Hematopoietic Stem Cell Transplantation

Excerpt

Hematopoietic stem cell transplant (HPSCT), sometimes referred to as bone marrow transplant, involves administering healthy hematopoietic stem cells to patients with dysfunctional or depleted bone marrow. This procedure has several benefits. It helps to augment bone marrow function. In addition, depending on the disease being treated, it may allow for the destruction of malignant tumor cells. It can also generate functional cells that replace dysfunctional ones in cases like immune deficiency syndromes, hemoglobinopathies, and other diseases.

History and Evolution

Hematopoietic stem cell transplantation (HPSCT) was first explored for use in humans in the 1950s. It was based on observational studies in mice models, which showed that infusion of healthy bone marrow components into a myelosuppressed bone marrow could induce recovery of its function in the recipient. These animal-based studies soon found their clinical application in humans when the first successful bone marrow transplant was performed between monozygotic twins in New York in 1957 to treat acute leukemia. The performing physician, E. Donnell Thomas, continued his research on the development of bone marrow transplantation and later received the Nobel Prize for Physiology and Medicine for his work. The first successful allogeneic bone marrow transplant was reported in Minnesota in 1968 for a pediatric patient with severe combined immunodeficiency syndrome.

Since then, allogeneic and autologous stem cell transplants have increased in the United States (US) and worldwide. The Center for International Blood and Marrow Transplant Research (CIBMTR) reported over 8000 allogeneic transplants performed in the US in 2016, with an even greater number of autologous transplants; autologous transplants have steadily outpaced allogeneic transplants over time.

Definitions

Major Histocompatibility Complex (MHC)

The human MHC genes on the short arm of chromosome 6 (6p) encode for human leukocyte antigens (HLA) and are highly polymorphic. These polymorphisms lead to significant differences in the resultant expressed human cell-surface proteins. They are divided into MHC class I and MHC class II.

Human Leukocyte Antigens (HLA)

The HLA proteins are expressed on the cellular surface and play an essential role in alloimmunity. HLA class I molecules, encoded by MHC class I, can be divided into HLA-A, HLA-B, and HLA-C. These proteins are expressed on all cell types and present peptides derived from the cytoplasm and recognized by CD8+ T cells. HLA class II molecules are classified as HLA- DP, HLA-DQ, and HLA-DR, are encoded by MHC class II, can be found on antigen-presenting cells (APCs), and are recognized by CD4+ T cells.

Syngeneic Bone Marrow Transplantation

The donor and the recipient are identical twins. The advantages of this type of transplant include no risk of graft versus host disease (GVHD) or graft failure. Unfortunately, however, only a very few transplant patients will have an identical twin available for transplantation.

Autologous Bone Marrow Transplantation

The bone marrow products are collected from the patient and are reinfused after purification methods. The advantage of this type of transplant is no risk of GVHD. The disadvantage is that the reinfused bone marrow products may contain abnormal cells that can cause relapse in the case of malignancy; hence, theoretically, this method cannot be used in all cases of abnormal bone marrow diseases.

Allogeneic Transplantation

The donor is an HLA-matched family member, an unrelated HLA-matched donor, or a mismatched family donor (haploidentical).

Engraftment

The process by which infused transplanted hematopoietic stem cells produce mature progeny in the peripheral circulation.

Preparative Regimen

This regimen comprises high-dose chemotherapy or total body irradiation (TBI) or both, which are administered to the recipient before stem cell infusion to eliminate the largest number of malignant cells and induce immunosuppression in the recipient so that engraftment can occur.