Transfusion-associated Graft-versus-host Disease Research Articles

X-ray irradiation effectively inactivated lymphocytes in transfusion in vivo monitored by the bioluminescence transfusion-associated graft-versus-host disease model.

Transfusion of cold-stored whole blood is the preferred resuscitation method for trauma patients but may cause transfusion-associated graft-versus-host disease (TA-GVHD). Standard clinical practice to prevent this is to irradiate blood components with gamma-rays. X-ray irradiations are also a safe and effective alternative to gamma-ray irradiation. We established a visual mouse model of TA-GVHD to compare the viability and function of lymphocytes exposed to gamma- and x-ray irradiation. A haploidentical transplantation mouse model was established to simulate TA-GVHD with Balb/c mice as donors and hybrid F1 CB6 mice (Balb/c × C57) as recipients. Spleen cells from Tg-Fluc+ Balb/c mice were isolated and irradiated with gamma-rays and x-rays. Lymphocyte activation, apoptosis and proliferation post phorbol 1 2-myristate 1 3-acetate (PMA) stimulation were evaluated. After transfusion, we monitored Fluc+ lymphocytes daily by bioluminescence imaging. Recipients were euthanized on day 21, and tissues were examined pathologically and for inflammatory cytokines. The viability of gamma- or x-ray irradiated lymphocytes decreased significantly with slight changes in proliferation in vivo after transfusion. Compared with the non-irradiated group, both the gamma- and x-ray irradiated groups showed significantly decreased clinical scoring and inflammatory cytokine levels. The fluorescence intensity of the body and target organs was reduced after irradiation. No recipients acquired TA-GVHD after lymphocyte transfusion subjected to gamma- or x-rays, showing that x-rays inactivate as well as gamma rays and are suitable for irradiating whole blood.

Transfusion-Associated Graft-Versus-Host Disease in Adults.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but fatal complication of blood transfusion that usually develops two to 30 days following a blood transfusion giving rise to graft versus host disease (GVHD) clinical features that are consisting of fever, skin rash, jaundice, diarrhea, and pancytopenia. The disease is fulminant in most patients with a mortality rate of >90% of cases. The main aim of this review is to enhance awareness among medical practitioners about this fatal disease. Data were extracted manually from the main medical databases (Medline, Scopus, and Google Scholar) after the revision of selected articles and assessed for their contribution to the knowledge of TA-GVHD. TA-GVHD occurs when the viable donor T-cells in the blood or blood products attack the recipient's tissues which his/her immune system is incapable to destroy due to several reasons. The recipient's tissues that are usually involved in TA-GVHD include the liver, intestine, skin, lungs, and bone marrow. Any blood component either whole blood, packed red blood cells (RBCs), platelets, or fresh non-frozen plasma that contains viable T lymphocytes can cause TA-GVHD. Host immunodeficiency, transfusion of fresh blood, and partial human leukocyte antigen (HLA) matching between the donors and the recipients represent the major risk factors of TA-GVHD. Partial HLA matching includes immunocompetent recipients who receive blood from a first-degree relative also, seen in genetically homogenous populations because of high rates of consanguineous marriage. The diagnosis of TA-GVHD is mainly suspected based on clinical manifestations. However, a histopathological study of either skin or rectal biopsy is diagnostic. The treatment of TA-GVHD is generally not effective, unless the patient received emergency stem cell transplantation, while prevention via irradiation of blood or blood products represents the standard of care for this disease. In conclusion, medical practitioners should have a high index of suspicion for this disease. Moreover, future clinical trials targeting and comparing the outcomes of the different therapeutic options for TA-GVHD are required.

