Transfusion-associated Graft-versus-host Disease Research Articles

Perspectives on Transfusion-Associated Graft-Versus-Host Disease

Perspectives on Transfusion-Associated Graft-Versus-Host Disease

喉摘術後輸血により発生したGVHDの1例

We present a rare case of post-trasfusion Graft Versus Host Disease (GVHD) that developed in a patient treated for laryngeal cancer. A 65-year-old man with laryngeal cancer (T2N1M0) underwent total laryngectomy with right radical neck dissection after 30 Gy irradiation and chemotherapy with CBDCA and 5-FU. Blood loss volume during surgery was 890 ml and he was transfused with 3 U of packed red blood cells. On the fifth day after blood transfusion, high fever (39.0°C) developed. On the 7th day, erythema appeared over the whole body. Thereafter, liver dysfunction and pancytopenia developed. The patient died of heart failure on the 34th day. Prevention of transfusion-associated GVHD is very important because the mortality rate is more than 90%. Therefore, should be treated products with gamma radiation before transfusion or autologous blood should be used as a safety precaution.

Potential for transfusion-associated graft-versus-host disease due to apheresis platelets matched for HLA class I antigens.

Transfusion-associated graft-versus-host disease (TA-GVHD) has been reported in immunocompetent recipients of nonirradiated cellular blood components from donors who are homozygous for an HLA haplotype shared with the patient. In these cases, donor lymphocytes have no antigens foreign to the recipient, and this similarity in HLA antigens appears important for the development of TA-GVHD. Experience with 65 patients receiving apheresis platelets matched for class I HLA antigens was reviewed to determine the incidence of such a transfusion among HLA-matched, unrelated donor-recipient pairs. In 5 percent of transfusions (31/673), the patient received lymphocytes from a donor exhibiting no antigens foreign to the recipient, but the patient had additional HLA-A or -B antigens not present on donor lymphocytes. Twenty-three percent (n = 15) of patients received at least one such transfusion. In addition, most patients were immunosuppressed as a result of their underlying disease or therapy, which may decrease the degree of antigen matching required to initiate TA-GVHD. Until the pathogenesis of this disease is better understood, it is recommended that the transfusion of an HLA-matched cellular blood component be considered a risk factor for the development of TA-GVHD regardless of the patient's immune status, and that all such blood components be irradiated.

Transfusion‐associated graft‐versus‐host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second‐degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion-associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one-way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA-GVHD.

The effects of gamma irradiation versus white cell reduction on the mixed lymphocyte reaction

The risk of transfusion-associated graft-versus-host disease (TA-GVHD) is related to the number of viable T cells transfused. Whether white cell (WBC)-reduced blood components would carry a decreased risk of TA-GVHD was considered, and the allogeneic mixed lymphocyte reaction was used as an in vitro model for TA-GVHD. An exponential decline in the mixed lymphocyte reaction was found to occur, as a result of either an arithmetic increase in the dose of gamma irradiation given to responding cells or a logarithmic decrease in the number of unirradiated responding cells. Irradiation of responding cells with 600 cGy or a 0.6 log10 reduction in the number of responding cells produced a 95-percent decline in the mixed lymphocyte reaction. Although these studies do not validate the use of WBC reduction as a substitute for gamma irradiation for the prevention of TA-GVHD, they suggest that the relative risk of TA-GVHD resulting from the use of standard cellular components versus WBC-reduced components merits further investigation.

Graft-versus-Host Disease Associated with Transfusion of Blood from Unrelated HLA-Homozygous Donors

Graft-versus-host disease (GVHD) is a well-known complication of allogeneic bone marrow transplantation and is increasingly being recognized after solid-organ transplantation and transfusion1–3. Like GVHD occurring after bone marrow transplantation, transfusion-associated GVHD is characterized by fever, skin rash, diarrhea, and hepatitis. However, transfusion-associated GVHD typically occurs much sooner (median, 10 to 12 days after transfusion), is frequently associated with bone marrow aplasia, usually does not respond to immunosuppressive therapy, and is fatal in most cases4–10. Since gamma irradiation of cellular blood components before transfusion can prevent the development of transfusion-associated GVHD, it is critical to identify susceptible . . .

Transfusion-Associated Graft Versus Host Disease Following Hepatectomy for Hepatocellular Carcinoma. A Case Report.

A case of transfusion-associated graft versus host disease (TA-GVHD) following hepatectomy for hepatocellular carcinoma is described in a 53 year-old male patient. The intraoperative bleeding was estimated to be 1220 ml, and he was transfused with 4 units of fresh whole blood. On postoperative day (POD) 12, a fever of 38 degrees C developed, followed by a systemic erythema on POD 14, and a marked progressive leukopenia starting from POD 19. The patient died of multiple organ failure (MOF) on POD 29. Just before death, the results of skin, bone marrow, and liver biopsies had no physical evidence of GVHD. TA-GVHD was found in the HLA typing of the patient's family. This TA-GVHD case was considered to be a reduced immunity due to severe surgical stress or preoperative transcatheter arterial embolization (TAE), in view of the fact that he was transfused with fresh whole blood during the operation. TA-GVHD has frequently been reported in patients after open heart surgery, but also after hepatectomy. It is therefore necessary to take all available means to prevent it by restricting the use of blood preparations as much as possible, and if hetero blood transfusions are performed, blood should be irradiated prior to transfusion.

