Graft-versus-tumor effect (GvT) appears after

allogeneic Allotransplant (''allo-'' meaning "other" in Greek) is the transplantation of cells, tissues, or organs to a recipient from a genetically non-identical donor of the same species. The transplant is called an allograft, allogeneic transplant, o ...

hematopoietic stem cell transplantation 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 ...

(HSCT). The graft contains donor

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

s (T lymphocytes) that can be beneficial for the recipient by eliminating residual

malignant Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...

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 Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemi ...

and lymphoid

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enla ...

, multiple myeloma and possibly

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

. It is closely linked with graft-versus-host disease (GvHD), as the underlying principle of

alloimmunity Alloimmunity (sometimes called isoimmunity) is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility ...

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 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 uni ...

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 (NK cells) as separate effectors, particularly in T-cell-depleted HLA-haploidentical HSCT. __TOC__

Graft-versus-leukemia

Graft-versus-leukemia (GvL) is a specific type of GvT effect. As the name of this effect indicates, GvL is a reaction against leukemic cells of the host. GvL requires genetic disparity because the effect is dependent on the alloimmunity principle. GvL is a part of the reaction of the graft against the host. Whereas graft-versus-host-disease (GvHD) has a negative impact on the host, GvL is beneficial for patients with hematopeietic malignancies. After HSC transplantation both GvL and GvHD develop. The interconnection of those two effects can be seen by comparison of leukemia relapse after HSC transplantation with development of GvHD. Patients who develop chronic or acute GvHD have lower chance of leukemia relapse. When transplanting T-cell depleted stem cell transplant, GvHD can be partially prevented, but in the same time the GvL effect is also reduced, because T-cells play an important role in both of those effects. The possibilities of GvL effect in the treatment of hematopoietic malignancies are limited by GvHD. The ability to induce GvL but not GvH after HSCT would be very beneficial for those patients. There are some strategies to suppress the GvHD after transplantation or to enhance GvL but none of them provide an ideal solution to this problem. For some forms of hematopoietic malignancies, for example

acute myeloid leukemia Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may inclu ...

(AML), the essential cells during HSCT are, beside the donor's T cells, the NK cells, which interact with KIR receptors. NK cells are within the first cells to repopulate host's bone marrow which means they play important role in the transplant engraftment. For their role in the GvL effect, their alloreactivity is required. Because KIR and HLA genes are inherited independently, the ideal donor can have compatible HLA genes and KIR receptors that induce the alloreaction of NK cells at the same time. This will occur with most of the non-related donor. When transplanting HSC during AML, T-cells are usually selectively depleted to prevent GvHD while NK cells help with the GvL effect which prevent leukemia relapse. When using non-depleted T-cell transplant, cyclophosphamide is used after transplantation to prevent GvHD or transplant rejection. Other strategies currently clinically used for suppressing GvHD and enhancing GvL are for example optimization of transplant condition or

donor lymphocyte infusion Donor lymphocyte (''or leukocyte'') infusion (DLI) or buffy coat infusion is a form of adoptive immunotherapy used after hematopoietic stem cell transplantation. History Formerly, the only treatment option that offered relapsed bone marrow transp ...

(DLI) after transplantation. However, none of those provide satisfactory universal results, thus other options are still being inspected. One of the possibilities is the use of cytokines. Granulocyte colony-stimulating factor (G-CSF) is used to mobilize HSC and mediate T cell tolerance during transplantation. G-CSF can help to enhance GvL effect and suppress GvHD by reducing levels of LPS and TNF-α. Using G-CSF also increases levels of Treg, which can also help with prevention of GvHD. Other cytokines can also be used to prevent or reduce GvHD without eliminating GvL, for example KGF, IL-11, IL-18 and IL-35.

References

Transplantation medicine Immunology {{oncology-stub

Graft-versus-leukemia

See also

References