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 a patient and produce additional normal blood cells.Forman SJ, Negrin RS, Antin JH, Appelbaum FR. Thomas' hematopoietic cell transplantation: stem cell transplantation. 5th ed. Vol. 2. New Jersey: Wiley-Blackwell; 2016. p.1416. HSCT may be autologous (the patient's own stem cells are used), syngeneic (stem cells from an identical twin), or allogeneic (stem cells from a donor).

It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma, leukemia, some types of lymphoma and immune deficiencies. In these cases, the recipient's immune system is usually suppressed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.

HSCT remains a dangerous procedure with many possible complications; it is reserved for patients with life-threatening diseases. As survival following the procedure has increased, its use has expanded beyond cancer to autoimmune diseases and hereditary skeletal dysplasias, notably malignant infantile osteopetrosis and mucopolysaccharidosis.

Medical uses

Indications Indications for stem-cell transplantation are:

Malignant (cancerous) Acute myeloid leukemia Chronic myeloid leukemia Acute lymphoblastic leukemia Juvenile myelomonocytic leukemia Hodgkin lymphoma (relapsed, refractory) Non-Hodgkin lymphoma (relapsed, refractory) Neuroblastoma Ewing sarcoma Multiple myeloma Myelodysplastic syndromes Gliomas, other solid tumors

Nonmalignant (noncancerous) Thalassemia Sickle cell anemia Aplastic anemia Fanconi anemia Malignant infantile osteopetrosis Mucopolysaccharidosis Paroxysmal nocturnal hemoglobinuria Pyruvate kinase deficiency Immune deficiency syndromes Autoimmune diseases, including multiple sclerosis

Many recipients of HSCTs are multiple myeloma or leukemia patients who would not benefit from prolonged treatment with, or are already resistant to, chemotherapy. Candidates for HSCTs include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia with defective stem cells, and also children or adults with aplastic anemia who have lost their stem cells after birth. Other conditions treated with stem cell transplants include sickle cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's sarcoma, desmoplastic small round cell tumor, chronic granulomatous disease, Hodgkin's disease and Wiskott–Aldrich syndrome. Non-myeloablative, so-called mini transplant (microtransplantation) procedures, have been developed requiring smaller doses of preparative chemotherapy and radiation therapy, allowing HSCT to be conducted in the elderly and other patients who would otherwise be considered too weak to withstand a conventional treatment regimen.

Number of procedures In 2006, 50,417 first HSCTs were recorded worldwide, according to a global survey of 1,327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. Of these, 28,901 (57%) were autologous and 21,516 (43%) were allogeneic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (55%) and leukemias (34%), and many took place in either Europe (48%) or the Americas (36%).

The Worldwide Network for Blood and Marrow Transplantation reported the millionth transplant to have been undertaken in December 2012. Erratum in: Lancet Haematol. 2015 May; 2(5): e184

In 2014, according to the World Marrow Donor Association, stem-cell products provided for unrelated transplantation worldwide had increased to 20,604 (4,149 bone-marrow donations, 12,506 peripheral blood stem-cell donations, and 3,949 cord-blood units).Charts from

Graft types

Autologous Autologous HSCT requires the extraction (apheresis) of hematopoietic stem cells (HSCs) from the patient and storage of the harvested cells in a freezer. The patient is then treated with high-dose chemotherapy with or without radiotherapy with the intention of eradicating the patient's malignant cell population at the cost of partial or complete bone marrow ablation (destruction of patient's bone marrow's ability to grow new blood cells). The patient's own stored stem cells are then transfused into their bloodstream, where they replace destroyed tissue and resume the patient's normal blood-cell production. Autologous transplants have the advantage of lower risk of infection during the immune-compromised portion of the treatment, since the recovery of immune function is rapid. Also, the incidence of patients experiencing rejection is very rare (and graft-versus-host disease impossible) due to the donor and recipient being the same individual. These advantages have established autologous HSCT as one of the standard second-line treatments for such diseases as lymphoma.

For other cancers such as acute myeloid leukemia, though, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, so the allogeneic treatment may be preferred for those conditions.

