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INTRODUCTION

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SUMMARY

Over the past 60 years, the field of hematopoietic cell transplantation (HCT) has evolved from experimental animal models of marrow transplantation to curative therapy for tens of thousands of people yearly who are affected by a wide variety of marrow failure states, myeloid and lymphoid malignancies, immune deficiencies, and inborn errors of metabolism. Advances in transplantation immune biology combined with improvements in supportive care have made this evolution possible and have ushered in the modern era of HCT. This chapter discusses the biologic principles and clinical applications of HCT along with its future applications. Selected results demonstrating important principles are highlighted.

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Acronyms and Abbreviations:

ALL, acute lymphoblastic leukemia; ALK+, anaplastic lymphoma kinase–positive; AML, acute myeloid leukemia; APC, antigen-presenting cells; ASBMT, American Society for Blood & Marrow Transplantation; ATG, antithymocyte globulin; BCNU, 1,3-bis(2-choloroethyl)-1-nitrosurea; BEAM, BCNU, etoposide, cytarabine, and melphalan; BMT-CTN, Blood & Marrow Transplant Clinical Trials Network; BU, busulfan; CIBMTR, Center for International Blood and Marrow Transplant Research; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CMV, cytomegalovirus; CR, complete remission; CR1, first complete remission; CT, computed tomography; CXCL12, extracellular-matrix-bound stromal cell–derived factor-1; CXCR4, chemokine-related receptor 4; CY, cyclophosphamide; DAH, diffuse alveolar hemorrhage; DLI, donor lymphocyte infusion; EBMT, European Society for Blood and Marrow Transplantation; ECP, extracorporeal photopheresis; FDG, 18-fluorodeoxyglucose; FLU, fludarabine; G-CSF, granulocyte colony-stimulating factor; GI, gastrointestinal; GM-CSF, granulocyte-monocyte colony-stimulating factor; GVHD, graft-versus-host disease; GVT, graft-versus-tumor; HCT, hematopoietic cell transplantation; HCT-CI, HCT-specific Comorbidity Index; HL, Hodgkin lymphoma; HLA, human leukocyte antigen; HSC, hematopoietic stem cell; HSV, herpes simplex virus; IFN, interferon; Ig, immunoglobulin; IL, interleukin; IPS, idiopathic pneumonia syndrome; KTLS, c-kit+, Thy-1.1lo, lineage marker–/lo, and Sca-1+; MDS, myelodysplastic syndrome; MHC, major histocompatibility complex; MMF, mycophenolate mofetil; MSC, mesenchymal stromal cell; MTX, methotrexate; NHL, non-Hodgkin lymphoma; NIH, National Institutes of Health; NK, natural killer; NMDP, National Marrow Donor Program; PAM, Pretransplant Assessment of Mortality; PBPC, peripheral blood progenitor cell; PCA, patient-controlled anesthesia; PCR, polymerase chain reaction; PET, positron emission tomography; Ph, Philadelphia chromosome; PSGL-1, P-selectin glycoprotein ligand-1; PTLD, posttransplantation lymphoproliferative disorder; RIC, reduced-intensity conditioning; SCID, severe combined immunodeficiency; SOS, sinusoidal obstruction syndrome; SRL, sirolimus; TAC, tacrolimus; TBI, total-body irradiation; Th, T-cell helper; TKI, tyrosine kinase inhibitor; TLI, total lymphoid irradiation; TNF, tumor necrosis factor; TPN, total parenteral nutrition; Treg, regulatory T cell; TRM, transplant-related mortality; UCB, umbilical cord blood; VCAM, vascular cell adhesion molecule; VOD, venoocclusive disease; VZV, varicella-zoster virus.

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HISTORY

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The successful clinical application of hematopoietic cell transplantation (HCT) required a century of key developmental discoveries (Table 23–1). Between 1868 and 1906, European and American investigators established that marrow cells were the source of blood cell production. In 1939, the first documented human marrow transplant was performed in a patient with gold-induced marrow aplasia.1 The patient was infused intravenously with marrow from a brother with an identical ABO blood type. The transplant was not successful, and the patient ...

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