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What is Hematopoietic Stem Cell Transplantation (HSCT)?

Overview

The transplantation of multipotent hematopoietic stem cells, usually taken from bone marrow, peripheral blood, or umbilical cord blood, to replicate inside a patient and produce more normal blood cells is known as hematopoietic stem-cell transplantation (HSCT). It can be autologous (using the patient’s stem cells), allogeneic (using stem cells from a donor), or syngeneic (using stem cells from a donor) (from an identical twin).

Patients with malignancies of the blood or bone marrow, such as multiple myeloma or leukemia, are the most common recipients of this procedure. Before the transplantation, the recipient’s immune system is frequently weakened using radiation or chemotherapy. Allogeneic HSCT has a high risk of infection and graft-versus-host disease.

HSCT is still a complicated surgery with a lot of risks; it’s just for people who have life-threatening illnesses. As the procedure’s success levels are rising, it’s now being used to treat autoimmune disorders and genetic skeletal dysplasias, such as malignant infantile osteopetrosis and mucopolysaccharidosis.

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Graft types

Autologous 

Autologous HSCT necessitates the extraction (apheresis) of the patient’s hematopoietic stem cells (HSCs) and freezing of the obtained cells. The patient is subsequently given high-dose chemotherapy with or without radiotherapy to remove the patient’s malignant cell population at the cost of partial or complete bone marrow ablation (the ability of the patient’s bone marrow to produce new blood cells is destroyed).

The patient’s stem cells are subsequently transfused into his bloodstream, where they replace damaged tissue and restore normal blood cell production. Because immune function recovers quickly, autologous transplants have a lower risk of infection during the immune-compromised stage of the treatment. Due to the donor and receiver being the same individual, the incidence of patients experiencing rejection is extremely rare (and graft-versus-host disease is unlikely). Because of these benefits, autologous HSCT has become a regular second-line treatment for illnesses like lymphoma.

However, in some diseases, such as acute myeloid leukemia, the lower mortality of autogenous HSCT compared to allogeneic HSCT may be balanced by a higher risk of cancer relapse and accompanying death, therefore allogeneic treatment may be preferable.

Researchers have done modest studies in children and adults to see if nonmyeloablative HSCT could be used as a therapy for type I (insulin-dependent) diabetes. Although the results have been promising, it is too early to speculate if these tests will lead to effective diabetic therapies as of 2019.

Allogeneic

The (healthy) donor and the (patient) receiver are both involved in allogeneic HSCT. Allogeneic HSC donors must match the recipient’s tissue type (human leukocyte antigen, or HLA). Variability at three or more loci of the HLA gene is used to match people, and a perfect match at these loci is preferable. Even if there is a good match at these crucial alleles, the recipient will need immunosuppressive drugs to prevent graft-versus-host disease.

Allogeneic transplant donors could be related (usually a closely HLA-matched sibling), syngeneic (a patient’s monozygotic or identical twin – extremely rare because very few patients have an identical twin, but serves as a source of perfectly HLA-matched stem cells), or unrelated (a patient’s monozygotic or identical twin, but providing a source of perfectly HLA-matched stem cells) (a donor who is not related and found to have a very close degree of HLA matching).

A registry of bone-marrow donors, such as the National Marrow Donor Program (NMDP) in the United States, can help find unrelated donors. People who want to be tested for a specific family member or acquaintance but don’t want to join any of the bone-marrow registry data banks can contact a commercial HLA testing facility and have a blood test or a mouth swab done to check whether they are a match.

A preimplantation genetic diagnosis may be used to pick a “savior sibling” who matches a child’s HLA type and is free of any clear inheritable illness. Umbilical cord blood is also used as a source of stem cells in allogeneic transplantation. Allogeneic HSCTs appear to boost the probability of cure or long-term remission by transfusing healthy stem cells into the recipient’s bloodstream to reform a healthy immune system once the acute transplant-related problems are addressed.

Additional HLA testing of potential donors’ blood is used to find a compatible donor. There are two types of HLA genes (types I and II). Mismatches in type-I genes (HLA-A, HLA-B, or HLA-C) enhance the chance of graft rejection in general. Graft-versus-host disease is more likely when an HLA type II gene (such as HLA-DR or HLA-DQB1) is mismatched. Furthermore, even a single DNA base pair mismatch is crucial, therefore precise matches necessitate knowing the exact DNA sequence of these genes for both donor and receiver. Before pronouncing a donor and recipient to be HLA-identical, leading transplant hospitals now test for all five of these HLA genes.

Members of the same ethnic group are more likely to have matching genes, including HLA genes, hence race and ethnicity are known to play a big influence in donor recruitment.

Prochymal and Cartistem are two commercialized allogeneic cell treatments that have been developed as of 2013.

References

1.   https://academic.oup.com/bfg/article/21/3/159/6545826

Author

 Yash Batra

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