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Category Archives: Stem Cell Transplant
Posted: November 1, 2015 at 5:44 pm
Vanderbilt-Ingram Cancer Center performs around 215 stem cell and bone marrow transplants each year, providing care leading up to the transplant, through all aspects of the procedure, and indefinitely after the transplant to monitor for complications. To address some common questions about the procedure, we spoke with Madan Jagasia, M.D., director of the Outpatient Transplant Program and section chief for Hematology and Stem Cell Transplant at Vanderbilt-Ingram.
What is a stem cell? (click to enlarge)
Stem cells or more specifically, in this case, hematopoietic stem cells are cells that can give rise to all the different types of mature blood cells the red blood cells that carry oxygen, the platelets involved in blood clotting, and a host of white blood cells, which are part of the bodys immune system and provide defense against infectious agents. Stem cells are self-renewing (i.e., they can produce more of themselves) and reside primarily in the bone marrow but also circulate in the blood.
For a stem cell transplant, the stem cells can come from a related or unrelated donor, from umbilical cord blood, or from the patient him/herself.
No, these are adult stem cells, from the blood or bone marrow. Even when the source of stem cells is umbilical cord blood, these are still adult stem cells and have nothing to do with embryonic stem cells.
Most of the stem cell transplants we do in adult patients are for bone marrow, blood or lymph node cancers. For example, in acute leukemia, the DNA of immature white blood cells is somehow damaged, which causes one or more of the white blood cell types to grow rapidly and accumulate in the blood. These abnormal cells do not function properly and crowd out normally functioning blood cells.
With a stem cell transplant (SCT), the patients stem cells are replaced with stem cells from either a healthy donor (called an allogeneic transplant) or with the patients own stem cells (called an autologous transplant). The goal is for the new stem cells to begin producing a new, properly functioning set of circulating blood cells.
Transplants can also be used to treat other blood and bone marrow diseases, like sickle cell anemia or thalassemia, for example.
An autologous transplant is more like a stem cell rescue than a true transplant it is just removing the stem cells and giving them back to the patient. We do bone marrow biopsies as part of the transplant process to make sure that the marrow is not heavily contaminated (with malignant cells). And from previous research, we know that if/when the cancer comes back, it is because of residual cancer cells in the patient that were not killed by the chemotherapy, not from the stem cells that were infused back.
Stem cell transplant illustration (click to enlarge)
In an autologous transplant, we collect the patients stem cells, treat the patient with high-dose chemotherapy and/or radiation to hopefully kill the cancer and destroy the existing bone marrow, and then infuse the stem cells back intravenously, which become the new marrow.
In donor (allogeneic) transplants, we dont always need as high a dose of chemotherapy for adult patients. The goal of the chemotherapy (in some patients, radiation is used along with chemotherapy) is to kill the recipients immune system, so that the donor cells wont be rejected. The donor immune system then fights the tumor a phenomenon that is called graft-versus-tumor effect.
The infused stem cells find their way to the bone marrow, where they will start producing blood cells. This generally takes around two weeks, but can take longer (three to four weeks) for stem cells from umbilical cord. By monitoring blood cell counts, we know when this engraftment of the stem cells has occurred.
In time, the donor cells which we call the graft begin attacking the patients remaining tumor cells. We call this graft-versus-tumor effect, and thats what leads to remission or cure.
Possibly. The challenge in allogeneic transplants is something called graft-versus-host disease (GVHD). The graft doesnt really know the difference between a patients tumor cells and healthy cells, so the donor cells may attack healthy tissue. GVHD is the bottleneck of transplantation today, so we try to limit or treat the damage done by the donors immune cells with steroids and other therapies. (See When the Treatment Fights Back)
The success rate or cure rate the percentage of patients living five years or more beyond transplant just depends on the disease for which the transplant was done and the source of the cells transplanted. To give examples of the extremes: for a person in their 20s with aplastic anemia (a bone marrow failure syndrome) receiving a related donor transplant, the cure rate is about 90 percent; on the other extreme, for someone with advanced relapsed leukemia receiving stem cells from umbilical cord blood, the cure rate might be between 10 percent and 15 percent.
Categories Summer 2012
Tags allogeneic transplant autologous bone marrow hematology Madan Jagasia Outpatient Transplant Unit stem cell transplant stem cells Summer 2012
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Understanding Stem Cell Transplant VICC Momentum
Posted: October 31, 2015 at 1:43 pm
What is a stem cell transplant?
A stem cell transplant may be used so that you can have intensive high-dose chemotherapy (and sometimes radiotherapy) to kill cancerous cells. The chemotherapy is higher than conventional chemotherapy and also kills the stem cells in the bone marrow that would normally make blood cells. Therefore, following the chemotherapy, you are given back (transplanted) stem cells which can then make normal blood cells again.
A stem cell transplant is sometimes called a bone marrow transplant. However, stem cells can be obtained from blood as well as from the bone marrow. So, the term stem cell transplant is now used.
I’ve been concerned about lymphoma for two years.
Blood cells are made in the bone marrow, by stem cells. Bone marrow is the soft sponge-like material in the centre of bones. Large flat bones such as the breastbone (sternum) and pelvis contain the most bone marrow. To make blood cells constantly you need a healthy bone marrow. You also need nutrients from your diet, including iron and some vitamins.
