Transfusion-associated graft-versus-host disease

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Transfusion-associated graft-versus-host-disease
Other namesTA-GvHD
Specialty Hematology

Transfusion-associated graft-versus-host disease (TA-GvHD) is a rare complication of blood transfusion, in which the immunologically competent donor T lymphocytes mount an immune response against the recipient's lymphoid tissue. [1] These donor lymphocytes engraft, recognize recipient cells as foreign and mount an immune response against recipient tissues. [2] Donor lymphocytes are usually identified as foreign and destroyed by the recipient's immune system. However, in situations where the recipient is severely immunocompromised, or when the donor and recipient HLA type is similar (as can occur in directed donations from first-degree relatives), the recipient's immune system is not able to destroy the donor lymphocytes. This can result in transfusion associated graft-versus-host disease. This is in contrast with organ/tissue transplant associated GvHD, where matching HLA reduces the incident of the complication. [3]

Contents

Signs and symptoms

The clinical presentation is the same as GvHD occurring in other settings, such as bone marrow transplantation. TA-GvHD can develop two days to six weeks after the transfusion. [4] Typical symptoms include: [4]

Other symptoms can include cough, abdominal pain, dyspnea and vomiting. [5]

Diagnosis

Laboratory findings include pancytopenia, marrow aplasia, abnormal liver enzymes, and electrolyte imbalance (when diarrhea is present).[ citation needed ]

TA-GvHD can be suspected from a biopsy of the affected skin or liver, [4] and established by HLA analysis of the circulating lymphocytes. This testing can identify circulating lymphocytes with a different HLA type than the tissue cells of the host.[ citation needed ]

Prevention

Prevention includes gamma irradiation of the lymphocyte-containing blood components such as red blood cells, platelets and granulocytes. Irradiated blood components should be issued in the following situations: [6]

  • Intrauterine transfusions
  • Prematurity, low birthweight, or erythroblastosis fetalis in newborns
  • Congenital immunodeficiencies
  • Certain hematologic malignancies (e.g. Hodgkin lymphoma)
  • Patients undergoing hematopoietic stem cell transplantation
  • Components that are HLA matched, or directed donations from a family member
  • Patients receiving fludarabine therapy
  • Patients receiving granulocyte transfusions

Treatment

Treatment is supportive. No available form of therapy has proven effective in treating TA-GvHD and it is fatal in more than 90% of cases. [2]

Epidemiology

The incidence of TA-GvHD in immunocompromised patients receiving blood transfusions is estimated to be 0.1–1.0%, and mortality around 80–90%. Mortality is higher in TA-GvHD than in GvHD associated with bone marrow transplantation, where the engrafted lymphoid cells in the bone marrow are of donor origin (in autotransplant) and therefore the immune reaction is not directed against them.[ citation needed ]

The most common causes of death in TA-GvHD are infections and hemorrhages secondary to pancytopenia and liver dysfunction.[ citation needed ]

Related Research Articles

Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.

Aplastic anemia is a severe hematologic condition in which the body fails to make blood cells in sufficient numbers. Aplastic anemia is associated with cancer and various cancer syndromes. Blood cells are produced in the bone marrow by stem cells that reside there. Aplastic anemia causes a deficiency of all blood cell types: red blood cells, white blood cells, and platelets.

<span class="mw-page-title-main">Transplant rejection</span> Rejection of transplanted tissue by the recipients immune system

Transplant rejection occurs when transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.

Anti-thymocyte globulin (ATG) is an infusion of horse or rabbit-derived antibodies against human T cells and their precursors (thymocytes), which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia due to bone marrow insufficiency.

<span class="mw-page-title-main">Hematopoietic stem cell transplantation</span> Medical procedure to replace blood or immune stem cells

Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.

<span class="mw-page-title-main">Graft-versus-host disease</span> Medical condition

Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants.

<span class="mw-page-title-main">Apheresis</span> Medical techniques to separate one or more components of blood

Apheresis is a medical technology in which the blood of a person is passed through an apparatus that separates out one particular constituent and returns the remainder to the circulation. It is thus an extracorporeal therapy.

<span class="mw-page-title-main">Cell therapy</span> Therapy in which cellular material is injected into a patient

Cell therapy is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T-cells capable of fighting cancer cells via cell-mediated immunity in the course of immunotherapy, or grafting stem cells to regenerate diseased tissues.

Total body irradiation (TBI) is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. As the name implies, TBI involves irradiation of the entire body, though in modern practice the lungs are often partially shielded to lower the risk of radiation-induced lung injury. Total body irradiation in the setting of bone marrow transplantation serves to destroy or suppress the recipient's immune system, preventing immunologic rejection of transplanted donor bone marrow or blood stem cells. Additionally, high doses of total body irradiation can eradicate residual cancer cells in the transplant recipient, increasing the likelihood that the transplant will be successful.