Transfusion reaction: A blind spot in autopsy

Although blood transfusion is generally safe, there are adverse events with varying severity even that can lead to death including Acute Haemolytic Transfusion Reaction (AHTR), anaphylaxis, bacterial sepsis, Transfusion Related Acute Lung Injury (TRALI) and Transfusion Associated Circulatory Overload (TACO). Transfusion Associated Graft vs Host Disease (TAGVHD) is a delayed type of reaction that can lead to death. Ascertaining the cause of death is complicated in such situations and multidisciplinary investigations are needed.Serological investigations should be performed in the transfusion laboratory to detect haemolysis, immunological incompatibility, and bacterial contamination. In the postmortem examination AHTR can be diagnosed with serological investigations and presence of incompatible red cells can be identified in postmortem tissue samples by immune-histochemical methods. Detection of HLA antibodies in the respiratory tract tissues and intended donor investigations can confirm the diagnosis of TRALI. In a case of suspected bacterial contamination isolation of same organism in the postmortem blood and in the intended pack can conclude the diagnosis. In anaphylaxis, inflammation of the respiratory tract with eosinophilia can be seen and measuring the serum tryptase level is useful. In TAGVHD host tissue necrosis and lymphocyte infiltration are +seen and that can be confirmed by showing the DNA chimerism by PCR analysis.Further studies are recommended to establish protocols and guidelines for postmortem examination following a transfusion reaction.

Absorbed dose evaluation of a blood irradiator with alanine, TLD-100 and ionization chamber

Irradiation of blood bags using X-ray irradiators and dosimetry services are required to ensure uniform dose levels in the range 25–50 Gy to prevent Transfusion Associated Graft versus Host Disease (TA-GvHD). An absorbed dose characterization of a Raycell MK2 X-Irradiator was performed using three different dosimetric systems. Results showed a dosimetric accuracy of the ionization chamber together with the Alanine dosimeter. TLDs measurements exhibited a small overestimation by 4% of the absorbed dose. The Dose Uniformity Ratio (DUR), between maximum and minimum dose levels in the canister, was in good agreement with the manufacturer specifications (≤1.5).

DOSE MAP BLOOD IRRADIATOR DOSIMETRY SYSTEM: CUSTOMIZED BLOOD EQUIVALENT PHANTOM AND GAFCHROMIC EBT-XD FILM

Blood irradiation is done to sterilize and cease donor T-lymphocytes functionality to avoid Transfusion Associated-Graft Versus Host Disease (TA-GVHD). Dose mapping is the primary means of ensuring that the irradiation process is being conducted correctly. The aim of this study is to measure the minimum, maximum and central absorbed gamma radiation dose delivered at the newly customized blood equivalent phantom using a Gafchromic EBT-XD film. A Gammacell 3000 Elan Blood Irradiator with Cesium-137 source was used. To obtain the dose calibration curves, the films were placed at the center of a phantom and irradiated with the dose range from 5 Gy to 35 Gy with one unirradiated film as a control. The dose calibration curve was plotted using red, green and blue channels. While, for the dose mapping measurement, the irradiation exposure of 9.03 minutes was used to deliver a central dose of 25 Gy to the film. The response of the film will be compared with the GC Dose Mapping Report 2022 which used a water equivalent medium as a phantom. For the calibration curve, the red channel of the film was utilized in this study as it had a higher signal than the other channel. The doses obtained at central, minimum and maximum using EBT-XD film with customized blood equivalent phantom were in agreement with that obtained from GC Dose Mapping Report 2022 to be within ±7.6%, ±8.51% and ±9.95% respectively. We concluded that the customized blood equivalent phantom together with EBT-XD film has a potential to map the dose in blood irradiator accurately. The doses obtained from EBT-XD film were in the range of doses needed to inhibit the proliferation of the T-lymphocytes with central, minimum and maximum doses were 26.9 Gy, 17.2 Gy and 35.7 Gy respectively.

Battle of the (Chat)Bots: Comparing Large Language Models to Practice Guidelines for Transfusion-Associated Graft-Versus-Host Disease Prevention.

