Irradiation Of Blood Products Research Articles

Transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease.

Transfusion-associated graft versus host disease.

To review the epidemiology, pathophysiology, therapeutic and preventive strategies of transfusion associated graft versus host disease (TA-GVHD) and relate the findings to the critically ill child. Review article of published medical literature related to TA-GVHD. Medline, bibliography search, published national and institutional guidelines. Original publications including prospective studies, case reports, case series, laboratory studies, and animal work. Data were extracted manually after we reviewed selected articles and assessed their contribution to knowledge of TA-GVHD. New and significant historic information from the selected publications relating to incidence, therapy, prevention, and complications of preventive therapy of TA-GVHD was incorporated. Pediatric critical care practitioners should be aware of this preventable but fatal complication of cellular blood product transfusion. High-risk categories include congenital and acquired immunodeficiency, younger age, transfusion of blood donated by family members, and transfusion with fresh whole blood. Children at risk for the development of TA-GVHD include neonates, infants, and children with congenital heart disease, not restricted to children with "classic" DiGeorge syndrome. At present, risk identification and targeted prevention are the only methods to manage TA-GVHD. Aside from minimizing cellular blood product exposure, blood product irradiation is the only established and widely available method to prevent TA-GVHD. Transfusion guidelines need to reflect a balance between the incidence of TA-GVHD and the costs of instituting irradiation to selected groups or as routine transfusion policy.

Validation of blood product irradiation doses

Dosimetry of blood irradiation using x-ray beams on a medical linear accelerator has been studied to evaluate the accuracy of a diode detector and the delivery achievable. Variations in applied doses for a standard dual field 6 MV x-ray are measured with a commercial diode detector. Results show that the diode detector measured applied in vitro doses to within 5.4% (2 standard deviations (2 SD)) of those calculated with a collapsed-cone convolution treatment-planning computer for a sample of 100 blood irradiations. Experiments involving the packing procedure of the blood products in the blood box were performed. It was found that a large proportion of the variation in the predicted and measured dose was due to the compacting of the scatter material at the base of the blood box (over a 6 month period) producing a higher density below the blood than originally scanned; hence an overall reduction of delivered dose was observed. The diode measurements (which provide an immediate printout) are recommended in conjunction with a film dosimeter such as radiochromic film, which still provides a back-up dose monitor and a visual reminder that the blood has been irradiated. It is also recommended that the blood box be completely evacuated of all scatter material every month and the base be carefully repacked to provide uniform scatter material.

Evaluation of absorbed dose-distribution in the X-ray or gamma-irradiator for blood products

Irradiation of blood products abrogates the proliferation of lymphocytes present in cellular component, which is currently the only accepted methodology to prevent transfusion-associated graft versus host disease (TA-GVHD). A range of irradiation dose levels between 15 Gy and 50 Gy is being used, but the majority of facilities are employing 15 Gy. It should, however, be recognized that the delivered dose in the instrument canister might differ from the actual dose absorbed by the blood bag. This study have evaluated the actual dose distribution under practical conditions where a container was loaded with blood products or water bags, or filled with distilled water. This approach provides data that the maximum attenuation occurred when the container was completely filled with a blood-compatible material. Thus, an error of approximately 20 percent should be considered in the dose measured in the in-air condition. A dose calibration in an in-air condition may lead to substantial underexposure of the blood products. A dose distribution study using adequately prearranged exposure period verified that the absorbed dose of 15 Gy was attained at any point in the container for both linear accelerator and gamma-irradiator. The maximal difference in the absorbed dose between measured points was 1.5- and 1.6-fold for linear accelerator and gamma-irradiator, respectively. In conclusion, using blood-compatible materials, a careful dose calibration study should be employed in which the absorbed dose of 15 Gy is obtained at the point where the lowest dose could be expected.

Blood irradiation with accelerator produced electron beams

Blood and blood products are irradiated with gamma rays to reduce the risk of graft versus hostdisease (GVHD). A simple technique using electron beams produced by a medical linearaccelerator has been studied to evaluate irradiation of blood and blood products. Variations inapplied doses for a single field 20 MeV electron beam are measured in a phantom study. Doseshave been verified with ionization chambers and commercial diode detectors. Results show that theblood product volume can be given a relatively homogeneous dose to within 6% using 20 MeVelectrons without the need to rotate the blood bags or the beam entry point. The irradiation processtakes approximately 6.5 minutes for 30 Gy applied dose to complete as opposed to 12 minutes fora dual field x-ray field irradiation at our centre. Electron beams can be used to satisfactorilyirradiate blood and blood products in a minimal amount of time.

