IBMT: FAQ - Allogeneic Stem Cell Transplant Process

Allogeneic Stem Cell Transplant Process

You are considered a potential candidate for an allogeneic stem-cell transplant. This pamphlet will try to explain the why and how of such a procedure.

Why A Stem Cell Transplant?

Most patients undergoing an allogeneic stem-cell transplant have a malignant disease that is sensitive to chemotherapy. It is hoped that administering a much higher dose of chemotherapy will result in a better chance of your cancer remaining in remission. A long remission will ultimately lead to a cure for many patients.

To treat your cancer more intensively, high doses of chemotherapy are needed. Radiation of a part of your body, or of your entire body (TBI = Total Body Irradiation), may also be part of the treatment. Both the high-dose chemotherapy and the radiation will suppress and damage your bone marrow. Inside the bone marrow reside stem cells, which are the "mother" cells that can produce all the cells that are found in your blood: red cells, platelets, and white cells. Without stem cell transplant, high-dose chemotherapy and/or radiation would lead to lengthy or permanent low levels of red cells, platelets, and white cells. Consequent risks would include anemia, bleeding, and infection. A stem cell transplant is performed to restore the stem cells, which in turn will produce sufficient white cells, platelets, and red cells to protect you. At the same time, the new stem cells may start fighting your cancer.

Other indications for an allogeneic transplant are non-cancerous diseases of the bone marrow, such as aplastic anemia, sickle cell anemia, thalassemia, inborn metabolic diseases, and diseases of the immune system.

Why An Allogeneic Stem Cell Transplant?

For your specific disease, your physicians feel that the use of your own stem cells would be less beneficial than the use of stem cells from a donor. Many factors are considered when selecting an autologous or an allogeneic stem cell transplant. In general, autologous stem cell transplants are safer and simpler than allogeneic (donor) stem cell transplants. Autologous transplants rely completely on the ability of the chemotherapy and radiation ("preparative regimen") to kill the cancer cells, and need healthy stem cells that can be collected from the patient (“autos” means “self” in ancient Greek). Allogeneic stem cells come from healthy donors, and thus have not been exposed to chemotherapy and are never contaminated with cancer cells. Since the donor and the recipient are different (“allos” means “other”), immunological differences exist. The new stem cells may attack the tissues of the patient (graft-versus-host disease), but they may also attack the cancer (graft-versus-leukemia effect). Thus, while more difficult, allogeneic transplants are potentially able to attack cancer more effectively than autologous transplants.

For What Diseases Are Allogeneic Stem Cell Transplants Used?

leukemia (acute myelogenous, acute lymphocytic, chronic myelogenous, chronic lymphocytic)
malignant lymphoma and Hodgkin's disease
multiple myeloma
myelodysplastic syndrome
myeloproliferative disorder
severe aplastic anemia
immunodeficiencies
hemoglobin disorders (sickle cell anemia, thalassemia)

Who Is Going To Be The Donor?

The best donor is a sibling (brother or sister) who is HLA-type (tissue type) identical with the patient. When a patient has one sibling, the chances of having a matched donor are 25%. Other relatives may be possible donors, but the risks of such transplants are clearly higher than in the HLA-identical sibling situation. If more than one HLA-identical sibling is available, the preference will be for male donors or for female donors who have not been pregnant. Previous exposure to a certain common virus (CMV) may also be a factor in the selection of a donor.

For patients who do not have a suitable related donor, registries of volunteer (unrelated) donors exist. In this country, The National Marrow Donor Program (NMDP) is the largest registry. IBMT is a transplant center for the NMDP. World-wide, about 7 million volunteer donors have been registered.

The preferred sequence for selection of possible donors for IBMT physicians is:

HLA-identical sibling donor
HLA-matched unrelated donor
HLA-matched umbilical cord cells
mismatched related donor

For information on being a stem cell donor, see The Donor Experience page.

Bone Marrow Or Peripheral Blood Stem Cells?