Published guidelines and clinical practices vary when defining indications for irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). This study assessed irradiation indication lists generated by multiple artificial intelligence (AI) programs, or chatbots, and compared them to 2020 British Society for Haematology (BSH) practice guidelines. Four chatbots (ChatGPT-3.5, ChatGPT-4, Bard, and Bing Chat) were prompted to list the indications for irradiation to prevent TA-GVHD. Responses were graded for concordance with BSH guidelines. Chatbot response length, discrepancies, and omissions were noted. Chatbot responses differed, but all were relevant, short in length, generally more concordant than discordant with BSH guidelines, and roughly complete. They lacked several indications listed in BSH guidelines and notably differed in their irradiation eligibility criteria for fetuses and neonates. The chatbots variably listed erroneous indications for TA-GVHD prevention, such as patients receiving blood from a donor who is of a different race or ethnicity. This study demonstrates the potential use of generative AI for transfusion medicine and hematology topics but underscores the risk of chatbot medical misinformation. Further study of risk factors for TA-GVHD, as well as the applications of chatbots in transfusion medicine and hematology, is warranted.

EVALUATION OF POSSIBLE COMPLICATIONS OF IRRADIATION OF BLOOD PRODUCTS ON PATIENTS

Background: Blood transfusion is a life-saving but high-risk procedure in various medical conditions as it is not a simple fluid infusion but an organ transplant. Although blood transfusions save lives, they may cause serious, life-threatening reactions. Nowadays, the number of reactions has decreased significantly with the reduction of leucocyte content of blood products or their irradiation. 
 Materials and Method: A total of 5582 patients who received irradiated blood products in our hospital between 14/08/2020 and 17/02/2023 were included in the present study. Erythrocyte suspension, platelet apheresis, and pooled platelet suspension were irradiated at doses of 25–30 Gy.
 Results: A total of 5582 blood products including 4990 erythrocyte suspensions, 282 pooled platelet suspensions, and 310 platelet apheresis were irradiated in the present study. No transfusion-associated Graft Versus Host Disease was identified in any patient included in the present study and there were only mild allergic reactions and febrile non-hemolytic transfusion reactions. 
 Conclusions: Based on the data obtained here from, it was concluded that irradiation of blood products can prevent the highly fatal transfusion-related Graft Versus Host Disease.

An Overview of the Identification, Prevention, and Management of Immunological Reactions to Blood Transfusion

lood transfusions are prevalent treatment procedures nowadays for various medical conditions that involve the administration of whole blood or separated blood components alone or in various combinations that can be administered intravenously; these are undertaken with therapeutic or curative goals in mind, they may carry associated risks and complications that must be weighed against the benefits before initiating therapy. A typical subset of complications associated with transfusions includes Transfusion reactions. These include Non-infectious (Acute and Delayed) and infectious complications. Non-infectious transfusion reactions include Immune-mediated reactions to blood components, such as Febrile Non-hemolytic Transfusion reactions (FNHTR), Allergic Transfusion reactions, Hemolytic Transfusion reactions (HTR), Transfusion-related Acute Lung Injury (TRALI), and Transfusion Associated Graft versus Host Disease (TAGVHD), these reactions have different mechanism and complications between them. They can be differentiated for the mechanism of action, presentation time, and clinic. Blood transfusion immunological reactions remain a significant concern in clinical settings, leading to various symptoms. Diagnosing these reactions requires careful monitoring and evaluation of the patient’s clinical status and laboratory parameters. The prevention methods for these reactions include pre-transfusion testing, selecting appropriate blood products, and using leukoreduced blood products. Treatment options may include supportive care, discontinuation of transfusion, and immunosuppressive therapy in severe cases. This article aims to provide an overview of how to identify immune-mediated transfusion reactions, manage them as they occur, and even prevent them if possible.

