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  • Image not available.Hematopoietic stem cell transplantation (HSCT) is a process that involves intravenous infusion of hematopoietic stem cells from a donor into a recipient, after the administration of chemotherapy with or without radiation. The rationale is to increase tumor cell kill by increasing the dose of chemotherapy. Immune-mediated effects contribute to the tumor cell kill observed after allogeneic HSCT.
  • Image not available. Hematopoietic stem cells used for transplantation can come from the recipient (autologous) or from a related or unrelated donor (allogeneic). If the related donor is a twin, the transplant is referred to as a syngeneic transplant.
  • Image not available.Human leukocyte antigen (HLA) mismatching of allogeneic donor/recipient pairs at either a class I or class II locus correlates with the risk of graft failure, graft-versus-host disease (GVHD), and survival. The ideal donor is matched at HLA-A, HLA-B, HLA-C, and HLA-DRB1.
  • Image not available. Hematopoietic stem cells are found in the bone marrow, peripheral blood, and umbilical cord blood. Because of their rarity and their similarity to other cells, hematopoietic stem cells are difficult to isolate and measure. These stem cells express the CD34 antigen, and quantification of the number of CD34+ cells has become a clinically useful measure of the number of hematopoietic stem cells.
  • Image not available. Because of clinical and economic advantages, peripheral blood has replaced bone marrow as the source of hematopoietic stem cells in the autologous and adult allogeneic HSCT setting. Bone marrow continues to be the primary graft source in children undergoing allogeneic HSCT.
  • Image not available. The purpose of the preparative (or conditioning) regimen in traditional myeloablative transplants is twofold: (a) maximal tumor cell kill and (b) immunosuppression of the recipient to reduce the risk of graft rejection (allogeneic HSCT only).
  • Image not available. Reduced-intensity conditioning regimens (including those that are nonmyeloablative) reduce early posttransplant morbidity and mortality while maximizing the graft-versus-malignancy (GVM) effect of the allogeneic graft. The advantage of this approach is that patients who otherwise would not be eligible for allogeneic HSCT can be offered a potentially curative therapy.
  • Image not available. Posttransplant immunotherapy is based on the GVM effect caused by certain subsets of T cells responsible for eradication of malignant cells. Posttransplant immunotherapy includes the use of donor lymphocyte infusions, immunomodulatory cytokines, monoclonal antibodies, or antitumor vaccines.
  • Image not available. Transplant-related mortality associated with allogeneic HSCT ranges from 10% to 80%, depending on age, donor, and disease status. Major causes of death include infection, organ toxicity, and GVHD. The most common cause of death after autologous HSCT is disease relapse. Transplant-related mortality usually is less than 5%, depending on the conditioning regimen, age, and disease status.
  • Image not available. Treatment of acute GVHD often is unsuccessful, and the resulting complications can be fatal. Patients undergoing allogeneic HSCT are given prophylactic immunosuppressive therapy, which inhibits T-cell activation and/or proliferation. The most commonly used GVHD prophylaxis regimen is cyclosporine or tacrolimus and methotrexate.
  • Image not available. Initial treatment of both acute and chronic GVHD consists of prednisone, either alone or combined with cyclosporine or tacrolimus. Treatment of patients with steroid-refractory GVHD is problematic.

On completion of the chapter, the reader will ...

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