<span class="mw-page-title-main">Minor histocompatibility antigen</span>

Minor histocompatibility antigen are peptides presented on the cellular surface of donated organs that are known to give an immunological response in some organ transplants. They cause problems of rejection less frequently than those of the major histocompatibility complex (MHC). Minor histocompatibility antigens (MiHAs) are diverse, short segments of proteins and are referred to as peptides. These peptides are normally around 9-12 amino acids in length and are bound to both the major histocompatibility complex (MHC) class I and class II proteins. Peptide sequences can differ among individuals and these differences arise from SNPs in the coding region of genes, gene deletions, frameshift mutations, or insertions. About a third of the characterized MiHAs come from the Y chromosome. Prior to becoming a short peptide sequence, the proteins expressed by these polymorphic or diverse genes need to be digested in the proteasome into shorter peptides. These endogenous or self peptides are then transported into the endoplasmic reticulum with a peptide transporter pump called TAP where they encounter and bind to the MHC class I molecule. This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells.

Donor lymphocyte infusion (DLI) or buffy coat infusion is a form of adoptive immunotherapy used after hematopoietic stem cell transplantation.

A humanized mouse is a mouse carrying functioning human genes, cells, tissues, and/or organs. Humanized mice are commonly used as small animal models in biological and medical research for human therapeutics.

Transplantable organs and tissues may refer to both organs and tissues that are relatively often transplanted, as well as organs and tissues which are relatively seldom transplanted. In addition to this it may also refer to possible-transplants which are still in the experimental stage.

TK is an experimental cell therapy which may be used to treat high-risk leukemia. It is currently undergoing a Phase III clinical trial to determine efficacy and clinical usefulness.

Graft-versus-tumor effect (GvT) appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells that can be beneficial for the recipient by eliminating residual malignant cells. GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune control of hematologic malignancies. This effect applies in myeloma and lymphoid leukemias, lymphoma, multiple myeloma and possibly breast cancer. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of alloimmunity is the same. CD4+CD25+ regulatory T cells (Treg) can be used to suppress GvHD without loss of beneficial GvT effect. The biology of GvT response still isn't fully understood but it is probable that the reaction with polymorphic minor histocompatibility antigens expressed either specifically on hematopoietic cells or more widely on a number of tissue cells or tumor-associated antigens is involved. This response is mediated largely by cytotoxic T lymphocytes (CTL) but it can be employed by natural killers as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT.

Microtransplantation (MST) is an advanced technology to treat malignant hematological diseases and tumors by infusing patients with granulocyte colony-stimulating factor (G-CSF) mobilized human leukocyte antigen (HLA)-mismatched allogeneic peripheral blood stem cells following a reduced-intensity chemotherapy or targeted therapy. The term "microtransplantation" comes from its mechanism of reaching donor cell microchimerism.

Guo Mei is a hematologist and associate director of 307th Hospital of Chinese People’s Liberation Army and deputy director of Radiation Research Institute.

T-cell depletion (TCD) is the process of T cell removal or reduction, which alters the immune system and its responses. Depletion can occur naturally or be induced for treatment purposes. TCD can reduce the risk of graft-versus-host disease (GVHD), which is a common issue in transplants. The idea that TCD of the allograft can eliminate GVHD was first introduced in 1958. In humans the first TCD was performed in severe combined immunodeficiency patients.

<span class="mw-page-title-main">Shimon Slavin</span> Israeli professor of medicine

Shimon Slavin, M.D., is an Israeli professor of medicine. Slavin pioneered the use of immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation for the cure of hematological malignancies and solid tumors, and using hematopoietic stem cells for induction of transplantation tolerance to bone marrow and donor allografts.

A granulocyte transfusion is a medical procedure in which granulocytes are infused into a person's blood. Granulocyte transfusions were historically used to prevent and treat infections in people with neutropenia, but the practice declined in popularity in the 1980s. Interest in the procedure increased in the 1990s due to the development of more effective methods for harvesting granulocytes and a growing population of people with severe neutropenia from chemotherapy. However, the treatment's efficacy remains poorly understood and its use is controversial.

References

  1. "Complications of Transfusion: Transfusion Medicine: Merck Manual Professional" . Retrieved 2009-02-09.
  2. 1 2 Savage WJ (June 2016). "Transfusion Reactions". Hematology/Oncology Clinics of North America. 30 (3): 619–634. doi:10.1016/j.hoc.2016.01.012. PMID   27113000.
  3. Vaillant AA, Modi P, Mohammadi O (2022). "Graft Versus Host Disease". StatPearls. Treasure Island (FL): StatPearls Publishing. PMID   30855823 . Retrieved 2023-02-02.
  4. 1 2 3 "National Healthcare Safety Network (NHSN)". www.cdc.gov. 2017-12-29. Retrieved 2018-09-18.
  5. Patel KK, Patel AK, Ranjan RR, Shah AP (September 2010). "Transfusion associated graft versus host disease following whole blood transfusion from an unrelated donor in an immunocompetent patient". Indian Journal of Hematology & Blood Transfusion. 26 (3): 92–95. doi:10.1007/s12288-010-0028-0. PMC   3002081 . PMID   21886390.
  6. Fung MK, Grossman BJ, Hillyer CD, Westhoff CM (2014). Technical manual (18th ed.). Bethesda, Md.: American Association of Blood Banks. ISBN   978-1563958885. OCLC   881812415.

Further reading