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. When agglutination occurs ex vivo, complications with the collection and product may be encountered, resulting in adverse events or product loss. Here, we endeavor to share our experience in preventing and responding to known cases at risk of or spontaneous HPC agglutination in our human cell therapy laboratory. CASE REPORTS: Four cases of HPC products at risk for, or spontaneously, agglutinating were seen at our institution from 2018 to 2020. Planned modifications occurred, including ambient room temperature increases, tandem draw and return blood warmers, warm product transport and extended post-thaw warming occurred. In addition, unplanned modifications were undertaken, including warm HPC product processing and plasma replacement of the product when spontaneous agglutination of the product was identified. All recipients successfully engrafted after infusion. CONCLUSIONS: While uncommon, cold agglutination of HPC products can disrupt standard processes of collection and processing. Protocol modifications can circumvent adverse events for the donor and minimize product loss. Such process modifications should be considered in individuals with known risks for agglutination going to HPC donation/collection.

Thawed plasma (TP) as a substitute for intravenous immune globulin (IVIG) to prevent hypogammaglobulinemia post-therapeutic plasma exchange.

Intravenous immune globulin (IVIG) is a common treatment given after plasma exchange procedures to either prevent secondary hypogammaglobulinemia or as an adjunctive treatment for organ transplant rejection. However, side-effects are relatively common with this medication during and after infusion. This case-report describes our alternative to IVIG infusions post-plasma exchange. We hypothesize that in patients unable to tolerate IVIG, using thawed plasma as a replacement fluid provides a suitable increase in the patients post procedure immunoglobulin G (IgG) levels for patients with secondary hypogammaglobulinemia that are unable to tolerate IVIG infusions.

The first reported use of red blood cell exchange to treat hemoglobin Evans with secondary methemoglobinemia.

This manuscript describes a novel approach for treating patients with long-term sequelae from hemoglobin Evans (Hb Evans). After instituting conservative therapies for approximately 2 years, our patient's symptoms continually worsened. Therefore, we performed red blood cell exchange (RBCx) to reduce his Hb Evans percentage and his co-existing elevation of methemoglobin. Our assumptions of clinical benefit were based on our collective experience performing RBCx for patients with sickle cell disease. After the first exchange, pre- and post-laboratory results supported our approach and the patient experienced marked improvement in his clinical signs and symptoms. This report provides preliminary proof of principle for the use of RBCx to treat Hb Evans and other non-Hb S hemoglobinopathies.

How do I implement an outpatient program for the administration of convalescent plasma for COVID-19?

Convalescent plasma, collected from donors who have recovered from a pathogen of interest, has been used to treat infectious diseases, particularly in times of outbreak, when alternative therapies were unavailable. The COVID-19 pandemic revived interest in the use of convalescent plasma. Large observational studies and clinical trials that were executed during the pandemic provided insight into how to use convalescent plasma, whereby high levels of antibodies against the pathogen of interest and administration early within the time course of the disease are critical for optimal therapeutic effect. Several studies have shown outpatient administration of COVID-19 convalescent plasma (CCP) to be both safe and effective, preventing clinical progression in patients when administered within the first week of COVID-19. The United States Food and Drug Administration expanded its emergency use authorization (EUA) to allow for the administration of CCP in an outpatient setting in December 2021, at least for immunocompromised patients or those on immunosuppressive therapy. Outpatient transfusion of CCP and infusion of monoclonal antibody therapies for a highly transmissible infectious disease introduces nuanced challenges related to infection prevention. Drawing on our experiences with the clinical and research use of CCP, we describe the logistical considerations and workflow spanning procurement of qualified products, infrastructure, staffing, transfusion, and associated management of adverse events. The purpose of this description is to facilitate the efforts of others intent on establishing outpatient transfusion programs for CCP and other antibody-based therapies.

Implementation and 2-year outcomes of the first FDA-approved implantable apheresis vascular access device.