Stem cells are immature (primitive) cells. There are two main types in the bone marrow – myeloid and lymphoid stem cells. These derive from even more primitive cells called common pluripotent stem cells. Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages (precursor or blast cells) before forming into fully formed (mature) blood cells.
Mature blood cells are released from the bone marrow into the bloodstream. Mature blood cells are:
Stem cells rapidly multiply to make millions of blood cells each day. Because of this they are more easily killed by chemotherapy than most other cells in the body. This is because chemotherapy medicines work by killing rapidly dividing cells (such as cancer cells).
A stem cell transplant is an option which is considered for various cancer conditions. For example, for types of leukaemia, lymphoma and myeloma. Your specialist will advise when it may be an appropriate option. As a rule, it is not often a first-line treatment. Conventional chemotherapy or other treatments tend to be used first. However, the treatment of cancer and leukaemia is a changing and developing area of medicine. Techniques such as stem cell transplant continue to be refined and improved and may be considered in various different circumstances.
The higher doses of chemotherapy and radiotherapy that can be used in conjunction with a stem cell transplant can improve the chance of a cure for some conditions in certain circumstances.
There is now a great deal of research about using stem cell transplants for many other conditions. For example:
This means that the stem cells used for the transplant come from your own body. They are usually collected when you are free of any sign of disease (when you are in remission) following conventional chemotherapy or other treatments. The stem cells can be used soon after being collected. They can also be frozen, stored and used in the future if needed. An autologous stem cell transplant is also called stem cell support, as the stem cells come from your own body. So, strictly speaking, it is not a transplant from a donor.
This means the stem cells used for the transplant come from someone else – a donor. This is often a close relative such as a brother or sister where there is a good chance of a close match. Unrelated donors are sometimes matched to people needing a transplant.
Stem cells can be collected:
It is very similar to a blood transfusion. Following the intense course of chemotherapy (and sometimes radiotherapy), the solution containing stem cells is given into one of your veins via a drip. The stem cells travel through your bloodstream and end up in your bone marrow. Here they start to make blood cells.
It can take several weeks for your bone marrow to recover, to take up the transplanted stem cells, and to make enough new blood cells. During this time you will need to be in hospital and be closely monitored. You may need several blood transfusions during this time until you are making enough blood cells. Antibiotic medicines are given to minimise the risk of infection. Also, medicines are given to help the stem cells to multiply as quickly as possible.
There is a risk of serious problems with a stem cell transplant. For example:
Your specialist will discuss with you the risks and possible side-effects of a stem cell transplant.
Posted: at 1:43 pm
Stem cell transplant replaces a persons blood-forming (hematopoietic) stem cells. It is used when stem cells or the bone marrow has been damaged by chemotherapy drugs, radiation therapy or disease (such as cancer). The new stem cells make healthy blood cells.
Stem cells are young, immature cells. Stem cells mature (through a process called differentiation) to become different types of specialized cells. They can copy (replicate) themselves to replace or rebuild tissues in the body. Some stem cells mature into blood cells. Blood-forming stem cells develop into different types of blood cells in the bone marrow. When blood cells are mature, they move from the bone marrow into the bloodstream.
Stem cell transplants use blood-forming stem cells from the bone marrow and blood circulating in the body (peripheral blood) in adults. They may also use blood-forming stem cells from the umbilical cord (the cord that supplies a developing fetus with blood and nutrients). Sometimes a stem cell transplant may be described by the source of the stem cells. Stem cell transplant is also called:
There are 3 main types of stem cell transplants. They are described based on who donates the stem cells.
Both children and the family have questions and concerns about when stem cell transplant is done. Sometimes having a stem cell transplant can cause physical or psychological distress to children and their families. Being prepared and knowing what to expect can reduce anxiety for both children and parents. Parents can prepare children for and help them cope with a stem cell transplant by explaining what will happen in a way that the child will understand.
Read the rest here:
Stem cell transplant – Canadian Cancer Society
Posted: October 25, 2015 at 2:46 pm
Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood. It may be autologous (the patient’s own stem cells are used) or allogeneic (the stem cells come from a donor). It is a medical procedure in the field of hematology, most often performed for patients with certain cancers of the blood or bone marrow, such as multiple myeloma or leukemia. 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.
Hematopoietic stem cell transplantation 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, such as autoimmune diseases.
Indications for stem cell transplantation are as follows:
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 and Hodgkin’s disease. More recently non-myeloablative, “mini transplant(microtransplantation),” procedures have been developed that require smaller doses of preparative chemo 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.
A total of 50,417 first hematopoietic stem cell transplants were reported as taking place worldwide in 2006, according to a global survey of 1327 centers in 71 countries conducted by the Worldwide Network for Blood and Marrow Transplantation. Of these, 28,901 (57 percent) were autologous and 21,516 (43 percent) were allogeneic (11,928 from family donors and 9,588 from unrelated donors). The main indications for transplant were lymphoproliferative disorders (54.5 percent) and leukemias (33.8 percent), and the majority took place in either Europe (48 percent) or the Americas (36 percent). In 2009, according to the World Marrow Donor Association, stem cell products provided for unrelated transplantation worldwide had increased to 15,399 (3,445 bone marrow donations, 8,162 peripheral blood stem cell donations, and 3,792 cord blood units).