Autologous HSCT is also used as a treatment option for specific autoimmune conditions. It has been shown to be an effective treatment for multiple sclerosis in selected patients. It is used as a treatment option in cases where 'high-efficacy' treatments have failed, or in patients with aggressive, highly-active disease or other poor prognostic markers. The type of autologous HSCT used as a multiple sclerosis treatment is considered relatively safe and the serious adverse events rare. Researchers have conducted small studies using nonmyeloablative HSCT as a possible treatment for type 1 diabetes mellitus in children and adults. Results have been promising, but , speculating whether these experiments will lead to effective treatments for diabetes is premature.

Allogeneic Allogeneic HSCT involves two people – the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (human leukocyte antigen, HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the HLA gene, and a perfect match at these loci is preferred. Even if a good match exists at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely HLA-matched sibling), syngeneic (a monozygotic or identical twin of the patient – necessarily extremely rare since few patients have an identical twin, but offering a source of perfectly HLA-matched stem cells), unrelated (donor who is not related and found to have very close degree of HLA matching), or, as in the case of Haploidentical Transplantation, a half-matched relative such as a parent, child, or sibling. Unrelated donors may be found through a registry of bone-marrow donors, such as the National Marrow Donor Program (NMDP) in the U.S. A "savior sibling" may be intentionally selected by preimplantation genetic diagnosis to match a child both regarding HLA type and being free of any obvious inheritable disorder. Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic HSCTs appear to improve chances for cure or long-term remission once the immediate transplant-related complications are resolved.Venkat, Chaya (19 July 2005). "The Only Real Cure Out There, for Now " . CLL Topics, Inc.

A compatible donor is found by doing additional HLA testing from the blood of potential donors. The HLA genes fall in two categories (types I and II). In general, mismatches of the type-I genes (i.e. HLA-A, HLA-B, or HLA-C) increase the risk of graft rejection. A mismatch of an HLA type II gene (i.e. HLA-DR or HLA-DQB1) increases the risk of graft-versus-host disease. In addition, a genetic mismatch as small as a single DNA base pair is significant, so perfect matches require knowledge of the exact DNA sequence of these genes for both donor and recipient. Leading transplant centers currently perform testing for all five of these HLA genes before declaring that a donor and recipient are HLA-identical.

Race and ethnicity are known to play a major role in donor recruitment drives, as members of the same ethnic group are more likely to have matching genes, including the genes for HLA."Why race and ethnicity matter" . Be the Match. Retrieved 27 January 2014.

, at least two commercialized allogeneic cell therapies have been developed, Prochymal and Cartistem. Omidubicel was approved for medical use in the United States in April 2023.

Sources and storage of cells To limit the risks of transplanted stem-cell rejection or of severe graft-versus-host disease in allogeneic HSCT, the donor should preferably have the same HLA-typing as the recipient. About 25 to 30% of allogeneic HSCT recipients have an HLA-identical sibling. Even so-called "perfect matches" may have mismatched minor alleles that contribute to graft-versus-host disease. With recent advances in T-cell-depleting therapies such as post-transplant cyclophosphamide, haploidentical (half-matched) transplants have permitted successful transplantation of many patients who would otherwise have lacked a donor.

Bone marrow

In the case of a bone-marrow transplant, the HSCs are removed from a large bone of the donor, typically the pelvis, through a large needle that reaches the center of the bone. The technique is referred to as a bone-marrow harvest and is performed under local or general anesthesia.

Peripheral blood stem cells

Peripheral blood stem cells are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation.

Amniotic fluid Extracting stem cells from amniotic fluid is possible and may have applications for autologous and heterologous use.

Storage of HSC Unlike other organs, bone-marrow cells can be frozen (cryopreserved) for prolonged periods without damaging too many cells. This is a necessity with autologous HSCs because the cells must be harvested from the recipient months in advance of the transplant treatment. In the case of allogeneic transplants, fresh HSCs are preferred to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSCs, a preservative, dimethyl sulfoxide, must be added, and the cells must be cooled very slowly in a controlled-rate freezer to prevent osmotic cellular injury during ice-crystal formation. HSCs may be stored for years in a cryofreezer, which typically uses liquid nitrogen.

Conditioning regimens

Myeloablative