The Role of Blood from HLA-Homozygous Donors in Fatal Transfusion-Associated Graft-versus-Host Disease after Open-Heart Surgery

Thaler, Michael; Shamiss, Ari; Orgad, Shlomit; Huszar, Monica; Nussinovitch, Naomi; Meisel, Simcha; Gazit, Ephraim; Lavee, Jacob; Smolinsky, Aram

doi:10.1056/nejm198907063210105

Cited by 221 publications

(75 citation statements)

References 11 publications

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“…21 In addition, transfusional GVHD in immunodeficient infants is characterized by the development of severe GVHD and aplastic anemia, as is transfusional GVHD in immunocompetent patients after open heart surgery. 22,23 In all the above examples, donor T-lymphocytes mediate host hematopoietic stem cell destruction and lead to the development of marrow aplasia and severe pancytopenia. However, unlike our experience, fatal GVHD developed in all the reported recipients.…”

Section: Resultsmentioning

confidence: 99%

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency

Rubocki

Parsa

Hershfield

et al. 2001

Blood

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IntroductionSevere combined immunodeficiency (SCID) involves a failure of T cells to proliferate to various stimuli and a failure of B cells to produce specific antibodies. 1,2 Adenosine deaminase (ADA) deficiency, an autosomal recessive genetic defect, produces a SCID phenotype. 3,4 The enzyme defect leads to an abnormality in purine nucleoside metabolism that interferes with lymphocyte viability and function. ADA-deficient SCID is characterized by growth delay, candidiasis, respiratory infections, opportunistic infections, and, without specific therapy, early death. 5 Low or absent ADA activity in erythrocytes or other cells is diagnostic.Bone marrow transplantation (BMT) is effective therapy for SCID. The profound T-cell dysfunction associated with ADAdeficient SCID prevents graft rejection and permits BMT without conditioning with an HLA-matched sibling donor. 1,2,6 Success rates are greater than 90%, with full recovery of T-cell and B-cell functions. 6 Complete T-cell engraftment is routinely demonstrated, and approximately 50% of patients demonstrate engraftment of donor B cells. 7 Without conditioning, host hematopoiesis persists with no evidence of myeloid or erythroid engraftment. 5,[7][8][9] Study design J.L., a 17-month-old girl, presented with fever, vomiting, cough, skin ulcers, a history of failure to thrive, recalcitrant thrush, chronic respiratory infections, and recurrent otitis media. Immunizations were current. Family history was negative for immunodeficiency. Physical examination revealed an ill-appearing white female with weight and height below the fifth percentile, a paucity of lymph nodes, and no hepatosplenomegaly.Laboratory evaluation revealed normal hemoglobin and platelet counts. The white blood cell count was 1600/cmm (normal, 6000-17 000/cmm) and consisted of 10% neutrophils, 20% lymphocytes, 65% monocytes, and 4% eosinophils. Liver function test results were normal. Titers were negative for human immunodeficiency virus, cytomegalovirus, hepatitis B virus, herpes simplex virus, Epstein-Barr virus, adenovirus, poliovirus, Toxoplasma, and Chlamydia trachomatis.ADA activity was deficient in erythrocytes and in peripheral blood mononuclear cells; purine nucleoside phosphorylase (PNP) activity was normal in both cell types (Table 1). Metabolic findings in erythrocytes were consistent with ADA deficiency, including elevated deoxyadenosine nucleotide (dAXP) of 0.491 mol/mL packed cells (normal, less than 0.002 M/mL), and reduced S-adenosylhomocysteine hydrolase activity of 0.42 nmol/h/mg protein (normal, 4.2 Ϯ 1.9). 3 A 3-year-old sister was HLA-identical (A2, A3, B35, B27, Cw2, Cw4, DRB1*01, and DRB1*04). Without myeloablative or immunosuppressive therapy, the patient was infused with 7.6 ϫ 10 8 unfractionated nucleated marrow cells per kilogram from her sister. After BMT, the patient engrafted rapidly, remained well, and required no blood products (Figure 1). Biopsy-proven grade I skin graft-versus-host disease (GVHD) developed at day 39 after BMT and resolved with topical corticosteroid...