Autologous HSCT requires the extraction (apheresis) of haematopoietic stem cells (HSC) 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 function 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 (graft-versus-host disease) is very rare 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.
However, for others cancers such as acute myeloid leukemia, the reduced mortality of the autogenous relative to allogeneic HSCT may be outweighed by an increased likelihood of cancer relapse and related mortality, and therefore the allogeneic treatment may be preferred for those conditions. Researchers have conducted small studies using non-myeloablative hematopoietic stem cell transplantation as a possible treatment for type I (insulin dependent) diabetes in children and adults. Results have been promising; however, as of 2009[update] it was premature to speculate whether these experiments will lead to effective treatments for diabetes.
Allogeneics HSCT involves two people: the (healthy) donor and the (patient) recipient. Allogeneic HSC donors must have a tissue (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 there is a good match 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. 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 mouth swab to see if they are a potential match. A “savior sibling” may be intentionally selected by preimplantation genetic diagnosis in order 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.
A compatible donor is found by doing additional HLA-testing from the blood of potential donors. The HLA genes fall in two categories (Type I and Type 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.
As of 2013[update], there were at least two commercialized allogeneic cell therapies, Prochymal and Cartistem.
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 human leukocyte antigens (HLA) as the recipient. About 25 to 30 percent of allogeneic HSCT reci
pients have an HLA-identical sibling. Even so-called “perfect matches” may have mismatched minor alleles that contribute to graft-versus-host disease.
In the case of a bone marrow transplant, the HSC 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 general anesthesia.
Peripheral blood stem cells are now the most common source of stem cells for allogeneic 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.
It is also possible to extract stem cells from amniotic fluid for both autologous or heterologous use at the time of childbirth.
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 HSC than is normally found in adult blood. However, the small quantity of blood obtained from an Umbilical Cord (typically about 50 mL) makes it more suitable for transplantation into small children than into adults. Newer techniques using ex-vivo expansion of cord blood units or the use of two cord blood units from different donors allow cord blood transplants to be used in adults.
Cord blood can be harvested from the Umbilical Cord of a child being born after preimplantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) matching (see PGD for HLA matching) in order to donate to an ill sibling requiring HSCT.
Unlike other organs, bone marrow cells can be frozen (cryopreserved) for prolonged periods without damaging too many cells. This is a necessity with autologous HSC because the cells must be harvested from the recipient months in advance of the transplant treatment. In the case of allogeneic transplants, fresh HSC are preferred in order 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 HSC, a preservative, DMSO, 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. HSC may be stored for years in a cryofreezer, which typically uses liquid nitrogen.
The chemotherapy or irradiation given immediately prior to a transplant is called the conditioning regimen, the purpose of which is to help eradicate the patient’s disease prior to the infusion of HSC and to suppress immune reactions. The bone marrow can be ablated (destroyed) with dose-levels that cause minimal injury to other tissues. In allogeneic transplants a combination of cyclophosphamide with total body irradiation is conventionally employed. This treatment also has an immunosuppressive effect that prevents rejection of the HSC by the recipient’s immune system. The post-transplant prognosis often includes acute and chronic graft-versus-host disease that may be life-threatening. However, in certain leukemias this can coincide with protection against cancer relapse owing to the graft versus tumor effect.Autologous transplants may also use similar conditioning regimens, but many other chemotherapy combinations can be used depending on the type of disease.
A newer treatment approach, non-myeloablative 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.:320321 Instead, non-myeloablative 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. Also significantly, while requiring high doses of immunosuppressive agents in the early stages of treatment, these doses are less than for conventional transplants. 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 allows donor T-cells to eradicate the remaining recipient HSC 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 and therefore 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.
After several weeks of growth in the bone marrow, expansion of HSC and their progeny is sufficient to normalize the blood cell counts and re-initiate the immune system. The offspring of donor-derived hematopoietic stem cells 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.
HSCT is associated with a high treatment-related mortality in the recipient (1 percent or higher), which limits its use to conditions that are themselves life-threatening. Major complications are veno-occlusive disease, mucositis, infections (sepsis), graft-versus-host disease and the development of new malignancies.
Bone marrow transplantation usually requires that the recipient’s own bone marrow be destroyed (“myeloablation”). Prior to “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. 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. For this reason transplant patients must be re-vaccinated with childhood vaccines once they are off immunosuppressive medications.
Severe liver injury can result from hepatic veno-occlusive disease (VOD). Elevated levels of bilirubin, hepatomegaly and fluid retention are clinical hallmarks of this c
ondition. There is now a greater appreciation of the generalized cellular injury and obstruction in hepatic vein sinuses, and hepatic VOD has lately been referred to as sinusoidal obstruction syndrome (SOS). Severe cases of SOS are associated with a high mortality rate. Anticoagulants or defibrotide may be effective in reducing the severity of VOD but may also increase bleeding complications. Ursodiol has been shown to help prevent VOD, presumably by facilitating the flow of bile.
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.
