by C.D. Buckner M.D. Medically updated by C.H.Weaver M.D. 5/2021
High-dose chemotherapy and autologous stem cell transplantation involves the administration of high doses of anti-cancer drugs and/or radiation therapy for the purpose of killing cancer cells, followed by the infusion of stem cells to “rescue” or restore bone marrow blood cell production. It is important to understand that high-dose chemotherapy is the treatment for your cancer and damage to the bone marrow is a side effect. Fortunately, the bone marrow can be “rescued” or replaced with stem cells. For autologous stem cell transplantation, stem cells are collected from the patient before high-dose chemotherapy is delivered. The stem cells are collected form the bone marrow or peripheral blood, processed, frozen and stored. Since these cells are collected from the patient, they are referred to as autologous stem cells and the term autologous stem cell transplantation refers to either bone marrow or peripheral blood stem cell transplantation.
High-dose chemotherapy and autologous stem cell transplantation is a component of an overall treatment strategy utilized to treat many types of cancer. High-dose chemotherapy and autologous stem cell transplantation may be appropriately utilized as the initial or subsequent treatment depending on the type of cancer. It is not a treatment of last resort and the role of stem cell transplantation in the management of a specific cancer should be carefully planned following an initial diagnosis of cancer.
Collection and Processing of Stem Cells
Following the delivery of high-dose chemotherapy for the treatment of cancer, infusion of stem cells is necessary to ensure recovery of bone marrow function and production of red blood cells, white blood cells and platelets. Historically, stem cells were harvested from bone marrow, however many cancer centers have recently adopted the practice of collecting stem cells from peripheral blood. Autologous stem cells must be collected, or harvested, from a patient prior to treatment with high-dose chemotherapy. The harvested stem cells are then frozen and can be stored for many years. Stem cells can also be processed in ways that remove cancer cells and/or attempt to activate immune cells in the stem cell collection for the purpose of treating the cancer.
Techniques of Stem Cell Collection Harvesting
The collection of stem cells from bone marrow has been safely performed for over 30 years. A bone marrow harvest is relatively simple and typically occurs in the operating room. During a bone marrow harvest, patients receive general anesthesia. A surgeon then inserts a large needle directly into the bone marrow cavity of bones of the lower back, which has been sterilized. Bone marrow is aspirated, or sucked, out of the bones by inserting the needle into the bone multiple times. A typical bone marrow harvest takes about two hours and involves the removal of one liter of bone marrow containing the stem cells. The major side effect of this procedure is discomfort at the site of the bone marrow harvest. Infrequent complications include bleeding, infection and nerve damage.
Peripheral Blood Stem Cell Harvesting
The collection of stem cells from the blood is slightly more complicated than collection from bone marrow. This procedure has been performed safely for over a decade. Collecting stem cells from the peripheral blood may also have several clinical advantages compared to collecting them from bone marrow. The main advantage of peripheral blood stem cells over bone marrow is that enough peripheral blood cells can be collected to support several courses of high-dose chemotherapy. This may have significant advantages for treatment of several blood cancers as well as solid tumors such as breast cancer.
Stem cells normally circulate in the blood in very small quantities and can be collected from the blood through a small catheter inserted into a patient’s vein. The number of circulating stem cells in the blood is increased in patients whose bone marrow is recovering from chemotherapy. Cytokines (blood cell growth factors) administered to patients after myelosuppressive chemotherapy can also cause a 100-fold increase in the number of stem cells circulating in the blood. Injection of cytokines stimulates increased production of immature and mature bone marrow stem cells and their release into the blood. Once released into the blood, stem cells can be collected. Cytokines can also be administered without chemotherapy and cause a substantial increase in the number of circulating blood stem cells for collection. The process of delivering a cytokine or growth factor with or without myelosuppressive chemotherapy for the purpose of collecting stem cells is referred to as stem cell mobilization. Two cytokines, Neupogen® and Leukine®, stimulate the bone marrow’s production of stem cells and are approved by the Food and Drug Administration for use in patients to increase the number of circulating stem cells. Several other cytokines are in development.