Understanding and management of adverse transfusion reactions

Blood transfusion is an essential supportive treatment in modern medicine and is frequently used. Acute hemolytic transfusion reaction is prevented by conducting a cross-matching test; however, nonhemolytic transfusion reactions are difficult to predict. Furthermore, adverse transfusion reactions are not sufficiently recognized by healthcare workers because they rarely occur, except for urticaria and febrile reactions. Thus, further awareness of adverse reactions, particularly regarding transfusion-associated circulatory overload, is needed. Since the introduction of irradiated blood, no transfusion-associated graft-versus-host-disease (TA-GVHD) case has been reported for over 20 years. However, education on the risk of TA-GVHD is important in facilities where nonirradiated blood is supplied or in situations such as unavoidable in-house blood collection on remote islands. The incidence of transfusion-transmitted hepatitis was significantly decreased by the introduction of nucleic acid amplification tests. Recently, the Japanese Red Cross Society is focusing on the reduction of transfusion-associated bacterial infections, which are rare but serious complications. This review provides an updated overview of adverse transfusion reactions and their management measures. Understanding adverse transfusion reactions will enable healthcare workers to recognize symptoms and take prompt action.

Adverse reactions following transfusion of blood components, with a focus on some rare reactions: Reports to the International Haemovigilance Network Database (ISTARE) in 2012-2016.

The International Haemovigilance Network's (IHN) ISTARE database collects surveillance data on all adverse reactions (AR) associated with transfusion of blood and blood components, facilitating the sharing of best practice and benchmarking for improving blood safety and quality. Up to 2012, no publications discussed certain rare AR. The aim of this study is to examine ISTARE data on AR from 2012 to 2016, focusing on hypotensive reactions, post-transfusion purpura (PTP), transfusion-associated graft versus host disease (TA-GvHD), hyperkalemia and hypocalcemia. National Haemovigilance Systems (HVS), provided aggregate annual data on AR by type of reaction, severity, imputability to transfusion, and blood component implicated. Twenty-nine HVS provided 104 annual reports covering 107,778,290 blood units issued. Among AR reported, 25% were serious, including 368 deaths. The 284 transfusion-transmitted infections included 187 bacterial infections, 84 viral and 13 parasitic or fungal; nine deaths resulted. AR related to the respiratory system transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnoea accounted for 8.3% of all AR, 20.1% of serious, and 52.2% of deaths. Of 1634 rare AR, 1565 were hypotensive, 38 PTP, 17 GvHD, 9 hyperkalemia and 5 hypercalcemia. Half were serious and 16 fatalities were recorded (13 hypotensive, 2 GvHD, one PTP). Among 14 countries that reported any hypotensive AR, incidences diverged widely. ARs in this group are frequently severe or life-threatening. Hypotensive AR are the most common, but may have been overlooked and counted under allergic and other AR presenting with hypotension. Compliance with the ISBT definition may be suboptimal, thus its real incidence may be higher. Data on GvHD may contribute to clarifying the role of leukodepletion with or without irradiation. ISTARE continues to be a useful surveillance tool for all transfusion AR and provides relevant insights into overlooked and rare AR, thus offering important contributions towards maximising transfusion safety.

Gamma and X-ray irradiation do not affect the in vitro quality of refrigerated apheresis platelets in platelet additive solution (PAS-E).

Platelet refrigeration (cold storage) provides the advantages of an extended shelf life and reduces the risk of bacterial growth, compared to platelets stored at room temperature (RT). However, processing modifications, such as irradiation, may further improve the safety and/or alter the quality of cold-stored platelets. Platelet components are irradiated to prevent transfusion-associated graft versus host disease (TA-GvHD) in high-risk patients; and while irradiation has little effect on the quality of RT-stored platelet components, there is no data assessing the effect irradiation has following cold storage. Triple-dose apheresis platelets were collected in 40% plasma/60% PAS-E, using the TRIMA apheresis platform, and refrigerated (2-6°C) within 8h of collection. On day 2, one of each component was gamma or X-ray irradiated or remained non-irradiated. Platelets were tested over 21 days. The platelet concentration decreased by approximately 20% in all groups during 21 days of storage (p > .05). Irradiation (gamma or X-ray) did not affect platelet metabolism, and the pH was maintained above the minimum specification (>6.4) for 21 days. The surface phenotype and the composition of the supernatant was similar in non-irradiated and irradiated platelets, regardless of the source of radiation. Functional responses (aggregation and clot formation) were not affected by irradiation. Gamma and X-ray irradiation do not affect the in vitro quality of platelet components stored in the cold for up to 21 days. This demonstrates the acceptability of irradiating cold-stored platelets, which has the potential to improve their safety for at-risk patient cohorts.

