Hematopoietic stem cell and natural killer cell transplantation

Abstract

Blood and bone marrow (BM) transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) are procedures that utilize autologous or allogeneic cells to reconstitute a hematopoietic system, after chemotherapy with or without total body irradiation (TBI) to treat cancer intensively or suppress the recipient immunologically to prevent rejection. When used to treat leukemia, the intent of most transplantation approaches in pediatrics is to decrease relapse by using very high doses of cancer therapy to overcome partially resistant cancer cells. Standard high-dose “preparative” regimens (myeloablative regimens) cause irreversible BM failure unless there is “rescue” by the stem cell infusion. While the intensity of therapy alone is sufficient to cure some resistant malignancies, allogeneic transplantation has been noted to add an immunotherapeutic benefit, termed the graft-versus-leukemia (GVL) effect. Sources of hematopoietic stem cells currently used for HSCT include BM, peripheral blood stem cells (PBSC), and umbilical cord blood (CB). Because intensive therapy associated with the transplantation process can result in organ damage, susceptibility to life-threatening infection, late effects such as growth delay, and immunologic complications such as graft-versus-host disease (GVHD), it is reserved for cancers not curable with standard chemotherapeutic approaches or where there is a significant survival advantage over less intense therapies. Traditional indications for HSCT in leukemia include first or subsequent relapse and the very highest risk subclassifications of leukemias in first remission. As chemotherapy and transplantation outcomes improve, and as more precise definitions of disease risk are discovered, indications for transplantation change. Therefore, careful dialogue between oncologists and transplant physicians should occur early in the course of therapy for high-risk leukemias to determine when or if a transplantation procedure is indicated.