Graft-versus-host disease (GVHD) is an inflammatory disease that is unique to allogeneic transplantation. It is an attack of the “new” bone marrow’s immune cells against the recipient’s tissues. This can occur even if the donor and recipient are HLA-identical because the immune system can still recognize other differences between their tissues. It is aptly named graft-versus-host disease because bone marrow transplantation is the only transplant procedure in which the transplanted cells must accept the body rather than the body accepting the new cells. Acute graft-versus-host disease typically occurs in the first 3 months after transplantation and may involve the skin, intestine, or the liver. High-dose corticosteroids such as prednisone are a standard treatment; however this immuno-suppressive treatment often leads to deadly infections. Chronic graft-versus-host disease may also develop after allogeneic transplant. It is the major source of late treatment-related complications, although it less often results in death. In addition to inflammation, chronic graft-versus-host disease may lead to the development of fibrosis, or scar tissue, similar to scleroderma; it may cause functional disability and require prolonged immunosuppressive therapy. Graft-versus-host disease is usually mediated by T cells, which react to foreign peptides presented on the MHC of the host.
Graft versus tumor effect (GVT) or “graft versus leukemia” effect is the beneficial aspect of the Graft-versus-Host phenomenon. For example, HSCT patients with either acute, or in particular chronic, graft-versus-host disease after an allogeneic transplant tend to have a lower risk of cancer relapse. This is due to a therapeutic immune reaction of the grafted donor T lymphocytes against the diseased bone marrow of the recipient. This lower rate of relapse accounts for the increased success rate of allogeneic transplants, compared to transplants from identical twins, and indicates that allogeneic HSCT is a form of immunotherapy. GVT is the major benefit of transplants that do not employ the highest immuno-suppressive regimens.
Graft versus tumor is mainly beneficial in diseases with slow progress, e.g. chronic leukemia, low-grade lymphoma, and some cases multiple myeloma. However, it is less effective in rapidly growing acute leukemias.
If cancer relapses after HSCT, another transplant can be performed, infusing the patient with a greater quantity of donor white blood cells (Donor lymphocyte infusion).
Patients after HSCT are at a higher risk for oral carcinoma. Post-HSCT oral cancer may have more aggressive behavior with poorer prognosis, when compared to oral cancer in non-HSCT patients.
Prognosis in HSCT varies widely dependent upon disease type, stage, stem cell source, HLA-matched status (for allogeneic HCST) and conditioning regimen. A transplant offers a chance for cure or long-term remission if the inherent complications of graft versus host disease, immuno-suppressive treatments and the spectrum of opportunistic infections can be survived. In recent years, survival rates have been gradually improving across almost all populations and sub-populations receiving transplants.
Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror et al., using the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). The HCT-CI was derived and validated by investigators at the Fred Hutchinson Cancer Research Center (Seattle, WA). The HCT-CI modifies and adds to a well-validated comorbidity index, the Charlson Comorbidity Index (CCI) (Charlson et al.) The CCI was previously applied to patients undergoing allogeneic HCT but appears to provide less survival prediction and discrimination than the HCT-CI scoring system.
The risks of a complication depend on patient characteristics, health care providers and the apheresis procedure, and the colony-stimulating factor used (G-CSF). G-CSF drugs include filgrastim (Neupogen, Neulasta), and lenograstim (Graslopin).
Filgrastim is typically dosed in the 10 microgram/kg level for 45 days during the harvesting of stem cells. The documented adverse effects of filgrastim include splenic rupture (indicated by left upper abdominal or shoulder pain, risk 1 in 40000), Adult respiratory distress syndrome (ARDS), alveolar hemorrage, and allergic reactions (usually expressed in first 30 minutes, risk 1 in 300). In addition, platelet and hemoglobin levels dip post-procedure, not returning to normal until one month.
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 mononuclear cells of normal donors. There is evidence that myelodysplasia (MDS) or acute myeloid leukaemia (AML) can be induced by GCSF in susceptible individuals.
Blood was drawn peripherally in a majority of patients, but a central line to jugular/subclavian/femoral veins may be used in 16 percent of women and 4 percent of men. Adverse reactions during apheresis were experienced in 20 percent of women and 8 percent of men, these adverse events primarily consisted of numbness/tingling, multiple line attempts, and nausea.
A study involving 2408 donors (1860 years) indicated that bone pain (primarily back and hips) as a result of filgrastim treatment is observed in 80 percent of donors by day 4 post-injection. This pain responded to acetaminophen or ibuprofen in 65 percent of donors and was characterized as mild to moderate in 80 percent of donors and severe in 10 percent. Bone pain receded post-donation to 26 percent of patients 2 days post-donation, 6 percent of patients one week post-donation, and
In one metastudy that incorporated data from 377 donors, 44 percent of patients reported having adverse side effects after peripheral blood HSCT. Side effects included pain prior to the collection procedure as a result of GCSF injections, post-procedural generalized skeletal pain, fatigue and reduced energy.
A study that surveyed 2408 donors found that serious adverse events (requiring prolonged hospitalization) occurred in 15 donors (at a rate of 0.6 percent), although none of these events
were fatal. Donors were not observed to have higher than normal rates of cancer with up to 48 years of follow up. One study based on a survey of medical teams covered approximately 24,000 peripheral blood HSCT cases between 1993 and 2005, and found a serious cardiovascular adverse reaction rate of about 1 in 1500. This study reported a cardiovascular-related fatality risk within the first 30 days HSCT of about 2 in 10000. For this same group, severe cardiovascular events were observed with a rate of about 1 in 1500. The most common severe adverse reactions were pulmonary edema/deep vein thrombosis, splenic rupture, and myocardial infarction. Haematological malignancy induction was comparable to that observed in the general population, with only 15 reported cases within 4 years.