T-cell immunodeficiency following cytotoxic antineoplastic therapy: a review.

Although cancer itself is immunosuppressive, cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency observed in cancer patients. The immunodeficiency induced by cytotoxic antineoplastic therapy is primarily related to T-cell depletion, with CD4 depletion generally more severe than CD8 depletion. Myeloablative therapy, dose-intensive alkylating agents, purine nucleoside analogs, and corticosteroids substantially increase the risk of therapy-induced immunosuppression. Restoration of T-cell populations following cytotoxic antineoplastic therapy is a complex process. Efficient recovery of CD4+ T cell populations requires thymic-dependent pathways which undergo an age-dependent decline resulting in prolonged CD4+ T-cell depletion in adults following T-cell-depleting therapy. Total CD8+ T-cell numbers recover in both children and adults relatively quickly post-therapy; however, CD8+ subset disruptions often remain for a prolonged period. The clinical management of patients with therapy-induced T-cell depletion involves the maintenance of a high index of suspicion for opportunistic pathogens, irradiation of blood products, prophylaxis for viral infections, and reimmunization in selected clinical circumstances. Future research avenues include efforts to rapidly rebuild immunity following cytotoxic antineoplastic therapy so that immune-based therapies may be utilized immediately following cytotoxic therapy to target minimal residual neoplastic disease.

T-Cell Immunodeficiency Following Cytotoxic Antineoplastic Therapy: A Review

Although cancer itself is immunosuppressive, cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency observed in cancer patients. The immunodeficiency induced by cytotoxic antineoplastic therapy is primarily related to T-cell depletion, with CD4 depletion generally more severe than CD8 depletion. Myeloablative therapy, dose-intensive alkylating agents, purine nucleoside analogs, and corticosteroids substantially increase the risk of therapy-induced immunosuppression. Restoration of T-cell populations following cytotoxic antineoplastic therapy is a complex process. Efficient recovery of CD4+ T cell populations requires thymic-dependent pathways which undergo an age-dependent decline resulting in prolonged CD4+ T-cell depletion in adults following T-cell-depleting therapy. Total CD8+ T-cell numbers recover in both children and adults relatively quickly post-therapy; however, CD8+ subset disruptions often remain for a prolonged period. The clinical management of patients with therapy-induced T-cell depletion involves the maintenance of a high index of suspicion for opportunistic pathogens, irradiation of blood products, prophylaxis for viral infections, and reimmunization in selected clinical circumstances. Future research avenues include efforts to rapidly rebuild immunity following cytotoxic antineoplastic therapy so that immune-based therapies may be utilized immediately following cytotoxic therapy to target minimal residual neoplastic disease.

Dosimetry of blood irradiation with radiochromic film.

It has been shown that radiochromic film is an ideal dosimeter for assessment and verification of delivered dose to irradiated blood products. Using a parallel opposing two-field technique on a medical linear accelerator, blood is irradiated to diminish the risk of transfusion-associated graft vs. host disease (TA-GVHD). The blood products are irradiated in a Perspex blood box to an applied dose of 29.5-31.7 Gy. Verification of applied dose has been performed with thimble ionization chambers and radiochromic film. Radiochromic film results have matched absorbed dose measurements from ionization chambers at all sites within the 'active' treatment volume within +/-6% for a 95% confidence limit. Using a sample of 100 in-vitro measurements, radiochromic film has measured the average applied dose to blood products to be 30.95+/-2.6 Gy for two standard deviations. Like currently available 'irradiated' film labels, the radiochromic film also serves as a visible reminder that the blood products have been irradiated.