The effect of prestorage irradiation on posttransfusion red cell survival.

Transfusion-associated graft-versus-host disease (TA-GVHD) may occur whenever immunologically competent allogeneic lymphocytes are transfused to an immunocompromised recipient. Irradiation of blood components eliminates the risk of TA-GVHD but may damage the cellular elements in the transfused component, particularly if the cells are stored for prolonged periods in the irradiated state. To study the effect of irradiation on long-term storage of red cells, AS-1 red cells from eight normal subjects were prepared on two occasions. On one occasion, the units were stored as standard AS-1 red cells for 42 days at 4 degrees C; on the other, they were exposed to 3000 cGy radiation within 4 hours of collection and then were stored as AS-1 red cells for 42 days at 4 degrees C. The donations were at least 12 weeks apart. Irradiated units demonstrated significant elevations in poststorage plasma hemoglobin (Hb) (623 +/- 206 vs. 429 +/- 194 g/dL [6230 +/- 2060 vs. 4290 +/- 1940 g/L], p less than 0.02) and plasma potassium (78 +/- 4 vs. 43 +/- 9 mEq/L [78 +/- 4 vs. 43 +/- 9 mmol/L], p less than 0.01) and significant decreases in red cell ATP (1.9 +/- 0.2 vs. 2.1 +/- 0.3 microM/g Hb, p less than 0.04) and 24-hour posttransfusion red cell recovery (68.5 vs. 78.4%, p less than 0.02), as compared to nonirradiated units. It can be concluded that irradiation with 3000 cGy damages red cells and that long-term storage in the irradiated state may enhance this damage. Red cells should not be stored for 42 days after irradiation with 3000 cGy.

Ultraviolet irradiation modulates MHC-alloreactive cytotoxic T-cell precursors involved in the onset of graft-versus-host disease.

Ultraviolet B (UVB) irradiation of cellular blood components has been proposed as a new technology to prevent HLA sensitization in recipients. Earlier studies have shown that a dose of 2 J/cm2 abrogates the ability of lymphocytes to serve as stimulators in mixed lymphocyte cultures (MLC). In this study we have evaluated the effect of UV energy on T-lymphocytes for the prevention of transfusion-associated graft-versus-host disease (TA-GvHD). The response of cytotoxic T-lymphocyte precursors against host alloantigens was almost undetectable at a dose of 0.5 J/cm2. T-cell proliferation in MLC or in response to phytohaemagglutinin was inhibited by more than 95% at doses of 1 J/cm2 or higher. The data suggest that UV irradiation can be used to prevent both HLA sensitization and TA-GvHD in recipients.

Transfusion‐associated graft‐versus‐host disease in a presumably immunocompetent patient after transfusion of stored packed red cells

A 54-year-old woman developed transfusion-associated graft-versus-host disease (TA-GVHD) after the transfusion of stored packed red cells obtained from unrelated donors. The patient was presumed to be immunocompetent. A diagnosis of TA-GVHD was made by clinical features and postmortem pathologic findings. Sex chromatin analysis of the patient's lymphocytes demonstrated chimerism. HLA typing of the blood donors revealed one to be HLA-homozygous for one of the patient's HLA haplotypes (A33-B44-Cblank). This case illustrates the risk in the general patient population of TA-GVHD after routine blood transfusion therapy. Workers should be aware of this possibility and should continue searching for an efficient way to prevent it.

Transfusion‐associated graft‐versus‐host disease: do transfusions from second‐degree relatives pose a greater risk than those from first‐ degree relatives?

When a patient receives blood from a closely related donor, there is the potential for transfusion-associated graft-versus-host disease (TA-GVHD). With a mathematical model, the potential risk of TA-GVHD was derived for six classes of related donors. This risk was considered to be present when an HLA-heterozygous patient received blood from a donor who was homozygous for one of the patient's haplotypes. Calculations showed that second-degree related donors present a greater risk of TA-GVHD than some (siblings) but not all (parents, children) first-degree related donors. Moreover, there is, in general, no sharp cutoff of risk among the various classes of donors. These results should be considered in the determination of a policy for the irradiation of directed-donor units.