Georges Math, 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 Vina Nuclear Institute, but all of these transplants were rejected. Math later pioneered the use of bone marrow transplants in the treatment of leukemia.
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 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 complication called graft-versus-host disease.
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. 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.
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. 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 USA (8.0 million), and the highest number per capita were those from Cyprus (15.4 percent of the population).
Within the United States, racial minority groups are the least likely to be registered and therefore 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.
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. Many people belonging to different races are requested to donate as there is a shortage of donors in African, Mixed race, Latino, Aboriginal, and many other communities.
In 2007, a team of doctors in Berlin, Germany, including Gero Htter, performed a stem cell transplant for leukemia patient Timothy Ray Brown, who was also HIV-positive. From 60 matching donors, they selected a [CCR5]-32 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 1000 people of European ancestry have this inherited mutation, but it is rarer in other populations. 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. Levels of HIV-specific antibodies have also declined, leading to speculation that the patient may have been functionally cured of HIV. However, scientists emphasise that this is an unusual case. 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.
In 2012, Daniel Kuritzkes reported results of two stem cell transplants in patients with HIV. They did not, however, use donors with the 32 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). However, the virus was once again detected in both patients some time after the discontinuation of therapy.
Since McAllister’s 1997 report on a patient with multiple sclerosis (MS) who received a bone marrow transplant for CML, there have been over 600 reports of HSCTs performed primarily for MS. These have been shown to “reduce or eliminate ongoing clinical relapses, halt further progression, and reduce the burden of disability in some patients” that have aggressive highly active MS, “in the absence of chronic treatment with disease-modifying agents”.
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Hematopoietic stem cell transplantation – Wikipedia, the …
Posted: October 24, 2015 at 3:47 am
Doctors in Italy announced they have used patients’ own stem cells to grow trachea tissue that led to seemingly successful transplanted windpipes in two patients diagnosed with trachea cancer.
Doctors regenerated tissue from the patients’ nose and bone marrow stem cells to create tracheas biologically identical to the patients’ original organs. Both patients underwent the transplant in early July and were released from the hospital just weeks after the surgery, according to the Associated Press.
“They are back to the home, able to speak, able to socialize with everybody,” Giovannini told the Associated Press. “Having this quality of life is wonderful.”
According to Dr. Mark Iannettoni, head of the department of cardiothoracic surgery at University of Iowa, a trachea is a fragile organ because it is mostly cartilage, which has a poor blood supply.
“Once damaged, it is difficult to get it to heal correctly,” said Iannettoni.
Trachea cancer is resistant to chemotherapy and radiation and attempts to replace the trachea with mechanical devices have not been effective.
However, Dr. Eric Lambright, surgical director of lung transplant at Vanderbilt University Medical Center, said that using a patient’s own stem cells not only could help to rebuild the fragile tissue, but also potentially could bypass the risk of having the organ rejected.
“These patients [are] otherwise sentenced to rather significant horrible quality of life related to their tumors and … heroic measures may indeed be very appropriate,” said Lambright.
According to Macchiarini, the team collected stem cells from the patients’ nose and bone marrow, and grew two different types of tissues from the cells that resembled the different surfaces of the trachea. The tissues covered the outer and inner linings of the donor trachea.
Although these were the first stem cell transplants Macchiarini performed on trachea cancer patients, this is not the first trachea transplant of its kind. In 2008, Macchiarini and his surgical team successfully performed a trachea transplant using adult stem cells on a woman who suffered from tuberculosis.
The team transplanted a new windpipe with tissue grown from her own stem cells and did not need to administer anti-rejection drugs, according to the case report, published in the December 2008 Lancet.
While the procedure seemed to have worked in a few patients, many experts said the method is still in the earliest stages of development.
“This is a research project and not a proven therapy,” said Dr. Larry Goldstein, director of the stem cell program at University of California San Diego. “There’s an important step from innovative therapy to the research needed to bring the innovative therapy to a large number of people.”
In fact, Goldstein said there’s a lot more information needed to know exactly how the procedure worked. The hospital did not release the patients’ identities or more details about their cases due to privacy concerns, the Associated Press reported.
While this procedure was seemingly successful in a small number of patients, Lambright said it is still early to tell if the procedure works for a larger number of patients.
“We are a long ways away from knowing whether or not any of this has real durable application,” said Lambright.
Still, Goldstein said this latest procedure builds on the innovative work by Macchiarini to find a treatment for an otherwise fatal disease.
“It’s potentially very exciting,” said Goldstein. “The goal for this entire field is to generate new organs and replacement organs, and this is a step in the right direction.”
Iannettoni said this procedure could pave the way for other challenging transplants including the heart valve and the esophagus.
“The possibilities are endless once we unlock the potential for bioengineering,” said Iannettoni.