BACKGROUND: Patients requiring chronic apheresis treatments typically lack sufficient peripheral venous access to support long-term therapy. Historically, central venous tunneled catheters, septum-bearing subcutaneous ports, and fistulas were used to obtain required blood flow rates for apheresis procedures. In 2017, the US Food and Drug Administration approved the first intravascular device specifically designed for apheresis therapy, the PowerFlow Implantable Apheresis IV Port. METHODS: Several preimplementation meetings with key hospital stakeholders were held to determine the most efficient and safest strategy for integrating the PowerFlow device into our practice. Interventional radiologists implanted the apheresis port in patients meeting specified criteria. Performance metrics and adverse events were evaluated over a 2-year period, July 2017 through June 2019. RESULTS: Eighteen patients underwent apheresis therapy using the PowerFlow port. The most common apheresis therapy provided was extracorporeal photopheresis, followed by therapeutic plasma exchange and low-density lipoprotein apheresis. Flow rates up to 90 mL/min were obtained; the rates were limited by patient tolerance for the apheresis procedure. Complications included infection, obstruction due to fibroblastic sleeve, and migration of the vascular device. The estimated risk of PowerFlow-associated bloodstream infection in the study population was 0.18 per 1000 intravascular device days. CONCLUSION: The PowerFlow Implantable Apheresis IV Port can achieve flow rates necessary for all apheresis therapies and is a promising alternative vascular access device for patients undergoing apheresis.

New subcutaneous PowerFlow port results in cost and time-savings in a busy outpatient apheresis clinic.

Many vascular access options, such as subcutaneous ports, are currently on the market for use in both medication infusion and for procedures, such as therapeutic plasma exchange and extracorporeal photopheresis. We compared the cost and time necessary to complete apheresis procedures using either Angiodynamic's Vortex or Bard's PowerFlow subcutaneous ports by reviewing our experience on two patients undergoing long-term apheresis treatments with at least 10 procedures with each type of port. We analyzed the cost of needles and thrombolytic therapy, staff time, overall procedure length, and the total time the patient was in the apheresis unit. We also compared flow rates and alarm rates between the two ports. In this small pilot study, use of the PowerFlow port resulted in significant cost and time savings, with mixed results for flow rates. Our results need to be confirmed in a larger patient population prior to recommending wide implementation of Bard's PowerFlow port.

Iron deficiency anemia associated with extracorporeal photopheresis: A retrospective analysis.

BACKGROUND: Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS: We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS: A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%). CONCLUSIONS: Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients.

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. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non-ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV1 percentage predicted (FEV1PP) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV1PP before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non-ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, -9.5 versus -1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.

Vascular access considerations for extracorporeal photopheresis.

Extracorporeal photopheresis is an immunomodulatory therapy indicated for patients with cutaneous T-cell lymphoma, graft-versus-host disease, and heart or lung allograft rejection. Whole blood from the patient is drawn into the photopheresis instrument where it is separated into its components. Plasma, red blood cells, and the treated buffy coat are subsequently returned to the patient. Consistent, adequate blood flow is necessary to successfully complete the procedure. Vascular access options for photopheresis include peripheral vein cannulation, tunneled central venous catheters, and subcutaneous ports. Photopheresis is a very safe procedure; however, the complications and impact on the patient's quality of life associated with vascular access devices can be significant.

Rapid reduction of extremely high kappa free light chains in a patient with myeloma cast nephropathy.

This report describes a patient with light chain myeloma and acute renal injury. Serum kappa free light chain (FLC) was extremely elevated, >33,000 mg/dL. Treatment with therapeutic plasma exchange (TPE) started day 2 for biopsy-confirmed cast nephropathy. Bortezomib-containing chemotherapy was initiated on day 5, and hemodialysis for tumor lysis syndrome on day 7. TPE alone decreased kappa FLC >70% by day 5, indicating direct FLC removal was successful in this patient. A total of 25 TPE procedures were performed in a 31-day hospitalization. Hemodialysis was discontinued after 3 months, and the patient's renal function and kappa FLC remain stable. Although the use of TPE for FLC removal is controversial, recent evidence supports its use as adjuvant therapy for acute renal injury secondary to myeloma cast nephropathy. TPE can be effective for rapidly reducing FLC; however, several TPE procedures might be required to reduce the risk of hemodialysis dependency.