Transfusion-associated graft-versus-host disease guideline on gamma irradiation of blood components

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare and usually fatal syndrome. Clinical manifestations are fever, maculopapular skin rash, nausea, vomiting, diarrhea, hepatitis and pancytopenia owing to bone marrow hypoplasia. It can occur in recipients with severe immunosuppression and in immunocompetent recipients after transfusion of cellular components from HLA homozygous donor to recipients heterozygous for that HLA haplotype. The diagnosis is made by clinical manifestation and skin biopsy. Antithymocyte globulin and high dose systemic corticosteroids are both the most used therapy. The back of knowledge about this syndrome, the rapid evolution and the absence of treatment response are related to patients bad evolution. Gamma irradiation of blood products has been the mainstay of TA-GVHD prevention. Dose of 2500 cGy is required to completely inactivate T cells. Irradiation damage red cells membrane and the red celis units can not be storage for long time after irradiation. High potassium levels is the mainly change in red cells units. White cell-reduction filters do not prevent TA-GVHD and gamma irradiation does not prevent alloimmunization or blood reactions. Only cellular components like whole blood, red cells, platelets and granulocytes need be irradiated. Ali blood components should be irradiated to: first or second-degree relatives, patients need HLA-matched platelets, recipients of allogeneic or autologous bone marrow transplantation, patients with Hodgkin's disease, patients treated with purine analogue drugs, intrauterine transfusion, pre-term infants and when congenítal immunodeficiency states is suspected. It is recommended irrradiated blood to patients with neoplastic disease when they receive intensive chemotherapy.

How to improve transfusion medicine. A treating physician's perspective.

As transfusion medicine becomes more complex, cooperative strategies are gaining increasing importance in relaying information to the treating physician and in incorporating the treating physician into the education and quality control processes. The broad domain of transfusion medicine is illustrated by the variety of disciplines involved in defining the use of products such as fresh frozen plasma and the newly released solvent-detergent-treated plasma, fibrin glue and highly purified fibrin sealant, and leukoreduced and irradiated blood products. Cooperative efforts among physicians and other personnel of multiple disciplines are essential to ensure appropriate use and continuous evaluation of blood products.

How to improve transfusion medicine. A treating physician's perspective.

Abstract As transfusion medicine becomes more complex, cooperative strategies are gaining increasing importance in relaying information to the treating physician and in incorporating the treating physician into the education and quality control processes. The broad domain of transfusion medicine is illustrated by the variety of disciplines involved in defining the use of products such as fresh frozen plasma and the newly released solvent-detergent–treated plasma, fibrin glue and highly purified fibrin sealant, and leukoreduced and irradiated blood products. Cooperative efforts among physicians and other personnel of multiple disciplines are essential to ensure appropriate use and continuous evaluation of blood products.

The desired dose distribution in blood irradiators

The irradiation of blood products is indispensable in order to avoid the otherwise associated Graft-Versus-Host-Disease. Normally a dose of 30 Gy is considered to be adequate with a minimum acceptable value of 25 Gy. Approximately 67 blood irradiators are now in operation in Germany. By means of thermoluminescence-dosimeters both dose and dose distribution in the beaker were determined in 15 institutes. Three institutes were found that they did not irradiate the blood bags with the recommended dose of 30 Gy but with 35 Gy or even 40 Gy instead. The extreme percentage dose deviations of the investigated institutes were 83.2% and 156.8% of the nominal value. The minimum percentage dose was as low as 32.1% and as high as 96.6%. On the axis of rotation of the beaker, deviations of up to 57% occurred; an average deviation of 27% being typical. Ten institutes fell short of the minimum accepted dose of 25 Gy whereas only 8 institutes achieved a mean dose in the beaker of 30 Gy or more with a maximum mean value of 38.8 Gy. Therefore regulations regarding quality assurance and dosimetry procedures for blood irradiators appear indispensable.