Successful Stem Cell Trachea Transplant – ABC News
Posted: at 3:47 am
An experimental treatment that uses a patient’s own stem cells may offer new hope for people with multiple sclerosis.
In a small clinical trial, patients experienced long-term disease remission after undergoing a transplant of their own hematopoietic stem cells. This type of cell is responsible for the formation of blood in the body and are typically derived from bone marrow. The patients also took high-dose immunosuppressive drugs.
The paper, published Monday in JAMA Neurology, reports on the third year of a five-year study. A total of 24 patients with active relapsing-remitting MS were enrolled in the trial. With this type of MS, patients have points when their disease is active followed by periods when they do not experience any symptoms.
Dr. Jon LaPook goes inside the trial and approval process for an experimental treatment using stem cells designed to make Multiple Sclerosis pati…
The researchers found that nearly 79 percent of the patients who underwent the procedure sustained full neurologic function for the three years following the treatment and symptoms of their disease did not progress. Additionally, patients in that time period did not develop any new lesions related to their disease.
More than 90 percent of patients did not experience disease progression, while 86 percent did not have any periods of relapse. Though a small number of patients did have side effects from the immunosuppressive drugs, they were no different than the side effects typically experienced by MS patients taking the drugs who haven’t undergone stem cell therapy.
“Longer follow-up is needed to determine the durability of the response,” the authors write in the study. “Careful comparison of the results of this investigation and other ongoing studies will be needed to identify the best approaches for high-dose immunosuppressive therapies for MS and plan the next clinical studies.”
The authors of an accompanying editorial say the research indicates this type of therapy has potential to work on patients who do not experience disease remission with medications alone, such as immunosuppressive drugs and anti-inflammatory drugs such as corticosteroids.
However, they add that “the jury is still out regarding the appropriateness and indication” of stem cell transplants for MS patients. Stem cell therapy is not approved by the U.S. Food and Drug Administration for the treatment of MS. The National Multiple Sclerosis Society currently funds 15 research projects on stem cell therapies that have the potential to prevent disease activity and repair nerve damage.
“Stem cell transplant for multiple sclerosis (MS) has been a subject of great interest to scientists, physicians, and patients,” the editorial notes. “The status of stem cell therapy is a common question posed by patients at their annual MS visit.”
MS is a progressive disease that damages the central nervous system. It affects about 250,000 to 300,000 people in the U.S., and 2.3 million worldwide. It is classified as an autoimmune condition, in which a person’s own immune system attacks myelin, that fatty coating that covers and protects nerves of the spine and brain.
Symptoms of MS can range from mild to severe, and may include numbness and tingling, loss of vision, chronic fatigue, balance and coordination problems, and sometimes a decline in memory and thinking skills. Sometimes damage from the disease can be permanent and lead to disability such as paralysis. Though there is no cure for this chronic condition, treatment for the disease has come a long way.
In the last few years a number of new drugs for MS have been approved by the FDA that have expanded options for a disease that often robs a person of essential functioning and disrupts quality of life. There are currently 12 FDA-approved drugs on the market that reduce symptoms and slow progression of the disease. Some have been found to also reverse nerve damage.
Advances in genomics have also provided new clues for how best to treat and manage the disease. In 2011, scientists completed the largest gene study to date that compared DNA from nearly 10,000 people with MS to DNA from more than 17,000 healthy individuals. The researchers were able to confirm 23 previously known genetic links and identified 29 genes and five genes that contribute to MS.
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Posted: October 19, 2015 at 10:49 pm
Stem cell transplantis used to facilitate high-dose chemotherapy. Stem cell therapy does not fight cancer. It helps the body recover after the high-dose chemotherapy which is used to treat cancers including multiple myeloma, non-Hodgkin’s lymphoma, Hodgkin’s disease and relapsed testicular cancer.
Standard chemotherapy Before high-dose chemotherapy and stem cell transplantation are used, medical oncologists administer multiple cycles of standard chemotherapy over several months. The standard chemotherapy is used to either reduce residual cancer cells or to determine if the patient will benefit from high-dose chemotherapy and stem cell transplantation.
Evaluation The first step in the high-dose chemotherapy/stem cell transplant process is a thorough evaluation to determine the patient’s likelihood of benefiting from the treatment.
Medical records The patient’s medical records are reviewed. Previous chemotherapy results, scans and other factors are considered to determine if the patient is likely to benefit from high-dose chemotherapy and stem cell transplantation. At this time the doctor will order other tests to establish whether the patient is physically able to go through the high-dose chemotherapy and stem cell transplant process.
MUGA scan or echocardiogram These tests measure how well the patient’s heart pumps blood.
A MUGA (MUltiple Gated Acquisition) scan uses a radioactive substance injected into the patient’s bloodstream and a gamma camera to produce a moving image of the heart as it beats.
An echocardiogram uses ultrasound to produce a moving image of the heart. It is similar to sonograms used to form images of babies in the womb.
Electrocardiogram (EKG) Electrocardiograms use sensors placed on various parts of the body to chart the heart’s electrical activity.
CT or PET scan CT (computed tomography) makes multiple x-rays scans and assembles them together to form very accurate images of structures within the body. Sometimes a contrast dye is injected to enhance clarity and definition. CT scans can determine location of tumors precisely.
