cells. Since donor engraftment in different cell compartments may vary considerably, we typically measure chimerism in CD14/15 and CD3 cells from the peripheral blood in all transplant patients undergoing non-myeloablative transplant. The resulting information about donor cell engraftment in individual patients is extremely valuable both for clinical and investigational purposes. In particular, chimerism data is used extensively by NIH clinicians in deciding when to use immunosuppressive drugs (to prevent unwanted damage by donor cells), and when to administer donor lymphocyte infusions (to promote donor-mediated destruction of cancer or unwanted host cells). In monitoring a substantial number of patients, we can recognize several distinct patterns of engraftment. Some patients engraft both CD3 and CD14/15 cells very quickly, while others receiving similar treatment engraft one or the other cell type more slowly or not at all. These patterns imply major differences in host immune response to transplantation. With time we hope to identify more subtle features useful in predicting in advance graft-versus-host disease and graft suppression of tumor growth. Using serial host chimerism data in conjunction with in vitro measurements of alloreactivity (using ELISPOT based assays described in a related project) we hope to gain mechanistic insights into the role alloreactive T cells play in engraftment. Our ultimate goal would be to identify factors useful in monitoring and predicting the magnitude of graft-versus-host disease and graft-versus-tumor responses.

National Institute of Health (NIH)
Clinical Center (CLC)
Intramural Research (Z01)
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Savani, Bipin N; Mielke, Stephan; Rezvani, Katayoun et al. (2007) Absolute lymphocyte count on day 30 is a surrogate for robust hematopoietic recovery and strongly predicts outcome after T cell-depleted allogeneic stem cell transplantation. Biol Blood Marrow Transplant 13:1216-23
Savani, B N; Mielke, S; Adams, S et al. (2007) Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia. Leukemia 21:2145-52
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Montero, Aldemar; Savani, Bipin N; Kurlander, Roger et al. (2005) Lineage-specific engraftment and outcomes after T-cell-depleted peripheral blood stem cell transplant with Flu/Cy/TBI conditioning. Br J Haematol 130:733-9
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Solomon, Scott R; Mielke, Stephan; Savani, Bipin N et al. (2005) Selective depletion of alloreactive donor lymphocytes: a novel method to reduce the severity of graft-versus-host disease in older patients undergoing matched sibling donor stem cell transplantation. Blood 106:1123-9
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