Donor stem cells can come either from the bone marrow, or from the peripheral blood. Several factors are considered when making the decision which stem-cell source to use. For some donors, bone marrow harvest may be more difficult. In general though, donor bone marrow is preferred by IBMT for patients with a low to average risk of relapse of their disease and for matched unrelated transplants. Peripheral blood stem cells are used in case of a mismatched related donor, and for patients at high risk of disease relapse. Peripheral blood stem cells are also preferentially used for non-myeloablative transplants.

Cells from umbilical cord blood may also be used, but this stem-cell source presents several unique problems. Hematologic recovery is often delayed, making prolonged support with platelet transfusions necessary.

How Is An Allogeneic Stem Cell Transplant Done?

Once you have completed the pre-transplant process and evaluation, and your donor has been cleared for stem cell donation, the actual transplant episode starts. Often patients are admitted to the Bone Marrow Transplant Unit (6 Tower) of St. Francis Hospital and Health Centers (in Beech Grove, IN) at the start of the preparative regimen, but increasingly part of this phase is done as an outpatient.

Upon arrival on the transplant unit, your nurse will explain your room to you and obtain a short history. Then your labwork will be drawn and necessary X-rays will be arranged. If you don't already have a central line (Hickman^®, Groshong^®, or Permcath; see the Linecare page), one will be inserted in Interventional Radiology, or in the Operating Room.

Once admitted, you will stay in a HEPA-filtered room, to decrease the risk of infection. HEPA stands for “High Efficiency Particulate Air” and means that a filter removes all germs from the passing air. In these rooms, the ceiling of the room contains this highly efficient filter through which all the air enters the room. As long as your white cells are low, you stay in this isolation, but family and friends can visit with you while wearing clean gloves and a face-mask. Visiting hours are from 12 noon to 12 midnight. As long as you are in isolation, you will also have diet restrictions, again to prevent infections. You should not eat fresh fruits or vegetables, or food from outside the hospital. You will use bottled drinking water. As additional measures to decrease the risk of infection, you should not have flowers or plants in your room.

Depending upon the disease and the type of donor, either 3 days of radiation (TBI) are given, followed by 2-8 days of chemotherapy, or only 6 days of chemotherapy are used. The irradiation is given twice a day for a total of six doses. The chemotherapy consists of a combination of drugs. Your IBMT physician will discuss with you which drugs will be used, and give you a calendar outlining precisely which drugs will be given and when. Most chemotherapy drugs are given by intravenous infusion. Many additional drugs will be administered during the days of radiation and chemotherapy. Some are meant to prevent nausea from chemotherapy, some to prevent infections, others to prevent complications from the chemotherapy drugs. Many are given by mouth, some are given by vein. You will also receive lots of fluid by vein to help to remove waste products as rapidly as possible. The day before the stem-cell infusion you will start daily infusions of cyclosporine, a drug to try to prevent severe graft-versus-host disease.

Two days after the last chemotherapy, the stem cells will be infused over 2-3 hours through your central line. This infusion only rarely causes any side effects. After the infusion of stem cells, the wait is on for the growth of the new blood cells. It takes about 10-20 days before the first white cells re-appear. In the meantime, the "old" blood cells start dying off, and patients will become prone to infections and bleeding. They will almost certainly need multiple transfusions of platelets and red cells (see Blood Transfusion page). Once the white cells and platelets re-appear, they slowly return to the normal range. Transfusions are usually only needed for the first 3-6 weeks after transplant.

As a patient on the transplant unit, you will be expected to participate in your care as much as possible. You should take a daily shower, try to eat in spite of mouth sores, and stay active inside your room. You definitely should avoid spending the entire day in bed just "waiting to get better".

What Happens After Transplant?

