Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood.[1][2][3] It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic (from an identical twin).[1][2]
It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia.[2] In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.[2]
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[4][5] and hereditary skeletal dysplasias; notably malignant infantile osteopetrosis[6][7] and mucopolysaccharidosis.[8]
Contents
- 1 Medical uses
- 2 Graft types
- 3 Sources and storage of cells
- 3.1 Bone marrow
- 3.2
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood.[1][2][3] It may be autologous (the patient's own stem cells are used), allogeneic (the stem cells come from a donor) or syngeneic (from an identical twin).[1][2]
It is most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia.[2] In these cases, the recipient's immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease are major complications of allogeneic HSCT.[2]
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[4][5] and hereditary skeletal dysplasias; notably malignant infantile osteopetrosis[6]
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[4][5] and hereditary skeletal dysplasias; notably malignant infantile osteopetrosis[6][7] and mucopolysaccharidosis.[8]
Indications for stem-cell transplantation are:
Malignant (cancerous)
- Acute myeloid leukemia
- Chronic myeloid leukemia
- Acute lymphoblastic 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
- Pyruvate kinase deficiency
- Immune deficiency syndromes
- Autoimmune diseases[9]
Many recipients of HSCTs are multiple myeloma[10] or leukemia patients[11] 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[12] who have lost their stem cells after birth. Other conditions[13] 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. More recently non-myeloablative, ""mini transplant (microtransplantation)," procedures have been developed that require smaller doses of preparative chemotherapy and radiation. This has allowed 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%).[14]
The Worldwide Network for Blood and Marrow Transplantation reported the millionth transplant to have been undertaken in December 2012.[15]
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).[16]
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 his/her 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.[17]
For other cancers such as acute myeloid leukemia, though, the reduced mortality of the autogenous rel
Many recipients of HSCTs are multiple myeloma[10] or leukemia patients[11] 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[12] who have lost their stem cells after birth. Other conditions[13] 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. More recently non-myeloablative, ""mini transplant (microtransplantation)," procedures have been developed that require smaller doses of preparative chemotherapy and radiation. This has allowed 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%).[14]
The Worldwide Network for Blood and Marrow Transplantation reported the millionth transplant to have been undertaken in December 2012.[15]
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).[16]
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 patien
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%).[14]
The Worldwide Network for Blood and Marrow Transplantation reported the millionth transplant to have been undertaken in December 2012.[15]
In 2014, according to the World Marrow Donor Associat
The Worldwide Network for Blood and Marrow Transplantation reported the millionth transplant to have been undertaken in December 2012.[15]
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).[16]
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 his/her 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.[17]
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.[18]
Researchers have conducted small studies using nonmyeloablative HSCT as a possible treatment for type I (insulin dependent) diabete
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.[18]
Researchers have conducted small studies using nonmyeloablative HSCT as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising, but as of 2019[update], speculating whether these experiments will lead to effective treatments for diabetes is premature.[19][20][21]
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) or unrelated (donor who is not related and found to have very close degree of HLA matching). Unrelated donors may be found through a registry of bone-marrow donors, such as the National Marrow Donor Program in the U.S. People who would like to be tested for a specific family member or friend without joining any of the bone-marrow registry data banks may contact a private HLA testing laboratory and be tested with a blood test or mouth swab to see if they are a potential match.[22] 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.[23][24][25]
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 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.[26]
As of 2013[update], at least two commercialized allogeneic cell therapies have been developed, Prochymal and Cartistem.[27]
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.
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
[28] 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 for both autologous and heterologous uses at the time of childbirth.
Umbilical cord blood
Umbilical cord blood is obtained when a mother donates her infant's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSCs than is normally found in adult blood, but the small quantity of blood obtained from an umbilical cord (typically abo
Extracting stem cells from amniotic fluid is possible for both autologous and heterologous uses at the time of childbirth.
Umbilical cord blood
A newer treatment approach, nonmyeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone-marrow cells of the recipient.[30]A newer treatment approach, nonmyeloablative allogeneic transplantation, also termed reduced-intensity conditioning (RIC), uses doses of chemotherapy and radiation too low to eradicate all the bone-marrow cells of the recipient.[30]:320–21 Instead, nonmyeloablative transplants run lower risks of serious infections and transplant-related mortality while relying upon the graft versus tumor effect to resist the inherent increased risk of cancer relapse.[31][32] Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants.[33] This leads to a state of mixed chimerism early after transplant where both recipient and donor HSC coexist in the bone marrow space.
Decreasing doses of immunosuppressive therapy then allow donor T-cells to eradicate the remaining recipient HSCs and to induce the graft-versus-tumor effect. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate marker for the emer
Decreasing doses of immunosuppressive therapy then allow donor T-cells to eradicate the remaining recipient HSCs and to induce the graft-versus-tumor effect. This effect is often accompanied by mild graft-versus-host disease, the appearance of which is often a surrogate marker for the emergence of the desirable graft versus tumor effect, and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of immunosuppressive agents.
