A three-step method for preparing cryopreserved samples of apheresis products for post-thaw analysis yields a high recovery of viable cells.

Background: Flow cytometry protocols for counting fresh CD34+ cell samples are not ideal for cryopreserved products due to cryoprotectant cytotoxicity. For cryopreserved samples, often large volumes of hypotonic solutions, which can cause cell death, are used to remove the cryoprotectant with a post-thaw wash. We recently developed a novel multistep dilution method with subsequent flow cytometry analysis to allow for accurate and reproducible results.

A 3-step method for preparing cryopreserved samples of apheresis products for post-thaw analysis yields a higher percentage of viable cells.

Background: Standard flow cytometry protocols for CD34+ cell enumeration designed for fresh samples are not appropriate for cryopreserved products. Special protocols have been developed to remove the cryoprotectant by quickly washing a freshly thawed sample. Exposing cells to a large volume of hypotonic solution and subsequent washing process was hypothesized to cause lab-induced cell death.

Collection and processing of hematopoietic progenitor cell products at risk of presenting with cold agglutination.

Background Aims: Cold agglutinins are commonly identified in transfusion laboratories and are defined by their ability to agglutinate erythrocytes at 3-4°C, with most demonstrating a titer >64. Similarly, cryoglobulins can precipitate from plasma when temperatures drop below central body temperature, resulting in erythrocyte agglutination. Thankfully, disease associated from these autoantibodies is rare, but unfortunately, such temperature ranges are routinely encountered outside of the body's circulation, as in an extracorporeal circuit during hematopoietic progenitor cell (HPC) collection or human cell therapy laboratory processing.

Clinical impact of KIR haplotypes in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic hematopoietic stem cell transplantation.

To evaluate the impact of killer immunoglobulin-like receptor (KIR) genotyping in allogeneic hematopoietic stem cell transplantation for myeloid disorders at our institution, retrospective KIR genotyping was performed on 77 patients and their 10/10 matched unrelated donors. In a multivariate model including donor age, permissiveness, and presence of donor KIR B/x, an association with overall survival was observed ( = .047).

How do I warm HPC(A) products to maximize cell viability in the setting of cold agglutinin disease?

Background: High titers of cold agglutinins jeopardize the quality of an apheresis product meant for autologous or allogeneic transplant. Management of transplant patients with cold agglutinin disease (CAD) is often experience-based and under reported, yet decisions must be made quickly to optimize product management and patient outcomes. There remains a lack of data quantifying cell recovery and viability when using various warming methodologies.

New Developments in the Understanding and Treatment of Autoimmune Hemolytic Anemia: Traditional and Novel Tests.

Careful consideration of the clinical history with traditional testing such as an antibody screen and direct antiglobulin test (DAT) allow for the categorization of most forms of autoimmune hemolytic anemia. Based on the initial findings, specialized testing can further categorize disease entities and increase the sensitivity of testing. In this section, we explain the diagnostic findings of both traditional and novel testing and how their appropriate interpretations help distinguish the forms of autoimmune hemolytic anemia (AIHA).

Normal ex vivo mesenchymal stem cell function combined with abnormal immune profiles sets the stage for informative cell therapy trials in idiopathic pulmonary fibrosis patients.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive pulmonary disease characterized by aberrant tissue remodeling, formation of scar tissue within the lungs and continuous loss of lung function. The areas of fibrosis seen in lungs of IPF patients share many features with normal aging lung including cellular senescence. The contribution of the immune system to the etiology of IPF remains poorly understood.

Management of externally manufactured cell therapy products: the Mayo Clinic approach.

Background: The rise of investigative and commercially available cell therapy products adds a new dynamic to academic medical centers; that is, the management of patient-specific cell products. The scope of cell therapy has rapidly expanded beyond in-house collection and infusion of cell products such as bone marrow and peripheral blood transplant. The complexities and volumes of cell therapies are likely to continue to become more demanding.

Implementation of a Comprehensive Patient Blood Management Program for Hospitalized Patients at a Large United States Medical Center.

Objective: To assess changes in inpatient transfusion utilization and patient outcomes with implementation of a comprehensive patient blood management (PBM) program at a large US medical center.

Patients And Methods: This is an observational study of graduated PBM implementation for hospitalized adults (age ≥18 years) from January 1, 2010, through December 31, 2017, at two integrated hospital campuses at a major academic US medical center. Allogeneic transfusion utilization and clinical outcomes were assessed over time through segmented regression with multivariable adjustment comparing observed outcomes against projected outcomes in the absence of PBM activities.

Antibody incidence and red blood cell transfusions in patients on daratumumab.