Modified irradiation technique for transfusable blood using a clinical linear accelerator

Whole blood irradiation prior to blood transfusion mitigates the risk of Transfusion Associated Graft versus Host Disease (TA-GvHD) to the receiver. This study aimed to improve dose homogeneity, also to benefit from a faster technique and a simplified blood irradiation workflow. An acrylic box accommodating eight units of blood has been fabricated, build-up material being used to ensure dose homogeneity. A linear accelerator dose distribution treatment plan for blood bag irradiations has been evaluated, measurement of dose using nanoDot optically stimulated luminescent dosimeters (OSLD) allowing comparison with calculated dose. By using build-up material, dose distribution was within 95%–107% of the prescribed dose. With all eight units of blood accommodated in the box, an irradiation time of 20 min per box has been needed. Compared to a previously adopted procedure, use of the acrylic box and build-up material maintains dose homogeneity, also simplifying the workflow, the technique also being easy to undertake by the operators.

Use of X-rays to prevent transfusion-induced graft-versus-host disease

Transfusion associated graft versus host disease (TA-GvHD) is a rare complication of transfusion treatment with blood products containing viable lymphocytes. The risk of developing TA-GvHD depends on number and sustainability of lymphocytes in blood product, host’s immune system reactivity and the difference in human leukocyte antigen (HLA) system between donor and recipient. Standard method of TA-GvHD prevention is irradiation of blood products with ionizing radiation and absorbed dose of 25-50 Gy. The aim of irradiation is inactivation of viable lymphocytes in blood product containing cells (red blood cells, platelets, granulocytes) and lymphocyte proliferation inhibition in blood product recipient. In the last two decades, gamma irradiation has been extensively abandoned and replaced with specially designed cabinet machines using X-ray irradiation which are suitable for hospital and blood bank use. This reduces the risk of accidental or deliberate misuse of radioactive source, solves radioactive waste disposal issues and reduces ionizing irradiation exposure of employees in blood establishments. In Blood Bank of Croatian Institute of Transfusion Medicine, X-ray irradiation of blood products has been carried out since 2014 with a year rate of 20,000 irradiated cell blood products used in treatment of patients at risk of developing TA-GvHD.

Is pathogen reduction an acceptable alternative to irradiation for risk mitigation of transfusion-associated graft versus host disease?

Transfusion-associated graft versus host disease (TA-GVHD) is a highly morbid and often fatal adverse event associated with transfusion of cellular blood products [platelets, red blood cells (RBCs) and whole blood] and more rarely with never-frozen plasma products. It is caused by residual viable donor T-lymphocytes that proliferate and actively target recipient tissues. Selective or universal irradiation of blood components using gamma-irradiation and more recently, X-ray irradiation, are the most commonly applied interventions and have been validated by the demonstration of in vitro T-lymphocyte inactivation, in murine models of TA-GVHD and by years of clinical experience. Irradiation, however, has multiple limitations including a sharp dose-response curve that renders quality control of dosage critically important, the use of radioactive radiation sources that are a terrorism risk, and selective implementation in many countries that leads to inadvertent omission and patient risk exposure. Certain pathogen reduction technologies (PRT) for platelets have been approved by regulatory authorities and endorsed by professional societies as an alternative to irradiation for reducing the risk of TA-GVHD, and PRT for RBCs and whole blood are in development. While the mechanism of action of T-lymphocyte inactivation differs from gamma/X-ray irradiation, the impact on T-lymphocyte inactivation for PRT is equivalent or superior to that of irradiation as demonstrated by sensitive in vitro lymphocyte proliferation assays and in vivo mouse models that approximate human TA-GVHD. Clinical trials and cumulative routine-use experience attest to the efficacy of PRT when used as an alternative to irradiation. While T-lymphocyte inactivation efficacy varies between PRT platforms, the implementation of PRT for platelets increases blood safety for patients beyond the mitigation of TA-GVHD, by decreasing the risk of transfusion transmitted infections with known viruses, bacteria and parasites as well as emerging pathogens.

