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Infections After Bone Marrow Transplantation

Overview

Patients undergoing bone marrow transplantation (BMT) are at risk for granulocytopenia, impairment of barrier defenses, and impairment of cell-mediated immunity (CMI) and humoral immunity. This impairment leads to an immunocompromised state, allowing microorganisms to cause infection more easily, even those with limited pathogenicity. Patients undergoing BMT experience a sequential suppression of host defenses, allowing for various infectious processes at different phases of the transplantation process.

The term BMT is currently used to refer to the processes of bone marrow transplantation and peripheral blood stem cell transplantation.
The procedure involves the harvesting of hematopoietic stem cells from a donor (from peripheral blood or bone marrow) and then infusing these stem cells into the recipient who has had chemotherapy with or without irradiation, which generally has destroyed the cells in the recipient’s bone marrow.
Peripheral blood cells that are harvested require treatment with hematopoietic colony-stimulating factors (eg, granulocyte colony-stimulating factor [GCSF]) before infusing them into the recipient.
Because peripheral blood is much easier to access than bone marrow, this is increasingly becoming the standard method of harvesting stem cells.

BMT is currently used for patients with hematologic malignancies (eg, leukemia, lymphoma, multiple myeloma), solid tumors (eg, sarcomas, neuroblastoma, breast cancer, testicular cancer), and nonmalignant conditions (eg, aplastic anemia, autoimmune disorders, myelodysplastic syndrome, immunodeficiency syndromes, congenital disorders of metabolism).
For some of these conditions, BMT is now standard therapy; for others, it is used as a rescue when standard therapy is unsuccessful.

BMTs are classified as either autologous or allogeneic, based on the source of the hematopoietic stem cells.

In allogeneic transplantations, the stem cells are harvested from a donor who is other than the recipient of the BMT. Allogeneic transplants are used for patients with severe aplastic anemia, chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML).
Donors for these transplants may be related or unrelated; however, transplants from human leukocyte antigen (HLA)–matched sibling are associated with a lower risk of graft versus host disease (GVHD), and the recipient’s immune system tends to recover faster following transplantation.

The donor graft may be depleted of T lymphocytes, which are the main effectors of GVHD; however, with these new techniques, higher rates of graft rejection, cytomegalovirus (CMV) infection, invasive fungal infection, and Epstein-Barr virus (EBV)–associated posttransplantation lymphoproliferative disease have been noted.

Autologous transplantations involve stem cells that are harvested from the recipient patient. Syngeneic transplants refer to stem cells from an HLA-matched identical twin. Autologous transplantations are performed in patients with bone marrow that is healthy and has no disease. These types of transplantations are most frequently used to treat Hodgkin lymphoma, non-Hodgkin lymphoma, and breast cancer.
Patients with autologous transplantations tend to have more rapid recovery of their immune system than patients with allogeneic transplantations.
GVHD does not occur in patients undergoing autologous or syngeneic transplantation.

Placental or umbilical cord blood obtained immediately after birth has been used to harvest stem cells for transplantation,
primarily for use in allogeneic transplantations in children.
Whether parents should create their own stem cell donor for the purpose of treating another of their children is currently an issue of ethical debate.

Infection and GVHD remain the major source of morbidity and mortality in patients who undergo BMT.
According to the National Marrow Donor Program, of 462 patients in the United States who underwent an unrelated allogeneic BMT between December 1987 and November 1990, 66% had died by 1991, with infection as the most common primary and secondary cause of death (37% of 307 patients).
This article is focused on the common infections in patients who have undergone BMT, the risk factors for these infections, and the approaches to their prevention and treatment.

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