PET (positron emission tomography) uses a radioactive material injected into the body and a gamma camera to detect the metabolic activity of cells. PET scans are not as precise at determining tumor location, but are extremely accurate at establishing tumor activity.
Frequently a combination PET/CT scan is used to simultaneously determine tumor location and activity.
Pulmonary function test A Pulmonary function test (or PFT) determines how much air is taken into the lungs when the patient inhales, how much is let out with each exhale and how quickly breath is exhaled. This helps doctors determine whether there any problems with the patient’s lungs.
Chest x-ray Chest x-rays are used to evaluate lung condition.
Blood tests Blood tests are used to determine if the patient’s liver and kidneys are functioning properly. Blood is also tested for previous infection and for exposure to viruses including hepatitis and HIV.
Bone marrow aspirate and biopsy In some cases a bone marrow aspirate and biopsy is needed to evaluate the bone marrow for disease. In this procedure a local anesthetic is used as a needle is inserted into the pelvic bone and a sample of marrow and bone tissue is withdrawn for biopsy.
Fertility considerations Since high-dose chemotherapy can cause infertility in both women and men, patients who are considering having children in the future are counseled about the risks of infertility and possible variations in treatment that may preserve fertility. In cases in which there are no possible variations patients may want to consider reproductive options such as egg harvesting or sperm banking.
Mobilization of stem cellsThe patient’s bone marrow must produce and release an unusually large number of stem cells before the stem cells can be collected. Patients are given medications to increase stem cell production and release. Calcium supplements are given for a few days prior to stem cell harvesting to minimize the effect of calcium loss which occurs during stem cell harvesting.
Harvesting stem cells An apheresis catheter is inserted into a large vein in the patient’s shoulder. (The port-a-cath which some patients may have had inserted for standard chemotherapy is not large enough for stem cell collection.)
The apheresis catheter isinserted under anesthesia at Fort Sanders Regional Medical Center, across the street from Thompson Cancer Survival Center.
Stem cells are harvested at Thompson Cancer Survival Center in three- to four-hour sessions every day until enough stem cells have been collected. It usually takes one to four days to collect enough stem cells.
In the stem cell harvesting process blood is removed from the patient’s body, circulated through an aspheresis machine and returned to the patient’s body. The aspheresis machine separates out the stem cells and retains them in plastic bags. Although all of the patient’s blood goes through the aspheresis machine several times in each session, only about one-half cup is inside the machine at one time.
Stem cell harvesting is an outpatient procedure, and a nurse is present during the entire procedure.Blood counts are monitored, and blood pressure and pulse rate are checked before and after the procedure.
The patient must sit or lie still throughout the procedure, and may feel dizzy, light-headed, cold or numb around the lips or fingertips.
Processing and storing stem cells The frozen stem cells are put into a liquid nitrogen freezer where they are preserved until time for transplantation.The bags of collected stem cells are taken to Thompson’s stem cell processing laboratory where the stem cells are counted and examined to be sure they are not damaged and that they are sterile.
Next the stem cells are mixed with a preservative called DMSO. Then the bags of cells are placed in aluminum containers and put into a slow-rate freezer where they are gradually taken to a temperature of -90.
The frozen stem cells are put into a liquid nitrogen freezer where they are preserved until time for transplantation.
High-dose chemotherapy High-dose chemotherapy (also called conditioning chemotherapy) is administered over a one- to six-day period, depending on the patient’s specific diagnosis.
Whenever possible, high-dose chemotherapy therapy is given on an outpatient basis at Thompson Cancer Survival Center. When inpatient high-dose chemotherapy is necessary it is done under the supervision of Thompson physicians at Fort Sanders Regional Medical Center.
Like all chemotherapy, high-dose chemotherapy may have side effects. These will vary depending on the medicines used for the patient’s specific cancer. A Thompson physician and nurse discuss the probable side effects of high-dose chemotherapy with each patient.
Transplantation of stem cells After high-dose chemotherapy, patients rest for a day or two to allow the drugs to be cleared from their systems.
Patients receive stem cell transplants either as outpatients at Thompson Cancer Survival Center or as inpatients at Fort Sanders Regional Medical Center. In either case, the process is the same:
Until engraftment occurs, patients are susceptible to infections (because of the lack of white blood cells), bleeding (because of lack of platelets) and fatigue (because of lack of red blood cells).
The transplant team watches the patient closely while waiting for engraftment. Anti
biotic, antiviral and antifungal medicines are given to the patient during this period to prevent infections.
After the engraftment is complete the patient can gradually return to normal activities. Initially exposure to infection should be avoided. The transplant team provides complete guidelines.
When patients return home, their personal physician, and medical oncologists resume caring for them. These doctors are kept fully informed of all aspects of patient care during the high-dose chemotherapy/stem cell transplant process, so they are completely aware of their patients’ conditions and any special medical needs.
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The Stem Cell Transplant Process – Covenant Health
Posted: October 12, 2015 at 11:46 am
A stem cell transplant poses many risks of complications, some potentially fatal. The risk can depend on many factors, including the type of disease or condition, the type of transplant, and the age and health of the person. Although some people experience few problems with a transplant, others may develop complications that may require treatment or hospitalization. Some complications could even be life-threatening.
