Carolyn Vachani RN, MSN, AOCN & Lara Bonner Millar, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 11, 2014
Bone marrow is a spongy substance found inside our large bones, such as the femur (thigh), hip, and ribs. It is made up of cells called hematopoietic stem cells. It is these cells that are given (transplanted) to the patient during a stem cell transplant. (NOTE: These stem cells are different than those we hear about in the news for research use- those are called embryonic stem cells.) Hematopoietic stem cells are "baby" cells that grow up to become either white blood cells, red blood cells and platelets. The bone marrow acts as a greenhouse for these cells, growing them and storing them until they are needed. What do we need them for?
Autologous means structures or cells derived from you and your body. For example, if our patient Jack is to have a stem cell transplant, we will get those stem cells from Jack himself. Many people think a transplant has to be something taken from a donor, but that would be called an allogeneic transplant (which is discussed in a separate article). In an autologous transplant, Jack the patient "donates" his cells to himself.
Autologous transplants are used to treat a number of different cancers, including leukemias, myelodysplastic syndrome, multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma, testicular cancer and neuroblastoma.
When doctors first started doing these procedures, the only way to get stem cells was directly from the bone marrow. This is where the term bone marrow transplant first originated. The patient would be taken to the operating room and put to sleep lying on his/her stomach. The doctors would put long needles into the hip bones and pull out the bone marrow in syringes in a procedure called bone marrow aspiration. The solution was then poured through a special column that pulled out only the stem cells, allowing any other cells (mature red and white blood cells and platelets) to be reinfused into the patient. In order to get the number of cells needed, the needles would need to be inserted many times. These cells were then frozen in a special preservative (called Dimethyl sulfoxide or DMSO) to protect them from "freezer burn" until they were used.
Doctors soon found that giving the patient a medication called granulocyte colony stimulating factor, or GCSF, would stimulate the stem cells to be released from the bone marrow and into the blood stream. Using a blood test, doctors could tell how many cells were circulating in the blood stream. Once the number was high enough, the patient would go to the pheresis department at the hospital to have the cells removed: this procedure is known as "apheresis."
The cells could be removed using either a catheter in the chest wall or 2 large intravenous (IV) catheters, one placed in each arm. Blood would be taken out of the patient, be circulated through the pheresis machine to remove the stem cells, and then the rest of the blood would be returned to the patient. The cells would be frozen in the same DMSO preservative as the bone marrow; cryopreservation is necessary because the cells must be harvested months in advance of the transplant treatment. During the collection, the patient may experience tingling or numbness around their lips. This is caused by a loss of calcium and can usually be resolved by eating some calcium tablets.
In order to understand the stem cell transplant, you must first have an understanding of chemotherapy. Chemotherapy is a group of medications that work by killing rapidly-dividing cells in the body. Cancer cells tend to divide rapidly, but so do many healthy cells (i.e. cells in the gastrointestinal tract, hair follicles, and blood cells). If you bite the inside of your lip, there is a good chance the spot will be healed by the next day. This is because those cells divide rapidly. A patient can only receive so much chemotherapy before the medication causes too much damage to the healthy cells for the person to safely tolerate. For instance, if a patient experiences a lot of diarrhea with a medication, the doctor may decide to decrease the dose by some amount. Doctors call this "dose-limiting toxicity." One important dose-limiting toxicity is low blood counts (low white blood cells, red blood cells and platelets). Researchers thought that for certain types of cancer, if they could give higher doses of chemotherapy, they would be better able to treat the cancer. The problem was, how could we overcome the dose-limiting toxicity of low blood counts?
Doctors soon realized that they could give high doses of chemotherapy that would wipe out a patient's bone marrow, but then later "rescue" the bone marrow using the patient's own stem cells (which were collected earlier, before the chemotherapy). The patient would receive several days of intense chemotherapy aimed at killing any cancer cells in his/her body. The patient then rests for 1 or 2 days to allow the body time to process and clear out the chemotherapy, so the new cells are not damaged.