Increased troponin I is associated with fatal outcome in acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) has >90% mortality without therapeutic plasma exchange (TPE). Despite TPE, approximately 10% of patients still die, presumably from cardiac ischemia. We sought clinical or laboratory parameters associated with death by reviewing the records of all patients hospitalized with acquired TTP in our institution for 10 years, and collect demographics and results for hemoglobin, platelet count, creatinine, lactate dehydrogenase, transaminases, total bilirubin, creatinine kinase (CK), CK-MB, and troponin I. Sixty-eight patients were admitted 88 times, and 11 died. Survivors and non-survivors were similar in terms of sex, ethnicity, thrombocytopenia, and degree of anemia at presentation, while the latter were older, had worse renal function and higher CK, CK-MB, and troponin I (univariate analysis). However, only troponin I remained significant on multivariate analyses. We propose that patients with TTP should be monitored with troponin I to detect significant myocardial ischemia that could predict death despite TPE.

Extracorporeal photopheresis practice patterns: An international survey by the ASFA ECP subcommittee.

BACKGROUND: Although many apheresis centers offer extracorporeal photopheresis (ECP), little is known about current treatment practices. METHODS: An electronic survey was distributed to assess ECP practice internationally. RESULTS: Of 251 responses, 137 met criteria for analysis. Most respondents were from North America (80%). Nurses perform ECP at most centers (84%) and the majority of centers treat adults only (52%). Most centers treat fewer than 50 patients/year (83%) and perform fewer than 300 procedures/year (70%). Closed system devices (XTS and/or Cellex) are used to perform ECP at most centers (96%). The most common indications for ECP are acute/chronic skin graft versus host disease (89%) and cutaneous T-cell lymphoma (63%). The typical wait time for ECP treatment is less than 2 weeks (91%). Most centers do not routinely perform quality control assessment of the collected product (66%). There are device-specific differences in treatment parameters. For example, XTS users more frequently have a minimum weight limit (P = 0.003) and use laboratory parameters to determine eligibility for treatment (P = 0.03). Regardless of device used, the majority of centers assess the clinical status of the patient before each procedure. Greater than 50% of respondents would defer treatment for hemodynamic instability due to active sepsis or heart failure, positive blood culture in the past 24 h or current fever. CONCLUSION: This survey based study describes current ECP practices. Further research to provide evidence for optimal standardization of patient qualifications, procedure parameters and product quality assessment is recommended.

Carfilzomib: A cause of drug associated thrombotic microangiopathy.

Carfilzomib is a selective proteosome inhibitor approved for treatment of relapsed and refractory multiple myeloma. Recent reports have linked exposure to carfilzomib with development of thrombotic microangiopathy (TMA). We describe two cases of biopsy proven thrombotic microangiopathy that occurred after the initiation of carfilzomib (dosed at 32 mg/m(2) and 23 mg/m(2), respectively) for relapsed multiple myeloma. Both patients were managed with discontinuation of the drug, therapeutic plasma exchange (TPE) and supportive care. Hemoglobin, platelets and renal function did not improve with TPE. TMA resolved with creatinine returning to baseline several weeks after discontinuation of the drug. The outcomes suggest that TPE is not beneficial for treating carfilzomib-induced TMA.

Establishing an institutional therapeutic apheresis registry.

Apheresis was first performed as a therapeutic procedure in the 1950s. The first national therapeutic apheresis (TA) registry was established in Canada in 1981 and other national registries followed, including two attempts at establishing an international TA registry. There is no national registry in the United States. Our large, academic, tertiary hospital has a very active TA service. We created a TA database to track all procedures performed by the apheresis service by transferring data from paper appointment logs and the electronic medical records into a Microsoft Access database. Retrospective data from each TA procedure performed at UAB from January 1, 2003 through December 31, 2012 were entered, including the type of procedure, indication, date, and patient demographics. Microsoft Excel was used for data analysis. During the 10-year period, our TA service treated 1,060 patients and performed 11,718 procedures. Of these patients, 70% received therapeutic plasma exchange (TPE), 21% received extracorporeal photopheresis (ECP), 4.5% received red cell exchange (RCE), 4.2% received leukocytapheresis, and 0.6% underwent platelet depletion. Among the procedures, 54% were TPEs, 44% were ECPs, 1.3% were RCEs, 0.5% were leukocytaphereses, and 0.1% were platelet depletions. According to the current literature, national and international TA use is underreported. We believe that the UAB TA registry provides useful information about TA practices in our region and can serve as a model for other institutions. Furthermore, data from multiple institutional registries can be used for clinical research to increase the available evidence for the role of TA in various conditions. J. Clin. Apheresis 31:516-522, 2016. © 2015 Wiley Periodicals, Inc.

