Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning

Abstract

Summary Nonmyeloablative or reduced-intensity conditioning regimens have been used to condition elderly or ill patients with hematological malignancies for allogeneic hematopoietic cell transplantation (HCT). Initial mixed donor/host chimerism (i.e. the coexistence of hematopoietic cells of host and donor origin) has been observed in most patients after such transplants. Here, we describe both factors affecting engraftment kinetics in patients given a nonmyeloablative or a reduced-intensity conditioning, and associations between peripheral blood cell subset chimerism levels and HCT outcomes. c 2004 Elsevier Ltd. All rights reserved. KEYWORDSHematopoietic cell transplantation; Nonmyeloablative; Chimerism; Engraftment Reduced-intensity and nonmyeloablative conditioning regimens for allogeneic HCTTo avoid serious regimen-related toxicities, the use of conventional allogeneic hematopoietic cell transplantation (HCT) has been restricted to younger and medically fit patients. 1 This is unfortunate since the median age at diagnosis for patients with hematological malignancies such as acute and chronic leukemias, lymphomas, multiple myeloma or myelodysplastic syndromes, ranges from 65 to 70 years, 2 thereby precluding the use of allogeneic HCT for most patients with these diseases. The curative potential of allogeneic HCT has been ascribed not only to the eradication of malignant cells by high-dose chemotherapy and total body irradiation, but also to immune-mediated graft-versustumor (GVT) effects. [3][4][5] The power of the 0268-960X/$ -see front matter c

Increasing mixed chimerism and the risk of graft loss in children undergoing allogeneic hematopoietic stem cell transplantation for non-malignant disorders

“…4,11,15 Andreani et al 13 showed an 84% rejection rate in patients with thalassemia who had 425% autologous cells in WB at 2 months post transplant, and Baron et al 1,2 and Matthes-Martin et al 5 showed that low donor CD3 þ and natural killer cell chimerism at days 14 and 28 post transplant correlated with graft rejection. Long-term follow-up of patients with thalassemia showed that once tolerance to donor cells has been established, graft rejection does not occur even at low levels (o10%) of donor WB engraftment.…”

“…The study included 24 children (median age 7.6 years, range (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)) undergoing first unmodified allogeneic HSCT for a non-malignant disorder at University of California, San Francisco, (UCSF) Children's Hospital, Pediatric Blood and Marrow Transplant Unit (PBMTU) between January 2001 and March 2007. Only patients who received fludarabine-or cyclophosphamide-based conditioning regimen and had chimerism testing done by the STR technique were included.…”

“…1,2,5 Graft function. The graft was considered functional if it resulted in correction of the underlying disease.…”

“…1,2 Mixed chimerism (MC) is related to increased risk of relapse in patients with acute leukemia, and low levels of donor CD3 þ and natural killer cell chimerism correlate with an increased risk of graft rejection. [3][4][5] However, the presence of MC is associated with a decreased incidence of acute graft-versus-host disease (aGVHD).…”

Bone marrow graft as a source of allogeneic hematopoietic stem cells in patients undergoing a reduced intensity conditioning regimen

“…5 This choice is explained by the high level of CD34 + cells and T lymphocytes in PBSC grafts, which allows a better engraftment than BM grafts. [8][9][10][11][12] However, PBSC has also been shown to increase the risk of chronic GVHD (cGVHD) compared with BM. [13][14][15][16] Such a complication affects patients' quality of life and is associated with a higher risk of infections and death.…”