Can maternofetal transfusion provoke adverse outcomes akin to TA-GVHD?

During pregnancy, a bidirectional transfer of molecules and cells takes place through the placenta, which can be considered a transfusion. For decades, we have wondered whether said transfusion can lead to a true TA-GVHD. We propose several factors that may influence production of TA-GVHD during pregnancy. In order to achieve this, we shall take into account possible destinations for transfused leukocytes, which represent extremely different scenarios and may include transfusion associated-graft versus host disease (TA-GVHD).

Can transfusion-associated graft-versus-host disease (TA-GvHD) be prevented with leukoreduction alone?

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare but devastating disease with a very high mortality rate. Because of the high mortality and lack of effective treatments, the current state of the art is aimed at preventing TA-GvHD and this can be accomplished via irradiation of all cellular blood products (red blood cells, granulocytes, and platelets). However, given that TA-GvHD is driven by contaminating white blood cells, and the fact that the international transfusion community has largely embraced leukoreduction, this raises the question as to whether the quantitative reduction of leukocytes via filtration can itself prevent TA-GvHD, thus allowing hospitals to skip irradiation steps? In this paper, we review the medical literature to determine how many leukocytes are needed to be removed to prevent TA-GvHD, while providing brief overviews of this entity itself and current irradiation strategies.

Transfusion-associated graft-versus-host disease, transfusion-associated hyperkalemia, and potassium filtration: advancing safety and sufficiency of the blood supply

Irradiation of cellular blood components is well established as a countermeasure against transfusion-associated graft-versus-host disease (TA-GVHD). Unintended consequences of ionizing radiation are also well established. The red cell “storage lesion” – a progression of metabolic, functional, and morphological changes – may be exacerbated by irradiation rates and doses typically used for TA-GVHD prophylaxis. With or without irradiation, a storage lesion change of clinical concern is the accelerated egress of intracellular potassium. ATP depletion during storage limits the activity of the red cell membrane’s sodium-potassium pump (Na,K-ATPase), which normally maintains intracellular potassium (K+) at levels 30–40 times higher than the extracellular milieu. The natural diffusion of potassium down this concentration gradient proceeds faster if the cell membrane is damaged, and oxidative damage to cellular membranes and membrane proteins – including Na,K-ATPase – is an effect of ionizing radiation.Preventing transfusion-related hyperkalemia is a reason for limiting the shelf life of irradiated red cells. In the absence of specific measurements to assess storage lesion in a particular unit of blood, and in the absence of specific interventions at the time of transfusion to mitigate effects of storage lesion, it is consistent with the precautionary principle to put conservative limits on a blood component’s shelf life. On the other hand, both the safety and sufficiency of a nation’s blood supply might be improved by interventions that benefit specific recipients when they are transfused, and benefit future patients by extending the allowable shelf life of blood components. Potassium filtration of irradiated red blood cell components is one such intervention.

How is transfusion-associated graft-versus-host disease similar to, yet different from, organ transplantation-associated graft-versus-host disease?

