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Adverse reactions following blood transfusion reflect immunologic, pathophysiologic, and microbiologic events. This chapter presents information about transfusion-associated viral, bacterial, parasitic, and prion infections and discusses a number of emerging agents including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Transfusion-transmitted infection risk mitigation through blood donor screening and blood testing strategies are presented. The boxed discussions provide insights into interventions aimed at reducing risk from known and…

A transfusion reaction can be defined broadly as any adverse event that occurs in association with the infusion of a blood or cell therapy product. Transfusion reactions are classified by how close to transfusion they occur (timing), how much morbidity is caused (severity), how strong the causal association of the event is with transfusion (imputability), as well as by its fit to a (standardized) definition of…

Therapeutic bloodletting is an ancient therapy that dates back to the Galenic conceptualization of illness caused by the imbalance of the four humors. The practice remained fashionable, albeit unproved, well into the 19th century. About the time that scientific skepticism began to temper the widespread use of therapeutic phlebotomy, a new technique for blood removal, apheresis, appeared in the research laboratory. The term apheresis , derived…

Plasma and its derivatives are well-established clinical resources, but cost, risk of infectious disease transmission, although rare, and other adverse effects mandate their appropriate use. Even to this day, however, much still remains to be clarified regarding the appropriate clinical indications/protocols for plasma product use. Plasma can be separated from red blood cells (RBCs) through centrifugation of whole blood at the time of collection or can…

This chapter reviews human leukocyte antigen (HLA) and human neutrophil antigen (HNA) systems. A general background of the structure, function, and nomenclature of both systems and their relevance in clinical hematology is presented. Analysis of HLA gene products is applied in clinical settings (1) to select compatible donor-recipient pairs for transplantation, (2) to select HLA-compatible single-donor platelet products for thrombocytopenic patients refractory to standard transfusion of…

Platelet Collection and Manufacturing Platelet components are either prepared from whole blood donations (platelet concentrates) or are collected by apheresis (single donor platelets). In the United States, whole blood–derived platelet concentrates are produced using the platelet-rich plasma (PRP) method. First, a whole blood unit is separated by gentle centrifugation (slow spin) into red blood cells (RBCs) and PRP. The PRP is then centrifuged a second time…

The clinical practice of transfusion medicine has evolved substantially since the discovery of the ABO system around 1900. Two technological advances set the stage for clinical practice through blood component therapy. First, the introduction of a safe and effective anticoagulant-preservative solution (suggested by Loutit and Mollison) allowed for the preservation of blood products. Second, in the mid-1960s, the introduction of plastic blood bags by Walter and…

Pretransfusion testing includes ABO and Rhesus (Rh) type, and antibody screening to determine whether a patient has an unexpected red blood cell (RBC) antibody. If the antibody screen is positive, an identification panel is performed to identify the specificity. Unexpected antibodies can be clinically significant causing hemolysis (i.e., acute or delayed hemolytic reaction) after transfusion of RBCs carrying the reciprocal antigen, or can be insignificant. The…

Although hematopoietic cell transplantation (HCT) is a therapeutic option for various hematological and non-hematological disorders, it can result in toxicities and complications, leading to significant treatment related morbidity and non-relapse mortality (NRM). Based on the temporal association from the date of HCT, these may be divided into early complications (within the first 3 months of HCT) or late complications (beyond 3 months of HCT), but can…

The ability of allogeneic hematopoietic cell transplantation (HCT) to cure certain hematologic malignancies is widely recognized. An important therapeutic aspect of HCT in eradicating malignant cells is the graft-versus-leukemia (GVL) effect. The importance of the GVL effect in allogeneic HCT has been recognized since the earliest experiments in stem cell transplantation. Forty years ago, Barnes and colleagues noted that leukemic mice treated with a subtherapeutic dose…

Cord Blood as a Stem Cell Source It is well established that ethnic minorities have a low likelihood of matching with an unrelated hematopoietic stem cell donor. In recent years, there has been increasing interest in alternative stem cell donors given the genetic heterogeneity of our population coupled with diminishing family size. Cord blood (CB) represents an alternative donor type for hematopoietic cell transplantation (HCT) and…

Introduction Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective treatment for a wide range of hematologic malignancies, nonmalignant hematologic diseases, and immunologic disorders. Sources of donor stem cells for alloHSCT include human leukocyte antigen (HLA)-matched siblings (MSD), HLA-matched unrelated adult donors (MUD) matched at least at HLA-A, -B, -C, -DRB1, HLA-mismatched unrelated donors, unrelated umbilical cord blood, and HLA half-matched related donors, mismatched at 2…

The outcomes of unrelated donor hematopoietic cell transplantation (HCT) have greatly improved as a result of a better understanding of the diversity of human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) genes. The HLA and KIR genetic systems regulate the transplantation barrier. Clinical outcomes after unrelated donor transplantation can be achieved with donor matching for the highly polymorphic HLA loci and through consideration of donor…

Background Early reports of leukemia-free survival, following human leukocyte antigen (HLA)-identical sibling hematopoietic cell transplantation (HCT) for refractory acute leukemia, was reported in the 1970s. Since then, allogeneic HCT has evolved into an effective and increasingly safe, curative, and intent therapeutic modality for hematologic malignancies. The indications and applicability of HCT for specific diseases change over time, especially as non-transplant treatment options and our understanding of…

The use of gene transfer to treat human diseases has now been demonstrated to be efficacious in a growing number of indications. Proof-of-principle successes in several monogenic diseases—both hematologic and non-hematologic—have been published and widely publicized in the past decade. The previous occurrence of serious adverse events in some trials related to insertional mutagenesis has stimulated the development of safer vector systems and the improved efficiency…

It has been more than 70 years since allogeneic hematopoietic stem cells (HSC) were first transplanted to human recipients in the form of bone marrow. Since that time, the source of HSC has widened to include autologous bone marrow, growth factor mobilized peripheral blood progenitor cells (PBPCs), umbilical cord blood, and more. In parallel, there has been the development of other cellular therapies to treat a…

Hematopoietic stem cell (HSC) products for autologous or allogeneic transplantation are available from bone marrow (BM), peripheral blood, or umbilical cord blood (UCB) sources. Bone marrow was the original source of cells for transplantation because of the ease and reliability of collecting adequate numbers of cells for transplantation, and it remains the standard with which other sources of HSCs are compared. Peripheral blood stem cell (PBSC)…

The past several decades have seen a marked improvement in survival for patients with hematologic malignancies. The 5-year survival is as follows: leukemia, 66%; Hodgkin lymphoma (HL), 89%; non-Hodgkin lymphoma (NHL), 75%; and multiple myeloma (MM), 54%. As a consequence, the population of long-term cancer survivors continues to grow. As of January 1, 2019, there were 451,700 leukemia survivors living in the United States, 234,890 HL…

Palliative care for seriously ill children and adults is provided by an interdisciplinary team of clinicians who focus on communication about values and goals of care and ameliorating suffering from physical, social, spiritual, existential, and psychological concerns. Members of the interdisciplinary palliative care team include registered and advanced practice nurses, physician assistants, social workers, pharmacists, chaplains, and adult and pediatric physicians, many of whom are ABIM…

Relieving pain in patients with hematologic disorders requires a multifaceted approach. This chapter will provide the clinician with the tools to perform a systematic evaluation of the pain complaint and propose a rational, evidence-based, strategy. After the source and type of the pain has been identified and assessed, appropriate nonpharmacologic and pharmacologic therapies can be initiated. The approach to managing pain in hematologic disorders is largely…