Because of their gentler conditioning regimens, these transplants are associated with a lower risk of transplant-related mortality, so allow patients who are considered too high-risk for conventional allogeneic HSCT to undergo potentially curative therapy for their disease. The optimal conditioning strategy for each disease and recipient has not been fully established, but RIC can be used in elderly patients unfit for myeloablative regimens, for whom a higher risk of cancer relapse may be acceptable.[30][32]
After several weeks of growth in the bone marrow, expansion of HSCs and their progeny is sufficient to normalize the blood cell counts and reinitiate the immune system. The offspring of donor-derived HSCs have been documented to populate many different organs of the recipient, including the heart, liver, and muscle, and these cells had been suggested to have the abilities of regenerating injured tissue in these organs. However, recent research has shown that such lineage infidelity does not occur as a normal phenomenon.[citation needed]
Chimerism monitoring is a method to monitor the balance between the patient's own stem cells and the new stem cells from a donor. In case the patient's own stem cells are increasing in number after treatment, this might be a sign the treatment did not work as intended. <
Chimerism monitoring is a method to monitor the balance between the patient's own stem cells and the new stem cells from a donor. In case the patient's own stem cells are increasing in number after treatment, this might be a sign the treatment did not work as intended.
HSCT is associated with a high treatment-related mortality in the recipient, which limits its use to conditions that are themselves life-threatening. (The one-year survival rate has been estimated to be roughly 60%, although this figure includes deaths from the underlying disease, as well as from the transplant procedure.)[34] Major complications include veno-occlusive disease, mucositis, infections (sepsis), graft-versus-host disease, and the development of new malignancies.
Infection
Bone-marr
Bone-marrow transplantation usually requires that the recipient's own bone marrow be destroyed (myeloablation). Prior to the administration of new cells (engraftment), patients may go for several weeks without appreciable numbers of white blood cells to help fight infection. This puts a patient at high risk of infections, sepsis, and septic shock, despite prophylactic antibiotics. However, antiviral medications, such as acyclovir and valacyclovir, are quite effective in prevention of HSCT-related outbreak of herpetic infection in seropositive patients.[35] The immunosuppressive agents employed in allogeneic transplants for the prevention or treatment of graft-versus-host disease further increase the risk of opportunistic infection. Immunosuppressive drugs are given for a minimum of 6 months after a transplantation, or much longer if required for the treatment of graft-versus-host disease. Transplant patients lose their acquired immunity, for example immunity to childhood diseases such as measles or polio. So, transplant patients must be retreated with childhood vaccines once they are off immunosuppressive medications.
Veno-occlusive disease
The injury of the mucosal lining of
The injury of the mucosal lining of the mouth and throat is a common regimen-related toxicity following ablative HSCT regimens. It is usually not life-threatening, but is very painful, and prevents eating and drinking. Mucositis is treated with pain medications plus intravenous infusions to prevent dehydration and malnutrition.
Hemorrhagic cystitis
Filgrasti
Filgrastim is typically dosed in the 10 microgram/kg level for 4–5 days during the harvesting of stem cells. The documented adverse effects of filgrastim include splenic rupture, acute respiratory distress syndrome, alveolar hemorrhage, and allergic reactions (usually experienced in first 30 minutes).[48][49][50] In addition, platelet and hemoglobin levels dip postprocedurally, not returning to normal until after a month.[50]
The question of whether geriatrics (patients over 65) react the same as patients under 65 has not been sufficiently examined. Coagulation issues and inflammation of atherosclerotic plaques are known to occur as a result of G-CSF injection. G-CSF has also been described to induce genetic changes in The question of whether geriatrics (patients over 65) react the same as patients under 65 has not been sufficiently examined. Coagulation issues and inflammation of atherosclerotic plaques are known to occur as a result of G-CSF injection. G-CSF has also been described to induce genetic changes in agranulocytes of normal donors.[49] There is no statistically significant evidence either for or against the hypothesis that myelodysplasia (MDS) or acute myeloid leukaemia (AML) can be induced by G-CSF in susceptible individuals.[51]
Blood is drawn from a peripheral vein in a majority of patients, but a central line to the jugular, subclavian, and femoral veins may be used. Adverse reactions during apheresis were experienced in 20% of women and 8% of men, these adverse events primarily consisted of numbness/tingling, multiple line attempts, and nausea.[50]
Clinical observations
Georges Mathé, a French oncologist, performed the first European bone-marrow transplant in November 1958 on five Yugoslavian nuclear workers whose own marrow had been damaged by irradiation caused by a criticality accident at the Vinča Nuclear Institute, but all of these transplants were rejected. Fortunately, the five treated were able to ultimately recover, perhaps in part due to the transplants.[52][53][54][55][56] Mathé later pioneered the use of bone marrow transplants in the treatment of leukemia.[56]
Stem-cell transplantation was pioneered using bone marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology or Medicine. Thomas' work showed that bone-marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening graft-versus-host disease.[57] Collaborating with University of Washington Professor Eloise Giblett, he discovered genetic markers that could confirm donor matches.
