During the past year, we have collaborated Dr. John Tisdale in monitoring stem cell engraftment in children and young adults transplanted for amelioration of sickle cell anemia. Given the relatively benign clinical course in patients with sickle cell anemia in the absence of transplant, Dr. Tisdale elected to minimize the risk of potentially life-threatening graft versus host disease (GVHD) by using a very low intensity conditioning regimen (rapamycin and low intensity whole body irradiation). This regime is sufficent to assure myeloid stem cell engraftment while minimizing the engraftment of donor T cells in the recipient. Using this regimen, Dr. Tisdale has so far transplanted matched allogeneic stem cells into 5 patients. To date four of these patients have engrafted sufficient myeloid precursors to correct erythropoiesis. In one instance, a second stem cell infusion was required because of graft rejection, and in one patient the graft failed. The clinical course in patients successfully transplanted has been excellent, with minimal GVHD. We will continue our collaboration with Dr. Tisdale as he further perfects his engraftment conditions and extends his very promising studies.? Studies monitoring engraftment in Dr. Barretts patients receiving selectively T cell-depleted grafts continue. Of relevance, Dr. Barrett is in the process of initiating a new protocol using a new method (photodepletion) for selective depletion of alloreactive donor T cells. Clinical accrual into this protocol should begin during the coming year.
|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|
|Savani, Bipin N; Rezvani, Katayoun; Mielke, Stephan et al. (2006) Factors associated with early molecular remission after T cell-depleted allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 107:1688-95|
|Akpinar, Edip; Keary, Jodie M; Kurlander, Roger et al. (2005) Measurement of chimerism in cynomolgus monkeys using human-specific short tandem repeat-based assay. Transplantation 79:236-9|
|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|
|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|
|Carvallo, Cristian; Geller, Nancy; Kurlander, Roger et al. (2004) Prior chemotherapy and allograft CD34+ dose impact donor engraftment following nonmyeloablative allogeneic stem cell transplantation in patients with solid tumors. Blood 103:1560-3|