Complications that can arise with a stem cell transplant include:
Your doctor can explain your risk of complications from a stem cell transplant. Together you can weigh the risks and benefits to decide whether a stem cell transplant is right for you.
If you receive a transplant that uses stem cells from a donor (allogeneic stem cell transplant), you may be at risk of graft-versus-host disease (GVHD). This disease happens when the donor stem cells that make up your new immune system see your body’s tissues and organs as something foreign and attack them.
GVHD may happen at any time after your transplant. However, it’s more common after your marrow has started to make healthy cells. Many people who have an allogeneic stem cell transplant get GVHD at some point. The risk of GVHD is a bit greater with unrelated donors, but it can happen to anyone who gets a stem cell transplant from a donor.
There are two kinds of GVHD: acute and chronic. Acute GVHD usually happens earlier, during the first months after your transplant. It typically affects your skin, digestive tract or liver. Chronic GVHD typically develops later and can affect many organs.
GVHD signs and symptoms include:
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Stem cell transplant Risks – Mayo Clinic
Posted: at 11:46 am
A bone marrow transplant, alsoknown as a haemopoietic stem cell transplant, replaces damaged bone marrow with healthy bone marrow stem cells.
Bone marrow is aspongytissue found in the hollow centres of some bones. It contains specialist stem cells, which produce the body’s blood cells.
Stem cells in bone marrow produce three important types of blood cells:
Bone marrow transplants are often needed to treat conditions thatdamage bone marrow. If bone marrow is damaged, it is no longer able to produce normal blood cells. The new stem cells take over blood cellproduction.
Conditions that bone marrow transplants are used to treat include:
Read more about why a bone marrow transplantis needed.
A bone marrow transplant involves taking healthy stem cells from the bone marrow of one person and transferring them to the bone marrow of another person.
In some cases, it may be possible to take the bone marrow from your own body. This is known as an autologous transplantation. Before it is returned, the bone marrow is cleared of any damaged or diseased cells.
A bone marrowtransplant has five stages. These are:
Having a bone marrow transplant can be an intensive and challenging experience. Many people take up to a year to fully recover from the procedure.
Read more about what happens during a bone marrow transplant.
Bone marrow transplants are usually only recommended if:
Read more about who can have a bone marrow transplant.
Bone marrow transplants arecomplicated procedures with significant risks.
In some cases, the transplanted cells (graft cells) recognise the recipient’s cells as “foreign”and try to attack them. This is known as graft versus host disease (GvHD).
The risk of infectionis alsoincreased because your immune system is weakened when you’re conditioned (prepared) for the transplant.
Read more about the risks of having a bone marrow transplant.
It’s nowpossible to harvest stem cells from sources other than bone marrow.
Peripheral blood stem cell donation involves injectinga medicine into the donor’s blood thatcauses the stem cells to moveout of the bone marrow and into the bloodstream where theycan be harvested (collected).
The advantage of this type of stem cell donation is that the donor doesn’t needa general anaesthetic.
Stem cells can also be collectedfrom the placenta and umbilical cord of a newborn baby and stored in a laboratory until they’re needed.
Cord blood stem cells are very usefulbecause they don’t need to be as closely matched as bone marrow or peripheral blood stem cells for a successful outcome.
Find out more about theNHS Cord Blood Bank(external link).
Page last reviewed: 18/02/2014
Next review due: 18/02/2016
Bone marrow transplant – NHS Choices
Posted: September 25, 2015 at 7:49 pm
About stem cell transplants
Stem cell transplant is a treatment to try to cure some types of cancer, such as leukaemia, lymphoma and myeloma. You have very high doses of chemotherapy, sometimes with whole body radiotherapy. This has a good chance of killing cancer cells but also kills the stem cells in the bone marrow. We need stem cells in order to make red blood cells, white blood cells and platelets. Doctors can collect stem cells from your blood or a donor’s. After high dose treatment you have the stem cells into your vein through a drip.
You have injections of growth factors before, and sometimes after, the stem cell transplant. Growth factors are natural proteins that make the bone marrow produce blood cells. You have them as small injections under the skin for between 5 and 10 days. Sometimes you may have low doses of a chemotherapy drug too. The chemotherapy and growth factor injections help your bone marrow to make lots of stem cells. These stem cells then spill out of the bone marrow into the bloodstream, where they can be collected.
Collecting the stem cells takes 3 or 4 hours. You lie down on a couch. Your nurse puts a drip into each of your arms and attaches it to a machine. Your blood passes out of one drip, through the machine and back into your body through the other drip. The machine filters the stem cells out of your blood. The stem cells are frozen until you are ready to have them back.
If you have stem cells from another person, you will have blood tests and the donor will also have blood tests. These tests make sure that the donated stem cells closely match your own.
Cord blood transplants use stem cells taken from the umbilical cord after a baby is born. A lower volume of stem cells are collected and so these are often used for children needing a transplant. But it may be possible for adults to have stem cells from 2 umbilical cords (double cord transplant).
Mini transplants are also called reduced intensity conditioning transplants. They use lower doses of chemotherapy than a traditional stem cell transplant. So they are used if people are not fit or well enough for a standard transplant.
View a summary of the bone marrow and stem cell transplant section
See more here:
Stem cell transplants | Cancer Research UK