Background: Daratumumab (Dara), an anti-CD38 monoclonal antibody for hematologic malignancies, interferes with routine blood bank testing, specifically affecting the antibody screen and identification panels. In 2016, the AABB recommended performing a baseline phenotype or genotype before a patient (Pt) begins taking anti-CD38 to avoid this interference and potential problems with transfusion. The objective of this study was to assess red blood cell (RBC) utilization and subsequent incidence of alloimmunization to the transfused RBCs in patients receiving Dara.

To Give or Not to Give: RhD Immunoglobulin for an * Pregnant Woman with Sickle Cell Disease.

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations.

Sensitive detection of integrated and free transcripts in chimeric antigen receptor T-cell manufactured cell products using droplet digital polymerase chain reaction.

Background Aims: Viral vectors are commonly used to introduce chimeric antigen receptor (CAR) constructs into cell therapy products for the treatment of human disease. They are efficient at gene delivery and integrate into the host genome for subsequent replication but also carry risks if replication-competent lentivirus (RCL) remains in the final product. An optimal CAR T-cell product should contain sufficient integrated viral material and no RCL.

In from the cold: M-protein light chain glycosylation is positively associated with cold agglutinin titer levels.

Background: Primary cold agglutinin disease (CAD) is a monoclonal antibody (M-protein) and complement-mediated chronic hemolytic disease process. Antibody glycosylation can play a role in both antibody half-life and complement fixation. Recently, M-protein light chain (LC) glycosylation has been shown to be associated with AL amyloidosis.

Hemolytic disease and reticulocytopenia of the newborn attributable to maternal immunoglobulin G anti-M reacting optimally at cold temperatures.

Background: Hemolytic disease of the fetus and newborn (HDFN) attributable to anti-M is rare, although case reports implicate anti-M in varying severities of HDFN, including fetal hydrops and intrauterine death.

Case Description: We describe the case of a newborn with HDFN associated with an atypical immunoglobulin (Ig) G anti-M that reacted best at cold temperatures. The maternal antibody detected in pregnancy was not reactive at 37°C, and a direct antiglobulin test (DAT) on red blood cells (RBCs) from the newborn was negative, suggesting an anti-M that should not have been clinically relevant.

Does Transfusion of Red Blood Cells Impact Germline Genetic Test Results?

Purpose: molecular testing is often indicated for recently transfused patients. However, there are no guidelines regarding the potential interference from donor DNA or whether it is necessary to wait for a period of time post-transfusion prior to genetic testing. While the majority of patients are transfused in the non-trauma setting using leukoreduced (LR) red blood cell products, the degree of leukoreduction varies among centers and is not universally practiced.

Implementation of a patient blood management program in hematopoietic stem cell transplantation (Editorial, p. 2763).

Background: Recipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood.

Study Design And Methods: This observational study assessed changes in blood product use and patient-centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center.

Seasonal variability is not observed in the rates of high anti-A and anti-B titers in plasma, apheresis platelet, and whole blood units tested by different methods.

Background: ABO-incompatible platelet transfusions are common, and transfusions with ABO-incompatible plasma are increasing with the use of group A plasma and group O whole blood (WB) in emergencies. Many centers screen blood products for anti-A and/or anti-B titers to help prevent hemolysis from ABO-incompatible transfusions, yet titer methods and definition of high titers are not standardized.

Study Design And Methods: This international multicenter study collected data on anti-A and anti-B titer practices for plasma, apheresis platelet (AP), and WB units from January 2015 through December 2017 to determine the prevalence of high-titer units using local definitions.

Extracorporeal Photopheresis Improves Survival in Hematopoietic Cell Transplant Patients with Bronchiolitis Obliterans Syndrome without Significantly Impacting Measured Pulmonary Functions.

We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study.

Does matching for SNPs in the MHC gamma block in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant improve outcomes?

Background: Matching at the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci is important in donor selection for patients undergoing unrelated allogeneic hematopoietic stem cell transplantation (ASCT). Additional matching across the MHC gamma region may further improve outcomes.

Methods: The MHC gamma region was retrospectively genotyped in 66 adult recipients of ASCT and their 10/10 matched unrelated donors.

Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant.

Objective: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution.

Measuring the impact of ambulatory red blood cell transfusion on home functional status: study protocol for a pilot randomized controlled trial.

Background: Red blood cell (RBC) transfusion is frequently employed in both ambulatory and hospital environments with the aim of improving patient functional status. In the ambulatory setting, this practice is particularly common in patients with malignancy due to anemia associated with their cancer therapy. Increasingly, the efficacy of this US$10.