血縁者間の輸血によって輸血後移植片対宿主病を起こすリスクについて

Transfusion-associated graft-versus-host disease (TA-GVHD) was described as occurring after nonirradiated blood tranfusion not only in immunosuppressed but also in immunocompetent recipients who share one HLA haplotype with HLA-homozygous blood donors.From the distribution of 1% or more frequencies of HLA-A, -B, -C, -DR, -DQ haplotypes obtained at the 11th International Histocompatibility Workshop (1991), using the fomulae of Kanter, we tried to calculate the potential risk of TA-GVHD as a result of directed donations from relatives in the Japanese and other ethnic groups.The Japanese have the greatest risk of TA-GVHD than any other populations because are more homogeneous in HLA and have a common haplotype: A24-CBL-Bw52-DRw15-DQw1 (7.5%).Of noteworthing, the risk of transfusion of HLA-homozygotes to heterozygotes among 1st-degree relatives in the Japanese was 4.7-folds compared with that of transfusion in the U. S. A. population. And, the risk of TA-GVHD among the Japanese unrelated was near to that of transufusion among the French first degree relatives.Therefore, we recommend that donations of blood components from recipient's relatives should be irradiated essentially, and as possible even from unrelated donors in the Japanese population.

Transfusion-associated graft-versus-host disease: historical perspectives, incidence, and current use of irradiated blood products.

Transfusion-associated graft-versus-host disease (TGVHD) has been reported in 131 patients as a complication of supportive treatment with an overall 90% mortality. This study was undertaken to define the historical incidence of TGVHD, its symptomatology, and mortality among affected patients by age, diagnosis, and blood product transfused. Although the use of irradiated blood products (IBPs) virtually eliminates the risk of this highly lethal complication, the use of IBPs appears variable. To ascertain current use of IBPs, questionnaires were sent to 100 pediatric and adult hematologists, oncologists, and bone marrow transplant physicians asking their perceptions about and actual use of IBPs. The results of the questionnaire, information on irradiation effects on cellular blood products, and current recommendations for irradiation of blood products are discussed.

Variation in blood component irradiation practice: implications for prevention of transfusion-associated graft-versus-host disease

RAFT-VERSUS-HOST DISEASE (GVHD) is comG monly observed after allogeneic bone marrow transplantation (BMT), but transfusion-associated (TA) GVHD is only rarely reported. Although early reports of TAGVHD were recognized in immunocompromised hosts, more recent cases have been documented in immunocompetent transfusion recipients. The increasing awareness of this serious complication of transfusion prompted a national survey of transfusion medicine practices to identify patients at risk for TA-GVHD and assess methods for its prevention. HISTORICAL PERSPECTIVE The reported cases of TA-GVHD have recently been summarized.' To date, it has been documented after transfusion of unirradiated blood components to at least 87 patients: in patients with severe combined immunodeficiency, thymic hypoplasia, and Wiskott Aldrich syndrome2.'*; premature newborns and those with erythroblastosis fetali~'~-*~; patients with hematologic malignancies including Hodgkin's and non-Hodgkin's lymphomas, acute myelocytic and lymphoblastic leukemias, chronic lymphocytic leukemia, and aplastic patients with solid tumors including neuroblastomas, glioblastoma, rhabdomyosarcoma, cervical carcinoma, small cell lung cancer, and germ cell tum08'-'~; patients after cardiac surgery and cholecystectomp-60; and in an apparently healthy 22-year-old woman.6' This syndrome has developed after neonatal exchange and intrauterine transfusions; and after transfusion of whole blood, fresh (nonfrozen) plasma, red blood cells, and platelets. Leukocytes harvested from normal donors and from donors with chronic myelocytic leukemia transfused to patients with hematologic malignancies have also been implicated in TA-GVHD. TA-GVHD results in an overall mortality of 84% at a median of 21 (8 to 1,050) days after transfusion.'

Transfusion associated graft‐versus‐host disease after cardiac surgery: response to antithymocyte‐globulin and corticosteroid therapy

A 63-year-old patient developed graft-versus-host disease (GVHD) after the transfusion of stored, random donor red cell concentrates with coronary artery surgery. The disease was characterised by skin rash, fever, diarrhoea, hepatic dysfunction, pancytopenia and the acquisition of cells bearing human leukocyte antigens of a blood donor. Clinical and histologic improvements were noted with antithymocyte-globulin and corticosteroid therapy, as seen in some patients with acute GVHD following allogeneic bone marrow transplantation, but the pancytopenia failed to resolve prior to a fatal cerebral haemorrhage. Early aggressive immunosuppressive therapy may be beneficial for transfusion-associated GVHD but strategies for its prevention by limitation of the use of homologous blood need to be addressed.

Fatal erythroderma (suspected graft‐versus‐host disease) after cholecystectomy. Retrospective analysis

Fatal postoperative erythroderma (POE) developed in a 52-year-old woman with gallstones who underwent elective cholecystectomy. During surgery, she was transfused with 3 units of unirradiated packed red cells stored in the liquid state for at least 4 days after collection. The POE is believed to have been the result of transfusion-associated graft-versus-host disease (TA-GVHD). The diagnosis of GVHD was based upon the characteristic clinical picture and retrospective HLA typing. The implicated donor was homozygous for an HLA haplotype that appeared to be shared with the recipient: A24-CBL-Bw52-DR2-DRw52-DQw1, the most common haplotype in the Japanese population. This case raises the possibility that a transfusion of relatively fresh blood from a donor who has no HLA antigens incompatible with the recipient may result in GVHD in patients with no apparent immunoincompetence who are undergoing relatively minor surgery with no chemotherapy or radiation therapy.