On the day of the "transplant", the patient is given some medications to prevent him/her from having any reactions to the DMSO preservative. The patient receives intravenous fluids to help the kidneys flush out any dead cells in the infusion. Blood pressure and heart rate are closely monitored. Once the patient has received the premedications, the frozen stem cells are thawed and given to the patient like a blood transfusion. Some centers thaw the cells in the lab where they are stored, while some thaw them in the patient's room just prior to infusing them into the bloodstream.
The cells are quite smart, and they find their way back to the bone marrow space and get to work. Remember, when the stem cells arrive in the bone marrow, things are in bad shape - almost all of the old marrow cells have been killed ("ablated") by the chemo. The stem cells get right to work and produce new white and red blood cells and platelets. It can take anywhere from 7 to 14 days for the stem cells to produce new cells, and for those new cells to mature enough to function.
This waiting period, also called the "nadir," is the most difficult time for the patient. The blood cell counts are very low, putting the patient at risk for infections, bleeding, and severe fatigue. The patient does not have any white blood cells to fight infections, so fevers and the need for antibiotics are to be expected. All visitors and healthcare personnel must wash their hands before entering the room. Anyone who is sick or lives with someone who is sick would be best to stay home and call on the phone. Low platelet counts can lead to bleeding, and platelet transfusions are common during this time. A low red blood cell count (called anemia) may be most distressing for the patient. The patient may look pale, feel tired, and require red blood cell transfusions. Many patients say the worst side effect is the extreme fatigue - they feel more tired and wiped out than you can even imagine. Just getting out of bed is a chore. When able, short walks in the halls can actually increase their energy, but this is often easier said than done.
On top of the low blood counts, the patient must deal with the side effects of the chemotherapy drugs used. These include, diarrhea, nausea and/or vomiting, hair loss, fever, chills, decreased appetite, and mouth sores (called mucositis). Every patient is different and it is difficult to predict which patients will have more side effects. The chemotherapy drugs used before the transplant can vary, and some medications are more likely to cause certain side effects than others.
Be supportive, let the patient get a lot of rest, and understand that he or she just may not feel like eating much during this time. Make one family member the contact person for friends and family. Let the patient tell this contact person how he or she is feeling each day and whether or not he or she wants visitors or phone calls. It is important to respect the patient's wishes. Send a supportive note or a card. If the patient has children, knowing that friends or family are taking care of things like carpooling and school homework might be very comforting. Depending on the protocol for the transplant, the patient may be in the hospital, at an apartment near the cancer center, or at home.
Engraftment is a term the doctors use to describe the point when the stem cells start doing their job and blood cell counts start to come up. The first number we look for is the neutrophil count, which is the type of white blood cell that is most important in fighting infection. Generally, once the neutrophil count gets above 500, the patient can come off antibiotics and, in many cases, can go home. The time until engraftment varies from patient to patient, but is typically between 7-12 days. The red blood cell and platelet counts can take several weeks to get back to a normal range, but the patient can usually go home once they are not regularly requiring blood or platelet transfusions.
This can vary greatly from person to person, depending on what has happened over the past few weeks. It can take people weeks, months, or even a year to feel like their "old self" again. Some patients report having no appetite, or food tasting like metal, for months after the transplant. This can be a difficult time, as family and friends may assume that the person is "better" since they are home and the transplant is over. They may expect the person to be back at work, to return to school, or to run a household. The patient should resume normal activities slowly and add on jobs or duties every couple of days.
Abeloff M, Niederhuber JE, Armitage JO, Doroshow, JH, Kastan MB, Tepper, JE. Abeloff’s Clinical Oncology. 5th edition. Philadelphia: Churchill Livingstone; 2014.
May 11, 2012 - For patients with multiple myeloma, maintenance treatment with lenalidomide is associated with improved progression-free survival for newly-diagnosed patients ineligible for transplantation and for those who have undergone stem-cell transplantation, according to three phase 3 studies published in the May 10 issue of the New England Journal of Medicine.
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