A recent retrospective data analysis from the laboratory of Dr. John Barrett of NHLBI studied the relationship between peripheral blood counts post transplant, chimerism, and clinical outcome in patients undergoing allotransplantation for the treatment of recurrent leukemia. The studies demonstrated that a high concentration of circulating lymphocytes at day 30 posttransplant was a positive predictor of rapid donor engraftment in the myeloid compartment, reduced recurrence of AML, reduced GVH, and improved survival. Additional analysis indicated the level of circulating NK cells at day 30 to be a particularly important predictor of outcome. These studies also demonstrated that the infusion of a larger CD34 cells dose at the time of transplantation also favorably affects these measures of clinical outcome.? ? Several recent protocols treat stem cell recipients with stem cells from two or more donors to hasten reconstitution or treat leukemic recurrence. In some cases, this involved the infusion of human umbilical cord stem cells from two separate donors. In other cases, a combination of peripheral blood T cells and stems cells from an HLA-matched donor plus CD34 cells from another haploidentical relative were used in combination. Individualizing a strategy to unequivocally identify cell populations from 2 or more related donors and compute % chimerism has been technically challenging, but to date we have been able to successfully distinguish cells from the recipient and each of the donors in every case. We anticipate the continued attempts to use multiple donors for engraftment in the coming year. ? ? A recently adopted NCI protocol uses highly T cell depleted stem cell preparations to reconstitute patients with aggressive lymphoproliferative malignancy. In several instances, disease progress in this group has forced institute investigators to administer additional chemotherapy shortly after donor cell transfer. Consequently, we have noted early graft failure in several of these patients. Through close monitoring of chimerism for graft failure and frequent communication with the responsible investigators, these patients were promptly recognized and retreated with a second stem cell infusion. In each case, successful engraftment was obtained after the second infusion. The findings illustrate the extreme sensitivity of recently transplanted stem cells to chemotherapeutic agents.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL010334-07
Application #
7733634
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2008
Total Cost
$29,796
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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; 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, 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