In an allogeneic transplant, a person's stem cells are replaced with new, healthy stem cells obtained from a donor or from donated umbilical cord blood. Chemotherapy or a combination of chemotherapy and radiation therapy is first given to eradicate cancer cells, to suppress the patient's immune system, or both. The new stem cells are then infused into the patient's bloodstream through an intravenous catheter, in a procedure that is similar to a blood transfusion.
Finding a Donor
Finding a suitable donor is critical for the success of an allogeneic transplant.
Become a Donor
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Because the immune system can distinguish between your body's own cells and cells that are foreign — and can destroy foreign cells — your donor's tissue type should match yours as closely as possible. If the tissue is not a close match, complications can result from the immune system's response to the transplant, which may be serious and difficult to treat.
In a condition called graft-versus-host disease (GVHD), for example, a donor's cells develop into white blood cells in a patient's bone marrow, but recognize the patient's own cells as foreign and attack them.
To avoid such complications, every effort is made to find a matched donor. This is done by a test called tissue typing, which is based on proteins called human leukocyte antigens (HLA) that are found on the surface of white blood cells and tissues.
Often the ideal donor is a patient's brother or sister who has inherited the same HLA. But only about one patient in four who could benefit from allogeneic transplant has this ideal donor. For the remaining 75 percent of patients, physicians expand the search to other family members, who may be only partially HLA matched, and to volunteer donor registries. In some cases, umbilical cord blood stored in public banks can be used as an alternative source of stem cells for allogeneic transplantation.
A major registry is the National Marrow Donor Program, which maintains a database of potential marrow donors and is linked with other national and international registries, creating a combined pool of close to 8 million potential donors. If you need a transplant and do not have a matching donor in your family, you can use information from your HLA typing lab report to search for potential donors. You can also search for cord blood units from the National Cord Blood Program.
Online searches may identify a number of potential matches, but only a transplant center can determine whether these potential matches are suitable and available. If you choose Memorial Sloan-Kettering Cancer Center to be your transplant center, we will work with you to evaluate matches. For more information, please call 212-639-7431.
Harvesting the Donor's Stem Cells
If you receive a transplant from a family member or from an unrelated donor, physicians will first collect or “harvest” the blood-forming stem cells from your donor's bone marrow or bloodstream.
Bone Marrow Donation
Bone marrow harvesting is performed in an operating room while the donor is under general anesthesia. The physician inserts a hollow needle into the rear and sometimes the front hipbone, both of which contain a large quantity of bone marrow. The breastbone is another accessible site that is rich in marrow, but this is very rarely used for harvest. The donor will not need stitches, but will have some pain and tenderness at the site of the harvest for about a week.
Until recently, stem cells were harvested only from the bone marrow. Today, physicians can also collect stem cells from a donor's circulating blood — known as peripheral blood stem cells (PBSCs) — using a procedure called pheresis. Unlike a bone marrow harvest, pheresis does not have to be done in an operating room, and the donor does not have to be under general anesthesia.
A few days before the procedure, donors are usually given a medication (G-CSF [filgrastim], GM-CSF [sargramostim], or a combination of the two) that makes stem cells leave the bone marrow and go into the circulating blood. These agents can cause flu-like symptoms and bone pain in the days before and after the procedure.
The pheresis procedure will take several hours over the course of two or three days. The blood passes through a tube inserted in one of the donor's veins and then through a machine that separates stem cells from other blood cells, which are then returned to the patient. The stem cells collected during the procedure are either used immediately or are frozen and stored.
Preparing for the Transplant
When a donor's stem cells are available, patients receiving an allogeneic transplant will go through a process known as the preparative regimen, conditioning, or cytotoxic therapy.
In this step, physicians use chemotherapy with or without radiation therapy to kill cancerous cells in the body. If given in high doses, the treatment can suppress the immune system by destroying blood-forming stem cells in the bone marrow, decreasing the risk that the patient's body will reject the donor's cells. Such intensive treatment, called myeloablative or high-dose therapy, is not suitable for all patients.
An alternative way of preparing for a transplant is to give lower doses of chemotherapy with or without low doses of radiation. In this type of treatment, called a non-myeloablative or “mini” transplant, patients are also given drugs that suppress their immune system without destroying stem cells.
For patients who receive radiation therapy in addition to chemotherapy, Memorial Sloan-Kettering researchers have developed a less intensive radiation treatment called hyperfractionated radiation. This approach involves giving small doses of radiation to the whole body, or to the parts of the body containing lymph nodes, two to three times a day over several days, a week, or more. This reduces many of the side effects of more-intensive radiation therapy. Patients usually receive the transplant a day or two after their last chemotherapy or radiation dose.
Transplantation and Recovery
After the preparative regimen is complete, the transplant can begin. Physicians usually transplant the harvested stem cells by injecting them into the patient's bloodstream, in the same way that they would administer a blood transfusion. Over the following days and weeks, the transplanted stem cells migrate to the marrow space in the patient's bones, where they gradually begin to produce blood and immune system cells. The transplant can be given in a number of ways, depending on the patient's disease, available donors, and other factors.
Between two and three weeks after the transplant, physicians usually start to detect the donor's cells in the patient's bloodstream. As time passes, a successful transplant graft will produce red blood cells, white blood cells, and platelets.