The first physician to perform a successful human bone-marrow transplant on a disease other than cancer was Robert A. Good at the University of Minnesota in 1968.[58] In 1975, John Kersey, M.D., also of the University of Minnesota, performed the first successful bone-marrow transplant to cure lymphoma. His patient, a 16-year-old-boy, is today the longest-living lymphoma transplant survivor.[59]
At the end of 2012, 20.2 million people had registered their willingness to be a bone-marrow donor with one of the 67 registries from 49 countries participating in Bone Marrow Donors Worldwide. Around 17.9 million of these registered donors had been ABDR typed, allowing easy matching. A further 561,000 cord blood units had been received by one of 46 cord blood banks from 30 countries participating. The highest total number of bone-marrow donors registered were those from the U.S. (8.0 million), and the highest number per capita were those from Cyprus (15.4% of the population).[60]
Within the U.S., racial minority groups are the least likely to be registered, so are the least likely to find a potentially life-saving match. In 1990, only six African Americans were able to find a bone-marrow match, and all six had common European genetic signatures.[61]
Africans are more genetic
Within the U.S., racial minority groups are the least likely to be registered, so are the least likely to find a potentially life-saving match. In 1990, only six African Americans were able to find a bone-marrow match, and all six had common European genetic signatures.[61]
Africans are more genetically diverse than people of European descent, which means that more registrations are needed to find a match. Bone marrow and cord blood banks exist in South Africa, and a new program is beginning in Nigeria.[61] Many people belonging to different races are requested to donate as a shortage of donors exists in African, mixed race, Latino, aboriginal, and many other communities.
Two registries in the U.S. recruit unrelated allogeneic donors: NMDP or Be the Match, and the Gift of Life Marrow Registry.
In 2007, a team of doctors in Berlin, Germany, including Gero Hütter, performed a stem-cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive.[62] From 60 matching donors, they selected a [CCR5]-Δ32 homozygous individual with two genetic copies of a rare variant of a cell surface receptor. This genetic trait confers resistance to HIV infection by blocking attachment of HIV to the cell. Roughly one in 1,000 people of European ancestry have this inherited mutation, but it is rarer in other populations.[63][64] The transplant was repeated a year later after a leukemia relapse. Over three years after the initial transplant, and despite discontinuing antiretroviral therapy, researchers cannot detect HIV in the transplant recipient's blood or in various biopsies of his tissues.[65] Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV, but scientists emphasise that this is an unusual case.[66] Potentially fatal transplant complications (the "Berlin patient" suffered from graft-versus-host disease and leukoencephalopathy) mean that the procedure could not be performed in others with HIV, even if sufficient numbers of suitable donors were found.[67][68]
In 2012, Daniel Kuritzkes reported results of two stem-cell transplants in patients with HIV. They did not, however, use donors with the Δ32 deletion. After their transplant procedures, both were put on antiretroviral therapies, during which neither showed traces of HIV in their blood plasma and purified CD4+ T cells using a sensitive culture method (less than 3 copies/ml). The virus was once again detected in both patients some time after the discontinuation of therapy.[69]In 2012, Daniel Kuritzkes reported results of two stem-cell transplants in patients with HIV. They did not, however, use donors with the Δ32 deletion. After their transplant procedures, both were put on antiretroviral therapies, during which neither showed traces of HIV in their blood plasma and purified CD4+ T cells using a sensitive culture method (less than 3 copies/ml). The virus was once again detected in both patients some time after the discontinuation of therapy.[69]
In 2019, a British man became the second to be cleared of HIV after receiving a bone-marrow transplant from a virus-resistant (Δ32) donor. This patient is being called "the London patient" (a reference to the famous Berlin patient).[70]
Since McAllister's 1997 report on a patient with multiple sclerosis (MS) who received a bone-marrow transplant for CML,[71] over 600 reports have been published describing HSCTs performed primarily for MS.[72] These have been shown to "reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients" who have aggressive, highly active MS, "in the absence of chronic treatment with disease-modifying agents".[72] A randomized clinical trial including 110 patients showed that HSCT significantly prolonged time to disease progression compared to disease-modifying therapy.[73] Long-term outcome in patients with severe disease has showed that complete disease remission after HSCT is possible.[74]
Other autoimmune neurological diseases
