Donor lymphocyte (or leukocyte) infusion (DLI) or buffy coat infusion is a form of adoptive immunotherapy used after hematopoietic stem cell transplantation.
Formerly, the only treatment option that offered relapsed bone marrow transplant patients hope of a cure was another bone marrow transplant. However, the risk of serious, life-threatening complications after a second BMT is great. One strategy of managing relapse, donor leukocyte infusion, might eliminate the need for a second BMT in some patients.[ citation needed ]
Donor lymphocyte infusion is the infusion in which lymphocytes from the original stem cell donor are infused, after the transplant, to augment an anti-tumor immune response or ensure that the donor stem cells remain engrafted. [1] [2] These donated white blood cells contain cells of the immune system that can recognize and destroy cancer cells.[ citation needed ]
The goal of this therapy is to induce a remission of the patient's cancer by a process called the graft-versus-tumor effect (GVT). The donor T-cells can attack and control the growth of residual cancer cells providing the GVT effect. It is hoped that the donor leukocyte infusion will cause GVT and lead to a remission of the patients cancer. Patients might require standard chemotherapy, to reduce the amount of cancer cells they have prior to their donor lymphocyte infusion.[ citation needed ]
Complications of DLI include acute and chronic graft-versus-host disease and bone marrow aplasia, resulting in immunosuppression and susceptibility to opportunistic infections. [3]
Aplastic anemia is a disease in which the body fails to produce blood cells in sufficient numbers. 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.
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.
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.
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.
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.
X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells.
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. These donor lymphocytes engraft, recognize recipient cells as foreign and mount an immune response against recipient tissues. 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, the recipient's immune system is not able to destroy the donor lymphocytes. This can result in transfusion associated graft-versus-host disease.
The National Marrow Donor Program (NMDP) is a nonprofit organization founded in 1986 and based in Minneapolis, Minnesota, that operates the Be The Match Registry of volunteer hematopoietic cell donors and umbilical cord blood units in the United States.
Juvenile myelomonocytic leukemia (JMML) is a serious chronic leukemia that affects children mostly aged 4 and younger. The name JMML now encompasses all diagnoses formerly referred to as juvenile chronic myeloid leukemia (JCML), chronic myelomonocytic leukemia of infancy, and infantile monosomy 7 syndrome. The average age of patients at diagnosis is 2 years old. The World Health Organization has included JMML in the category of myelodysplastic and myeloproliferative disorders.
Transplantable organs and tissues may both refer to organs and tissues that are relatively often or routinely transplanted, as well as relatively seldom transplanted organs and tissues and ones on the experimental stage.
Reticular dysgenesis (RD) is a rare, inherited autosomal recessive disease that results in immunodeficiency. Individuals with RD have mutations in both copies of the AK2 gene. Mutations in this gene lead to absence of AK2 protein. AK2 protein allows hematopoietic stem cells to differentiate and proliferate. Hematopoietic stem cells give rise to blood cells.
High-dose chemotherapy and bone marrow transplant (HDC/BMT), also high-dose chemotherapy with autologous bone marrow transplant, was an ineffective treatment regimen for metastatic breast cancer, and later high-risk breast cancer, that was considered promising during the 1980s and 1990s. With an overall idea that more is better, this process involved taking cells from the person's bone marrow to store in a lab, then to give such high doses of chemotherapy drugs that the remaining bone marrow was destroyed, and then to inject the cells taken earlier back into the body as replacement. It was ultimately determined to be no more effective than normal treatment, and to have significantly higher side effects, including treatment-related death.
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.
The haematopoietic system is the system in the body involved in the creation of the cells of blood.
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 response. 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.
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.