Graft-versus-host disease (GVHD) is a rare, usually fatal complication following blood transfusion or organ transplantation, namely transfusion-associated GVHD (TA-GVHD) and organ transplantation-associated GVHD (OA-GVHD). The dominant mechanism of GVHD is exposure to viable donor lymphocytes that are not recognized as foreign by, but able to respond to, the recipient. The clinical features and relative risk factors of either TA-GVHD or OA-GVHD are yet to be fully understood. The current review article aims to discuss and summarize the similarities and differences between TA-GVHD and OA-GVHD to gain a deeper understanding of the pathogenesis.It is evident that the shared human leukocyte antigens (HLA) between donor and recipient and immunocompromised status of the recipient are the two main risk factors for the development of both TA-GVHD and OA-GVHD. In particular, the homozygous donor with donor-dominant one-way matching at the three loci HLA-A, -B, and -DR has a high risk of developing GVHD following liver transplantation, and such donors should be excluded to prevent it. However, the development of GVHD is thought to be related to a combination of several risk factors, and the contribution of each risk factor remains unknown. Further studies are warranted to determine the important contributing factors that lead to an accurate prediction of GVHD development.

The timing of gamma irradiation and its effect on cell-free and microvesicle-bound hemoglobin. The BEST collaborative study.

Gamma irradiation of red cell concentrates (RCCs) is regularly used to prevent transfusion-associated graft-versus-host disease (TA-GvHD) in at-risk patients. While studies have indicated that irradiated RCCs exhibit increased hemolysis, there have been no efforts to differentiate between free- and microvesicle (MV)-bound hemoglobin (Hb). As an increase in the proportion of free-Hb in irradiated RCCs could alter vascular function, we sought to characterize differences in the state of extracellular Hb based on the timing of irradiation. Four separate pools of seven CPD/SAGM leukoreduced RCCs were produced and split into four sets of seven identical units. The units from each set were subject to irradiation (25 Gy) at six different points during storage, with one unit serving as a nonirradiated control. All testing was performed immediately following unit expiry on day 43. The earlier in storage that units were irradiated, the higher the hemolysis and the lower the proportion of MV-bound Hb. Units irradiated earlier in storage (1-8 days post collection) additionally had lower membrane rigidity (KEI ), lower mean corpuscular Hb concentrations (MCHC), and higher mean corpuscular fragility (MCF). Morphology indices, mean cell volume (MCV), mean corpuscular Hb (MCH), phosphatidylserine (PS) expression, as well as MV production and size did not however differ significantly between groups based on the timing of irradiation. Our findings indicate that irradiation timing can alter the state of extracellular Hb, with "early" irradiation promoting an increased proportion of cell-free Hb as well as mechanical damage to the RBC membrane.

Impact of Platelet Transfusion on Pulmonary Function of Hematology Oncology Patients: The Piper Study