During the days immediately after transplantation, patients need a great deal of medical support. You may receive transfusions of irradiated blood products, such as platelets and red blood cells, as well as antibiotics to prevent and treat bacterial, viral, and fungal infections, which are most likely to occur in the first three months after transplantation. Patients are also vulnerable to complications resulting from chemotherapy with or without radiation therapy, which may require additional treatments.
Most patients remain in the hospital for several weeks after the transplant. During this time, precautionary measures are taken to protect the patient from infection. All people who enter the room are required to wear protective gloves and masks, and to wash their hands with antiseptic soap. Sometimes people entering the room need to cover their clothing with clean, disposable gowns. Fresh fruit, flowers, plants, or cut flowers are prohibited, as these can carry disease-causing molds and bacteria.
Types of Allogeneic Transplantation
Unmodified Stem Cell Transplant
In an unmodified, or conventional, transplant, all the harvested bone marrow cells — including a type of immune cell called T cells — are infused into the patient without having been manipulated in the laboratory. These transplants are more appropriate for patients who are at risk of relapse and who can tolerate the medications required to prevent the complication known as graft-versus-host disease.
In T-cell-depleted transplants, the bone marrow cells harvested from a donor are first manipulated in the laboratory to remove T cells, which can cause graft-versus-host disease (GVHD) if transplanted into a patient. The remaining cells, including blood-forming stem cells, are then infused into the patient. New T cells will form in the patient from the donor's stem cells, but are less likely to cause disease than the donor’s existing T cells.
Because T-cell-depleted transplants have a lower risk of GVHD, this approach can be used in transplants between patients and donors whose tissue types (HLA) are not fully matched. Because this type of transplant can be easier to tolerate, it may be a possibility for older patients, even those over 60 years old, provided they are otherwise medically fit.
Cord Blood Transplants
In a cord blood transplant, the stem cells used have been collected from the umbilical cord and placenta of healthy newborns. Because the likelihood of graft-versus-host-disease after cord blood transplant is low, there is a decreased requirement for a very close tissue type (HLA) match between the patient and the newborn donor.
Cord blood can therefore be a good alternative stem cell source for patients without a matched unrelated donor, particularly for those requiring conventional (non-T-cell-depleted) transplants. Learn more about Memorial Sloan-Kettering's research on cord blood transplantation.
Donor Lymphocyte Infusions (DLI)
For patients with certain types of cancer whose diseases recur late after transplantation, physicians may treat the patient with gradually increasing numbers of T cells from the original donor. The low levels of T cells can eliminate the recurrent cancer without causing significant graft-versus-host disease.
Management of Complications
A number of complications might occur after an allogeneic transplant. Most of them can be prevented, managed, or treated.
Graft-versus-host disease (GVHD) can develop if white blood cells that have formed from the donor's stem cells recognize the patient's cells and tissues as foreign and attack them.
Dr. Sergio Giralt talks about the role of the immune response in bone marrow transplantation.
The lesser the match between a donor and a patient's tissue types (HLA), the greater the risk and severity of GVHD. Factors such as the age and gender of the patient and the donor, as well as the intensity of the chemotherapy with or without radiation therapy the patient receives before transplantation, also determine the risk of GVHD.
GVHD can be either acute or chronic. Symptoms of acute disease include skin rash and intestinal or abdominal discomfort, which is caused by an inflammation of the liver and the lining of the intestine. In patients with this condition, the rebuilding of the immune system may be delayed.
Your doctor may administer drugs such as methotrexate or cyclosporine to prevent acute GVHD from occurring. Drugs called steroids may also be given to control the condition if it develops.
Sometimes, the donor's stem cells fail to develop and replenish the patient's blood cells after the transplant. The most common cause of this complication, called graft failure, is that the patient's immune system recognizes the donor's cells as foreign and the body rejects them. This may occur if the chemotherapy with or without radiation therapy given before the transplant were not able to fully suppress the patient’s immune system.
Graft failure can also be caused by infections with certain viruses. Improved methods for prevention, early detection, and treatment of these infections are reducing graft failure caused by viral infections.
The risk of graft rejection generally lasts about two to four weeks after transplant, although it can occasionally develop at a later time. If graft failure occurs, your doctor may recommend transplanting more donor stem cells, if they are available.
Complications of High-Dose Therapy
Patients who have received high doses of chemotherapy or radiation therapy may develop acute or chronic complications — including infections, bleeding, and anemia — during the period before blood cell production returns to normal. Liver and lung problems can also develop after a transplant. Physicians have developed treatments for both acute and chronic side effects that help many patients.
Another possible complication is mucositis, a condition in which the cells that line the mouth and intestinal tract are destroyed by the high-dose chemotherapy and/or radiation therapy. Symptoms include mouth pain and ulcers, abdominal pain, diarrhea, and infection. A new drug called recombinant human keratinocyte growth factor (rHuKGF), which is being studied in clinical trials, is believed to reduce the duration of mucositis in transplant patients.
For some cancer patients — particularly those whose disease is in an advanced stage or has already relapsed when the transplant is initiated — there is a risk that their disease could come back after a transplant. This can happen if the chemotherapy with or without radiation therapy did not eradicate the cancer successfully.
At Memorial Sloan-Kettering, patients who have had a transplant are followed closely by their team of doctors, who watch for any signs of returning disease. If the cancer recurs, the doctors shift their treatment strategy.
In rare instances, patients may develop a secondary cancer or a noncancerous condition such as a myelodysplastic syndrome as a result of the high-dose treatment.