Extracorporeal photopheresis for the treatment of autoimmune diseases.

The immune system is tasked with the unique challenge of recognizing foreign pathogens and damaged cells while at the same time preserving and protecting the integrity of "self". When this process fails, severe consequences including cancer and autoimmunity are the end result. Current therapies aimed at treating autoimmune disorders result in generalized immunosuppression and place the patient at increased risk for infection and malignancy. ECP is a potential therapeutic intervention that recapitulates natural physiologic processes of tolerance induction to restore immune homeostasis. Several clinical trials suggest that ECP may be used to treat a broad spectrum of autoimmune diseases.

Extracorporeal photopheresis: technique, established and novel indications.

Extracorporeal photopheresis (ECP) has had a major impact in the treatment of various conditions in the past 25 years. Although it was initially developed for the treatment of patients with resistant cutaneous T cell lymphoma (CTCL), this therapy was later used to treat recipients of solid organs and stem cell transplants with rejection or graft-versus-host disease (GVHD), respectively. A significant number of patients with CTCL can achieve long term remission with ECP therapy. Those patients with heart or lung transplants may experience fewer or shorter rejection episodes following ECP. Furthermore, patients that respond to ECP can generally reduce the dose of immunosuppression medication, thus minimizing the morbidity caused by drugs such as corticosteroids and calcineurin inhibitors. While the exact mechanism of action of ECP is not well-understood, evidence suggests that reinfusion of the patient's apoptotic white blood cells, the ultimate product of ECP, promotes immunomodulatory events that are beneficial in patients with CTCL, transplant rejection, GVHD, and possibly other inflammatory conditions.

Therapeutic plasma exchange rapidly improves cardiac allograft function in patients with presumed antibody-mediated rejection.

BACKGROUND: Allograft dysfunction due to presumed antibody-mediated rejection (pAMR) is one of the most serious complications of heart transplantation. Combination therapies of high-dose steroids, intravenous immune globulin, and/or therapeutic plasma exchange (TPE) are often used in this setting. METHODS: We performed a 9-year retrospective review of all episodes of pAMR treated with TPE at our institution. pAMR diagnosis was based on clinical and pathologic findings. Left ventricular ejection fraction (LVEF) was measured at baseline, prior to initiation of TPE, and during the course of treatment. RESULTS: There were 42 patients with 47 episodes of pAMR treated with TPE. The majority of episodes were treated with three TPE; however, eight required only two TPE and five episodes required >3 TPE. All episodes of pAMR had LVEF measured before and after the series of TPEs. The mean pre-TPE LVEF was 38% compared with a post-therapy mean LVEF of 50% (P < 0.0001). In 16 episodes of pAMR, for which LVEF was measured following each apheresis, there was significant improvement of allograft function after the first TPE (pre-TPE mean LVEF of 31% and post-first TPE mean LVEF of 37%; P = 0.02). Incremental and significant improvement in allograft function continued following each TPE. Changes in human leukocyte antigen-donor specific antibodies and fibrinogen did not correlate with ejection fraction response. CONCLUSIONS: The rapid improvement in allograft function in our patients is most likely due to TPE as other pharmacologic interventions have longer onset. TPE should be considered a first-line intervention in the setting of pAMR.

Peering into the future: hepcidin testing.

Hepcidin, a small 25 amino acid peptide, has been well established as the iron regulatory hormone. Its expression is upregulated in response to iron and inflammatory cytokines, and downregulated in anemic or hypoxic states. Hepcidin decreases iron export into the plasma by binding to and inducing the degradation of ferroportin, an iron channel located on macrophages and the basolateral surface of enterocytes. This leads to decreased absorption of parental iron by the enterocytes, reduced recycling of erythrocyte iron by macrophages, and increased iron stores in the hepatocytes. Although hepcidin assays are not currently approved for clinical use in the United States, there is much interest in the potential use of this biomarker for management of iron related medical conditions. This review briefly summarizes the current hepcidin test platforms under investigation and the challenges associated with development of a clinical assay for this biomarker. In addition, selected potential future applications hepcidin testing in the clinical setting are addressed.