The Stem Cell Transplant Process
Stem cell transplantation is a complex process that may take months to complete. Your doctors, nurses, and the transplant coordinator will review information about your child's stem cell transplant during the consent meeting, daily rounds, and visits to the clinic. The following links will provide you with a general description of the stem cell transplantation process:
Children eligible for stem cell transplantation will have several preliminary appointments for tests and blood work scheduled before being admitted for transplant. These pre-transplant evaluations and appointments will be scheduled by our Transplant Coordinator who acts as your advocate throughout the pre-transplant work up. You will also meet with your attending physician to discuss the plan for your child in depth and to sign the transplant consent form.
If your child is receiving an autologous (self) peripheral blood stem cell transplant, we will collect their stem cells before admitting your child for transplant. Most often, stem cells are collected in the BMTU inpatient clinic. Stem cell collection is coordinated with the Transplant Coordinator. Often there is the need to first place a large catheter or central line into the large blood vessel in the leg (femoral vein) so that the stem cells can be adequately collected. It may take one or two days to collect enough stem cells for a transplant.
Conditioning therapy, or myeloablative preparative therapy, refers to the high-dose chemotherapy and/or radiation that children receive before they receive their stem cell infusion. These treatments have side effects. They will destroy the child's bone marrow and weaken the immune system, however, from a transplant perspective, these are positive consequences. This will make room in the bone marrow for the new cells to take hold and will also suppress the immune system which helps to keep the body from rejecting the new cells. The day your child receives the bone marrow or stem cells is called Day Zero (Day 0). The days prior to Day 0 are the days that a patient receives the conditioning therapy (or chemotherapy). These days are referred to with negative numbers, for example Day -7, Day -6, Day -5, etc.
The goals of conditioning therapy are to kill cancer cells in the body in patients with a malignant disorder and to kill the normal cells in the marrow cavities of the bones so the new marrow will have room to grow. If your child is receiving cells from another person, conditioning therapy has a third goal which is to suppress your child's immune system so it will not reject the donor's cells
Day 0: Stem cell infusion
Day 0 is the day the stem cells are infused. Stem cells are infused through the child's central venous line. It is similar to having a blood transfusion.
Expected side effects
After Day 0, the days are referred to with positive numbers, for example Day +1, Day +2 or Day +3. Patients may begin to have some of the expected side effects from the conditioning therapy such as nausea, vomiting, diarrhea, and mouth sores.
Infections after transplant
Stem cell transplant patients are at high risk for infections because the immune system is suppressed from the conditioning therapy. Patients who receive stem cells from another person have an additional risk for infection since they will also take medications that suppress the new immune system. Patients need these immunosuppressive medicines in order to help prevent graft-versus-host disease (GVHD).
After the infusion, the child will be watched very closely to make sure the new stem cells are settling into the marrow and beginning to manufacture new blood cells (called engrafting). Lab work will be checked daily to follow this process. After the marrow has been infused, the number of white blood cells and neutrophils, a certain type of white blood cell, will increase over the next two to four weeks.
Engraftment occurs when the stem cell graft is making enough neutrophils to offer some protection against bacterial and other types of infections.
On average, engraftment takes an average of 2 weeks, but it can happen as quickly as 1 week or take as long as 6 weeks. Your child will receive medicines to promote engrafting and to prevent rejection and graft-verses-host disease.
Full engraftment may take several months, and prior to that, patients may require regular blood and platelet transfusions. In some cases, the graft does not fully take, and if this occurs, the doctors may elect to change certain medications or even give more stem cells to the patient.
If your child receives stem cells from someone else (an allogeneic transplant), there is a risk of graft-versus-host disease (GVHD). GVHD may occur before or after the new stem cells engraft. It occurs when the immune cells from the donor transplant recognize the recipient's body tissues as foreign and attack them. This happens because the donor's T lymphocytes (a type of white blood cell) from the graft or transplant react against the cells of the patient (or host). Therefore, the condition is called graft (from the donor)-versus-host (the patient) disease. The symptoms of GVHD are usually seen in the skin, the gastrointestinal tract (digestive system), and the liver. Many patients develop some degree of GVHD, and for leukemia, there is an advantage in getting GVHD as this can lessen the risk of the leukemia coming back (called graft vs. leukemia effect).
The incidence and severity of GVHD increase with greater mismatching between the patient and donor's HLA typing. Patient and donor characteristics like age and gender, as well as how strong the chemotherapy given before transplant is, all play roles in the likelihood that a patient will or will not develop GVHD.
GVHD can be either acute or chronic. In general, acute GVHD occurs before Day +100 and chronic GVHD occurs after Day +100. Symptoms of acute GVHD include a skin rash and intestinal and abdominal discomfort caused by an inflammation of the liver and the lining of the intestine. For patients with this condition, the rebuilding of the immune system may be delayed. Treatment to prevent acute GVHD can include methotrexate, mycophenylate, cyclosporine, or related drugs. There are many medications used to control the condition when it develops, though the most important drug would be steroids.
A bone marrow or stem cell graft "fails" when the patient does not recover marrow function after the transplant. Grafts generally fail because the patient rejects donor cells. The donor stem cells will initially engraft but later fail to produce enough healthy blood cells. Most cases of graft failure occur within the first two months after transplant though in some cases in may occur within the first year of transplant. Infections, especially from certain viruses, can cause graft failure. Improved methods for prevention, as well as early detection and treatment of these infections, are reducing graft failure caused by viral infections.
Other side effects
The conditioning therapy and medications used during transplant may cause other side effects and toxicities which will be discussed with you by your transplant doctors. Our doctors and nurses will explain these problems, and the recommended treatments, if they occur. Blood tests, x-rays, CAT scans, MRI scans, ultrasounds or biopsies (tissue samples) of certain tissues may help in the diagnosis of such problems.
Kids who receive stem cell transplants have a high risk of infection because during conditioning therapy and while the transplant is engrafting, their immune systems are weakened and unable to fight bacteria and other germs that enter the body. Children who receive an allogeneic transplant have an even greater risk of infection because they require medications to suppress their immune systems even more to reduce the chance of rejection and graft versus host disease.
Because of these risks, a child who's had a stem cell transplant will not be released from the hospital until doctors are sure the transplant has successfully engrafted and the child is otherwise doing well.
A child may be discharged after engraftment has occurred. He or she must also be medically stable and able to take the required medications.
Restrictions after Discharge
Once released, a child needs very close monitoring and follow-up care. Specific instructions will be given about when normal activities can resume. Autologous (self) transplant patients in general should not attend school or visit other public indoor places for three months after transplant. Allogeneic (related and unrelated donor) transplant patients should not attend school or visit indoor public places for nine to 12 months after transplant, depending on the patient's status. This is because for kids with a compromised immune system, even a simple infection like a common cold can be serious and even life-threatening if untreated. After a transplant, it can take 1 to 2 years for a patient's immune system to fully recover. Also, many times patients will continue to have central lines in place, and this predisposes them to serious infection. If a patient does develop a fever while a central line is still in place, this will require an admission to the hospital to receive appropriate treatments and antibiotics. You will receive information at the time of discharge about the precautions that you should take and when you should call the doctor.
The stress of having a child who is being treated for any type of cancer can be overwhelming for a family. That stress can be magnified when treatment requires a long "isolation period," as is necessary with a stem cell transplant.
To find out about support and resources that may be available for you, your child, or your family, talk to your nurse, your doctor, a hospital social worker, or child life specialist. Many resources are available that can help you get through this difficult time.