Here we offer a review of bone marrow transplants and other types of stem cell transplants that are used to treat cancer. We outline what a transplant is like for. This section provides information on the following topics. A bone marrow transplant, also called a stem cell transplant, is a treatment for some types of cancer. For example, you might have one if you have leukemia.
Transplants Stem Cell
The time when your white blood cell and platelet counts are at the lowest is called your nadir. It is important for you to understand how your counts can affect your treatment, activity level, and infection exposure.
Learn what precautions you should take when your blood counts are low. White blood cells are responsible for fighting infection. Your normal white blood cell count is 4, to 10, There are three main types of white blood cells: Neutrophils, the most important infection-fighting cells, consist of "polys" and bands. The total number of polys and bands is referred to as the absolute neutrophil count ANC. When your ANC drops below — a condition called neutropenia — you are at greater risk for infection.
Your doctor may prescribe a colony-stimulating factor called G-CSF or GM-CSF to stimulate the production of cells in your bone marrow and help your white blood cell count recover more rapidly. When your ANC recovers, your risk of infection declines, but you may still be at risk for viruses and fungi.
It may take as long as one to two years before your immune system recovers completely. You can calculate your ANC by taking the total number of white blood cells and multiplying it by the percentage of polys. Red blood cells are responsible for carrying oxygen to cells throughout your body. Red blood cells are measured by values called hemoglobin Hgb and hematocrit Hct.
The normal value for hemoglobin is The normal value for hematocrit is 37 to If your red blood cell count is too low, this is called anemia. You may feel more tired or short of breath than usual. The next step is conditioning therapy. Sometimes the patient gets other types of medicines that don't kill the cells, but that weaken the immune system instead.
Wiping out unhealthy cells or weakening the immune system might sound scary. But it can be helpful. Destroying bone marrow makes room for new stem cells to take hold. And a weak immune system isn't as likely to jump into high gear and attack the new cells. So there's less chance that the body will reject the new cells.
The actual transplant is done through an infusion. This is when the stem cells are put in the patient's body through an IV line. Patients are closely watched after a stem cell infusion. The medical team will make sure the new stem cells settle into the bone marrow and begin to make new blood cells called engrafting.
Engrafting usually takes about 2 weeks, but can be as quick as 1 week or as long as 6 weeks. The medical team gives the patient medicines to promote engrafting and prevent problems. Going home doesn't mean going back to normal life right away. The risk of infection means that it might be 3 months or more before a child can go back to school, visit the mall, or go to a sporting event. That's because even a simple infection like a cold can be life-threatening for kids whose immune systems need time to recover.
Having a child being treated for cancer or another serious condition can be stressful for any family. 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. 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. 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.
Decreasing doses of immunosuppressive therapy then allow 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 [ citation needed ]. HSCT is associated with a high treatment-related mortality in the recipient 38 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 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.
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 condition. 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. The mucosal lining of the bladder could also be involved in approximately 5 percent of the children undergoing hematopoietic stem cell transplantation.
This causes hematuria, frequency, abdominal pain and thrombocytopnea . Graft-versus-host disease GVHD is an inflammatory disease that is unique to allogeneic transplantation. It is an attack by 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 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.
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. 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.
Mortality for allogeneic stem cell transplantation can be estimated using the prediction model created by Sorror et al. The risks of a complication depend on patient characteristics, health care providers and the apheresis procedure, and the colony-stimulating factor used G-CSF.
Allogeneic stem cell transplant
By now you have probably heard the terms 'stem cell transplant', 'bone marrow transplant' or 'haemopoietic stem cell transplant' mentioned a. A procedure in which a patient receives healthy blood-forming cells (stem cells) to replace their own that have been destroyed by disease or by the radiation or. Stem cells help rebuild a weakened immune system. Stem cell transplants are effective treatments for a wide range of diseases, including cancer.