220 血液製剤照射装置のQCについて

220 血液製剤照射装置のQCについて

血液照射装置（γ線）による照射血液の保存に伴う血しょうＫ値の変動

血液照射装置（γ線）による照射血液の保存に伴う血しょうＫ値の変動

27-Year-Old Woman With Pancytopenia

A 27-year-old woman had a 4-week history of progressive dyspnea on exertion, palpitations, light-headedness during activity, and frontal headache. She denied having fever, cough, chest pain, or vertigo. Hematologic studies showed a hemoglobin concentration of 5.0 g/dL, a mean corpuscular volume of 102.9 fL, a total leukocyte count of 4.3 x 109/L (differential: neutrophils, 1.35 x 109; lymphocytes, 2.54 x 109; mononuclear cells, 0.39 x 109; eosinophils, 0.01 X 109; and basophils, 0.01 X 109),and a platelet count of 115 X 109/ L. She was hospitalized for further assessment. The patient's past medical history was remarkable for a chronic generalized seizure disorder; the last tonic-clonic seizure had occurred 3 months before the current admission. She experienced absence seizures daily. One episode of streptococcal pharyngitis was treated with orally administered penicillin 4 months before the current examination. Medications included valproic acid, 1 g/day in divided doses (a regimen that had been used for 7 years), and felbamate, 1,200 mg three times daily (therapy that had been initiated 7 months before hospitalization). She used nonprescription aspirin preparations for headaches. The patient had no family history of hematologic disorders, and a complete blood cell count performed 8 months previously had shown normal results. Menses were normal, and no other overt source of blood loss was identified. The patient had never received chemotherapy or radiation treatment, and no exposure to toxins was elicited. Physical examination revealed a resting tachycardia of 110 beats/min and a normal blood pressure, respiratory rate, and temperature. Pallor was noted. A grade 2 (on the basis of 1 to 6) systolic murmur was heard over the precordium. No adenopathy, splenomegaly, or neurologic deficit was detected. Two painless ecchymoses, each less than 5 em in diameter, were seen over the left deltoid muscle and anterior aspect of the thigh. On admission, an electrolyte panel, liver

Transfusion‐associated graft‐versus‐host disease in fludarabine‐treated B‐chronic lymphocytic leukaemia

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but serious complication of blood component therapy in patients with haematological malignancies. B-chronic lymphocytic leukaemia (B-CLL), however, has rarely been associated with TA-GVHD. We report three patients with advanced B-CLL who developed TA-GVHD. All these had been treated with fludarabine. Suppression of T cells by fludarabine may have contributed to an increased susceptibility to TA-GVHD. The use of irradiated blood products to prevent this complication should be considered for patients with advanced B-CLL treated with fludarabine or other purine analogues.

TRANSFUSION-INDUCED GRAFT-VERSUS-HOST DISEASE AFTER LIVER TRANSPLANTATION

Graft-versus-host disease (GVHD) occurring after liver transplantation can pose a difficult diagnostic dilemma. Similar clinical and pathologic skin and gastrointestinal manifestations can result from other causes (i.e., drugs, infections). Treatment for each of these entities differs, and the high mortality associated with GVHD makes this distinction critical. GVHD has been assumed to result from the cotransplantation of donor lymphoid tissue along with the allograft. In most instances, the patient also receives blood products during the operation, and occasionally during the postoperative period, and the lymphoid cells in these products are also a potential source of concern. In this report, we describe a patient who developed GVHD after liver transplantation. Using molecular diagnostic techniques, we determined that the source for this GVHD was not the organ donor, but was most likely nonirradiated blood products received during the hospital course. Our results suggest that transplant recipients with concomitant hematopoietic dysfunction would benefit from irradiated blood products to reduce the likelihood of this complication.

Multiple areas of intestinal atresia associated with immunodeficiency and posttransfusion graft-versus-host disease

We describe an infant with multiple segmental areas of atresia of the small and large bowel, with histologic features characteristic of the hereditary form of the disease. Posttransfusion graft-versus-host disease developed first, and then immunodeficiency was found. This report confirms the association between hereditary multiple intestinal atresia and immunodeficiency. We recommend irradiation of blood products in patients with multiple intestinal atresia pending evaluation of immune system status.

HLA homozygosity and the risk of related-donor transfusion-associated graft-versus-host disease.

Based on the prevailing interpretation of recent data implicating donor homozygosity for an HLA haplotype shared with a heterozygous recipient, it is our conclusion that the risk of TA-GVHD for a sibling of the blood donor is about half that of a parent or a child, and the risk for a grandparent, a grandchild, or a blood-related aunt, uncle, niece, or nephew is about the same as the risk for the donor's sibling. Consequently, the current recommendation and the practice of irradiating cellular blood products for transfusion to first-degree relatives but not for transfusion to more distant relatives is insufficient. We believe that the recommendation for prophylactic irradiation of cellular blood products, based on the current understanding of its apparent safety, should be extended at least to include transfusion to the donor's grandparents, grandchildren, and blood-related aunts, uncles, nieces, and nephews.

Irradiated blood products to prevent graft-versus-host disease.

Irradiated blood products to prevent graft-versus-host disease.