Background. Platelet transfusion is a critical therapy for hematology-oncology patients at risk of transfusion-transmitted infection (TTI) and pulmonary injury. Amotosalen-UVA pathogen reduction (PR) treatment of apheresis platelet components (PC) in plasma or additive solution (INTERCEPT Blood System for Platelets, Cerus, Concord, CA) is FDA approved to reduce risk of TTI and transfusion associated graft vs. host disease (TA-GVHD). PRPC meet the FDA bacteria risk reduction guidance, and approximately 50% of U.S. PC are PRPC. Amotosalen-UVA PR replaces bacteria screening, gamma irradiation, and CMV serology. PR is performed within 24 hours of collection enabling early release of PRPC with 5-day storage. We tested the hypothesis that PRPC were not inferior to conventional PC(CPC) for the incidence of pulmonary injury. Methods. An open-label sequential cohort study in platelet transfusion dependent hematology-oncology patients was conducted under routine practice conditions in 15 clinical centers. Each site enrolled a CPC cohort followed by a PRPC cohort using 4 primary therapy strata matched ± 10%: chemotherapy without hematopoietic cell transplant (HCT), HCT with myeloablation, HCT with non-myeloablative conditioning, and HCT with reduced intensity conditioning (RIC). Patients were supported with the assigned PC type for up to 21 days with 7 days of surveillance after the last PC exposure. Patients participated in only one cohort. The primary endpoint was treatment emergent assisted mechanical ventilation (TEAMV) by intubation or tight mask with positive end expiration pressure (5cm H 2O) after initiation of study PC. All endpoint patients were adjudicated by a blinded pulmonary expert panel (PEP) for diagnosis of acute respiratory distress syndrome (ARDS) by the Berlin Criteria. Secondary endpoints included: time to initiation of TEAMV, clinically significant pulmonary adverse events (CSPAE, CTCAE ≥ Grade 2), transfusion reactions, and mortality. The incidence of TEAMV by non-inferiority (margin = 2.3%), and secondary endpoints were analyzed by modified intention to treat (mITT) and per protocol (PP). Sensitivity analyses with propensity score matching for key variables were conducted for the primary endpoint. The associations between PC and categorical variables were tested by stratified Cochran-Mantel-Haenszel and continuous variables by ANOVA for two-sided significance p = 0.05. results. A total of 2291 pediatric and adult patients (1068 PRPC and 1223 CPC) were enrolled in the respective cohorts with transfusion of 5,277 PRPC and 5,491 CPC. PC assignment compliance and study completion were > 94%. For the mITT data set, the cumulative incidence of TEAMV was lower for the PRPC cohort (log rank p = 0.039) than the CPC cohort (2.9% versus 4.6%, HR = 0.633: 95% CI 0.408-0.982). PRPC by mITT were non-inferior to CPC for the incidence of TEAMV due to all indications, and for TEAMV with pulmonary dysfunction (PD) by PEP (Table). PP analyses were consistent with mITT. Relative risk (RR) of TEAMV showed significantly (p<0.05) decreased RR of PRPC respectively for baseline covariates: age < 65 (0.53), male (0.54), non-white (0.32), chemotherapy (0.40), prior pulmonary disease (0.55), and prior cardiac disease (0.58). Least squares (LS) mean days to initiation of TEAMV for patients with PD were longer for PRPC recipients. PEP adjudicated incidence of ARDS was not significantly different between cohorts (Table). Total and serious CSPAE were not different between the cohorts. There were no significant differences between cohorts in Respiratory, Thoracic, and Mediastinal Disorders, the most frequent system organ class event. Mortality was not different between cohorts. Multivariate analysis (mITT) for the probability of CSPAE or transfusion associated cardiac overload (TACO) showed PC type had no effect. The odds ratio (OR) of CSPAE or TACO during PC support was significantly increased (p< 0.05) in both cohorts for history of cardiac disease (1.35), history of pulmonary disease (2.57), diagnosis of Myelodysplasia (1.88), and diagnosis of Myelodysplasia/Myeloproliferative disease (2.27). There was a significant treatment interaction (p= 0.043) between PC type and acute myelogenous leukemia (AML), increased OR = 1.49 for CPC versus PRPC. Conclusions. PRPC did not potentiate pulmonary injury during PC support; and their use may decrease TEAMV risk with benefit of reduced TTI risk. [Display omitted] DisclosuresWheeler: Novo Nordisk A/S: Consultancy; Bayer: Consultancy; BioMarin: Consultancy; HEMA Biologics: Consultancy; Spark: Consultancy; Takeda: Consultancy; UniQure: Consultancy. Nooka: Janssen Oncology: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Oncopeptides: Consultancy; Amgen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Adaptive technologies: Consultancy; GlaxoSmithKline: Consultancy, Other: Travel expenses; Karyopharm Therapeutics: Consultancy. Uhl: UpToDate: Patents & Royalties; Abbott: Consultancy, Speakers Bureau; Grifols: Consultancy, Speakers Bureau. Spinella: Secure Transfusion Services: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cerus Corporation: Consultancy, Research Funding. Liu: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Benjamin: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company. Corash: Cerus Corporation: Current Employment, Current equity holder in publicly-traded company.