Following an allogeneic stem cell transplant, most patients recover slowly. The mind tends to recover more rapidly than the body, and patients often become impatient with their progress. Before you leave the hospital, the nursing staff, pharmacist and physicians will discuss with you the routines of outpatient care. You will receive written information, and should ask about any aspect of which you feel uncertain. Half the patients leave the hospital by day 18 after transplant, but discharge does not mean that the process is over. Very frequent clinic visits are necessary, initially probably two or three times a week. During such clinic visits, infusions of drugs, fluids and electrolytes, and transfusion of blood products may be needed. At home, you still will take many medications. Among these are cyclosporine, antibiotics, magnesium, and vitamins. Complications (see below) are frequent, and may lead to readmission to the transplant unit. Slowly patients start feeling better and complications become less frequent. Your medication will be reduced, and your clinic visits less frequent. You may be able to go back to work 6 months after transplant, but if complications occur, 12 months is not uncommon.

What Complications May Occur?

An allogeneic stem cell transplant is a complex therapy and can give rise to a number of complications. The most important ones will be discussed here. Patients should realize that some patients develop no complications at all, whereas other patients may develop several. As a general rule, the better your clinical condition at the time of transplant, the fewer the complications.

Infections may occur at any time after transplant. Bacterial infections are most common when the white cells are low. Fungal infections may occur during this period with low white cells, and again if strong immuno-suppression is needed for graft-versus-host disease. Viral infections can occur early, but are most frequent between 2 and 6 months after transplant. Any infection is possibly serious, but most can be treated successfully with antibiotics. All patients will receive oral antibiotics to prevent infections. Many patients will also receive intravenous medications to prevent viral and fungal infections. This therapy will often continue until the immune system is less vulnerable.
Bleeding may occur when your platelets are low. While bleeding into the skin is not very serious, it may indicate a high risk for bleeding in other places. The most dangerous bleeding occurs inside the head, in the bowel, or in the lungs ("alveolar hemorrhage syndrome"). Platelets will be transfused to decrease the risk of bleeding (see Blood Transfusion page).
Hemorrhagic cystitis. If this complication occurs, the urine becomes bloody and urination is painful. It is caused either by Cytoxan, one of the chemotherapy drugs, or by a virus. When you receive Cytoxan, we always use Mesna, which decreases the risk of hemorrhagic cystitis. Once cystitis occurs, pain medication, lots of fluid, and a Foley catheter to continuously rinse your bladder may be required. This complication may last several weeks.
Veno-occlusive disease of the liver. In patients who receive high-dose chemotherapy, the small blood vessels in the liver may form clots, which make it difficult for the blood to flow through the liver. Patients show weight gain, pain in the liver area, free fluid in the abdomen ("ascites"), and jaundice (yellow skin). If this complication occurs, supportive care is the treatment, to give the liver time to repair itself. Some new treatments are being tried to prevent the clotting process.
Bone marrow rejection. Just like a transplanted kidney can be rejected, the donor stem cells can be rejected. This is quite rare when an HLA- identical sibling is the donor, but more frequent with unrelated or mismatched related donors. If rejection happens, the only possible treatment is to try to repeat the transplant. Since the patient will then be much longer without sufficient white cells, fatal infections may well occur. One of the most important purposes of the preparative regimen of chemotherapy and radiation is to prevent rejection.
Acute Graft-versus-Host disease. GvHD is the opposite of rejection. Instead of the patient trying to reject the new stem cells, the new stem cells try to reject the patient. The stem cells have the capacity to recognize the tissues of the patient as "different" and can attack them. Obviously, the better patient and donor are matched, the less chance of recognition as different. Thus, patients receiving unrelated or mismatched related stem-cell grafts are at higher risk of GvHD. In such cases, IBMT physicians try to remove cells which can cause GvHD (T-cells) from the circulating blood during and after stem cell infusion. Even patients receiving grafts from fully matched sibling donors will at least receive cyclosporine to decrease the risk of GvHD.If GvHD does occur, steroids (Solumedrol^®, prednisone) are the first line of therapy. These steroids will be tapered very slowly to prevent a flare of GvHD. See also Graft-versus-Host page.

If you have additional questions or concerns, we encourage you to discuss them with your IBMT physician, the clinic nurses, or the transplant coordinator.