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Transient myelosuppression after cancer chemotherapy is a well-established adverse effect of such treatments For most regimens, it is rapidly reversible and requires no intervention Some malignancies (eg, many leukemias, lymphomas, and chemotherapy-sensitive breast and small-cell lung carcino-
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mas) may demonstrate a higher cure rate with higher-dose therapy; however, associated with this approach is an increase in hematologic toxicity Administering the maximal tolerated chemotherapy dose and restoring all hematopoietic functions as rapidly as possible has led to evolution of the concept of hematopoietic progenitor cell (HPC) or stem cell transplant HPC transplants have also expanded somewhat into the therapy of certain nonmalignant disorders of hematopoiesis and hematologic function; examples are aplastic anemia, sickle cell anemia, thalassemia, myelodysplasia, amyloidosis, and paroxysmal nocturnal hemoglobinuria The sources of HPC are the bone marrow, peripheral blood, and cord blood They comprise less than 05 1% of all nucleated bone marrow cells Although HPCs are rare cells, they can be obtained from the peripheral blood by apheresis As the peripheral blood has approximately one-fortieth the number of circulating HPCs as the bone marrow, these cells must be mobilized by the administration of cytotoxic chemotherapy (with the harvest being performed during the recovery phase) or enriched by the administration of hematopoietic growth factors The cells are frozen and administered at a later date Transplantation of HPC from umbilical cord blood can be used in unrelated donors, with a potentially lower rate of graft-versus-host disease, or may be autologous, from frozen stored blood Because syngeneic transplants between identical (monozygotic) twins are rare, the two predominant transplants are autologous, where the HPCs are harvested from and returned to the patient; or allogeneic, where the source is an HLAmatched donor, ideally a sibling The goals of the two procedures and their associated adverse effects are frequently different Allogeneic transplants are most commonly offered to patients with malignant and nonmalignant disorders involving the bone marrow Chemotherapy is given to ablate the marrow, resulting in maximal suppression or eradication of the recipient s native immune system The bone marrow is repopulated by infusion of donor cells containing not only HPCs but also functional donor T lymphocytes These T cells can cause graft-versus-host disease, in which the recipient s tissues are recognized as nonself While this is occasionally desirable, as in the graft-versus-leukemia effect, it is the cause of considerable morbidity and can be fatal There are two separate phases of graft-versus-host disease: acute, secondary to cytokinemediated cytotoxicity against the cells of the liver, the mucosa of the gastrointestinal tract, and skin; and chronic, characterized by fibrosis and collagen deposition and resembling autoimmune disease such as scleroderma The incidence of graft-versus-host disease can be decreased by depleting the donor marrow of T cells, but this is associated with a higher incidence of graft failure and, in the case of leukemia, a higher relapse rate Allogeneic peripheral HPC transplants have been attempted, and graft-versus-host disease in such cases does not appear to be as severe Autologous HPC transplants are performed solely for the treatment of malignancies In these cases the chemotherapy is intensively myelosuppressive although not necessarily myeloablative One prominent exception is patients with chronic myelogenous leukemia in blast crisis, who receive their autologous HPC in an effort to return their disease to the chronic phase Since patients usually have some residual
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Horwitz ME et al Chronic graft-versus-host disease Blood Rev 2006 Jan;20(1):15 27 [PMID: 16426941] Kalil AC et al Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients Ann Intern Med 2005 Dec 20;143(12):870 80 [PMID: 16365468] Nankivell BJ et al The natural history of chronic allograft nephropathy N Engl J Med 2003 Dec 11;349(24):2326 33 [PMID: 14668458] Shizura JA et al Hematopoietic stem and progenitor cells Clinical and preclinical regeneration of the hematolymphoid system Ann Rev Med 2005;56:509 38 [PMID: 15660525] Strom TB Rejection More than the eye can see N Engl J Med 2005 Dec 1;353(22):2394 6 [PMID: 16319390] Vats A et al Stem cells Lancet 2005 Aug 13 19;366(9485):592 602 [PMID: 16099296] Wagner JE et al; Unrelated Donor Marrow Transplantation Trial Effect of graft-versus-host disease prophylaxis on 3year disease free survival in recipients of unrelated donor bone marrow (T-cell Depletion Trial): a multi-centre, randomized phase II-III trial Lancet 2005 Aug 27 Sep 2;366 (9487):733 41 [PMID: 16125590]
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immune function and are receiving their own HPC and thus do not require posttransplant immunosuppression the risk of opportunistic infections and immunosuppression-related neoplasia is markedly reduced The success rates of HPC transplantation depend mostly on the underlying disease and the associated risk of relapse (in cases of leukemia), the level of matching between donor and recipient (and thus the likelihood of graft-versus-host disease), the age of the recipient, and the complications associated with conditioning (veno-occlusive liver disease and infection) Chronic graft-versus-host disease can lead to scleroderma-like or sicca-type syndromes Overall, the survival rates at 1 year are about 60 70% in aplastic anemia and 40 75% in various forms of leukemia and other neoplasms such as non-Hodgkin s lymphomas; results in breast carcinoma are less well defined
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Copelan EA Hematopoietic stem-cell transplantation N Engl J Med 2006 Apr 27;354(17):1813 26 [PMID: 16641398] Halloran PF Immunosuppressive drugs for kidney transplantation N Engl J Med 2004 Dec 23;351(26):2715 29 [PMID: 15616206]
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