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Section: Resultsmentioning

confidence: 99%

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency

Rubocki

Parsa

Hershfield

et al. 2001

Blood

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“…7 In 1989, a group of Israeli cardiac surgeons observed postoperative erythroderma in 2 immunocompetent patients who received HLA homozygous whole-blood transfusions, but because the histology of the skin lesions was very similar to previously described GVHD histology, they stated that postoperative erythroderma is a skin manifestation of GVHD and that GVHD could also occur in immunocompetent patients who received transfusions of nonirradiated blood products from HLA-homozygous donors for 1 of the recipient's haplotypes. 8 PATHOGENESIS OF TA-GVHD Transfused T lymphocytes are the cause of TA-GVHD, wherein it is believed that both CD4 þ and CD8 þ T lymphocytes play critical roles. Current models indicate that the initial activation of helper CD4 þ cells by foreign HLA antigens is followed by the activation of cytotoxic CD8 þ cells, which then mediate much of the pathology of this disorder.…”

Section: History Of Gvhdmentioning

confidence: 99%

“…In contrast, if the recipient is immunocompromised and/or the transfused T lymphocytes are HLA homozygous for 1 of the recipient's haplotypes (even in an immunocompetent recipient), then the recipient's immune system will consider these cells as self so that these T lymphocytes can engraft, proliferate, and attack the host (Figure). 8,[11][12][13][14] The minimum number of lymphocytes required for engraftment is 1 3 10 7 cells per kilogram, and various blood products contain different amounts of lymphocytes (Table 1). 9,15 The risk of TA-GVHD depends on the degree of HLA homogeneity between donor and recipient; high degrees of homogeneity are found in certain countries, such as Japan and Israel, or in blood relatives in more diverse populations.…”

Section: History Of Gvhdmentioning

confidence: 99%

Prevention of Transfusion-Associated Graft-Versus-Host Disease With Blood Product Irradiation: The Past, Present, and Future

Bahar¹,

Tormey

2018

Archives of Pathology &Amp; Laboratory Medicine

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Transfusion-associated graft-versus-host disease (TA-GVHD) is a disease with a very high mortality rate. In this report, we discuss TA-GVHD from a historical perspective, highlight the pathogenesis of TA-GVHD, and emphasize the importance of blood product irradiation, which is a very effective means to prevent this disease. We summarize the current recommendations in different patient populations from different countries and review recent developments, such as alternatives for the use of radioactive materials. We also speculate on future directions.

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“…Subsequently, recognition of the development of TA-GVHD as a result of human leukocyte antigen (HLA) similarities between the donor and recipient added to the understanding of the development of the condition. 4 In 2015, a systematic review of reported cases of TA-GVHD was published. This review supported the notion that TA-GVHD occurs primarily as a consequence of transfusion of viable donor lymphocytes; however, rather than occurring primarily in immunocompromised patients, this work favored HLA haplotype homozygosity as the dominant mechanism for development of TA-GVHD.…”

mentioning

confidence: 99%

Survey of Irradiation Practice for the Prevention of Transfusion-Associated Graft-versus-Host Disease

Pritchard

Shaz²

2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.—Transfusion-associated graft-versus-host disease is a rare, often fatal complication of cellular blood product transfusion. The requirement that at-risk groups receive irradiated products reduces the incidence of transfusion-associated graft-versus-host disease. A comprehensive survey of irradiation practices has not been performed since 1989; meanwhile, new indications for irradiation have emerged. Objective.—To assess current irradiation practices at College of American Pathologists member institutions. Changes in irradiation practice indicated by comparing results of a survey of irradiation practices in 1989 with those of a survey performed in 2014 may reveal how the field has developed and what areas (if any) remain to be improved. Design.—A supplemental College of American Pathologists survey was sent out with questions regarding irradiation practices for specific conditions and circumstances. The questions included conditions for which irradiation is generally considered required for the prevention of transfusion-associated graft-versus-host disease as well as those not considered to be a special risk. Results.—An average of 2100 organizations responded to each question regarding their irradiation practices. Irradiation for transfusion from blood relatives, human leukocyte antigen–matched products, preterm infants, and Hodgkin disease were the most common indications cited. A few organizations had universal irradiation, whereas others irradiated products by floor/unit or by service. Conclusions.—For some at-risk populations irradiation of cellular blood products is more common than in 1989, whereas for others this practice has been reduced. Although gains have been made since the last national survey of irradiation practices, work remains to eliminate the possibility of transfusion-associated graft-versus-host disease from known at-risk populations.

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The Role of Blood from HLA-Homozygous Donors in Fatal Transfusion-Associated Graft-versus-Host Disease after Open-Heart Surgery

Cited by 221 publications

References 11 publications

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency

Full hematopoietic engraftment after allogeneic bone marrow transplantation without cytoreduction in a child with severe combined immunodeficiency

Prevention of Transfusion-Associated Graft-Versus-Host Disease With Blood Product Irradiation: The Past, Present, and Future

Survey of Irradiation Practice for the Prevention of Transfusion-Associated Graft-versus-Host Disease

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