During stem cell mobilization, patients receive an injection of a cytokine and are evaluated daily. The process of actually collecting the stem cells from the blood is called apheresis—this begins when there are sufficient stem cells circulating in the blood for collection. Stem cells are collected with an apheresis machine from the blood flowing through a catheter, which is inserted into a vein. Blood flows from a vein through the catheter into the apheresis machine, which separates the stem cells from the rest of the blood and then returns the blood to the patient’s body. Apheresis is performed for several days until enough stem cells have been collected to support treatment with high-dose chemotherapy.
Stem cells can be reliably identified and accurately measured because they have a specific marker or label on the stem cell surface. This marker is referred to as the CD34 antigen. Measuring the number of CD34 antigen-positive stem cells is important because doctors can accurately predict how fast the bone marrow recovers after high-dose chemotherapy administration based on the number of CD34-positive stem cells infused. Daily measurement of the CD34+ peripheral blood stem cell content is also useful in determining the number of days to perform apheresis.
An optimal number of stem cells to support rapid bone marrow recovery and blood cell production after treatment with high-dose chemotherapy is approximately 5 million CD34+ cells/kg patient weight. Infusion of over 5 million cells/kg results in the majority of patients recovering bone marrow blood cell production in only nine to10 days. The minimal number of stem cells necessary to ensure safe recovery of bone marrow blood cell production is currently unknown. Patients who do not have enough stem cells harvested can undergo stem cell mobilization a second or third time. In the majority of cases, patients will and have enough stem cells to perform a transplant. If peripheral blood stem cells are harvested early in the disease course, sufficient stem cells can be collected to support multiple treatment courses.
Bone Marrow or Peripheral Blood Stem Cells?
Today, virtually all autologous stem cell transplants are performed with peripheral blood stem cells collected after mobilization with chemotherapy and Neupogen® or with Neupogen® alone. This is because peripheral blood stem cells are easier to harvest and result in more rapid recovery of blood cell counts.
Selecting an Autologous Transplant Center
Physicians and centers performing autologous stem cell transplants should have designated inpatient and outpatient treatment facilities with doctors and nurses experienced in performing stem cell transplantation. Continuous technological advances have made high-dose chemotherapy and autologous stem cell transplantation safe, and widely available in most clinics including large cancer centers, community hospitals and physician practices. The increased availability of stem cell transplants to patients has allowed many patients to benefit from this treatment approach who otherwise could not have traveled away from their family and support system. When choosing where to be treated with high-dose chemotherapy and autologous stem cell transplant, the following objective criteria may be useful in selecting a center:
Center Volume: The American Society of Blood and Marrow Transplant (ASBMT) recommends that a center perform at least 10 transplants in the previous year to maintain proficiency.
Quality of Staff: The ASBMT recommends that each center have a transplant team that includes a “program director” and at least one other physician experienced in transplant medicine. The director should be board certified and have 2 years experience or 1 year training in transplant medicine. You may also want to know which physician will actually provide your care. Will it be the program director, other physicians, or fellows (doctors in training)? The continuity of nursing care is also important, since the majority of care is actually delivered by the nurses. A single coordinating nurse can be invaluable. You may want to ask which nurses will be involved with your care and how frequently they will change.
Continuity of Care: Will a single or multiple doctors oversee your care during and after the high-dose chemotherapy treatment? If you are leaving your primary doctor to receive your care at a transplant center, it is important to know whether you can receive all your care and follow up at the transplant center. If not, then how well does that center communicate with your primary doctor concerning your long-term treatment plan and management of potential complications. Many patients prefer to receive their treatment close to home with a single doctor to ensure good continuity of care.
Outcomes: Evaluating the actual treatment results may be the most useful criteria when selecting where to receive treatment. The ASBMT recommends that each center keep accurate patient records that include specific treatment outcome information. Asking the following questions may help you choose one center over another.
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- What are the cure and survival rates for patients treated in the center with your specific cancer?
- What is the average duration of hospital stay?
- What are the outcomes reported by the center?
Patient Satisfaction: Ask to talk with a patient who has been treated in the center, as well as to see the results of patient satisfaction surveys. All good centers can arrange for a new patient to talk to other patients that have been previously treated at the center.
Facility Infrastructure: The ASBMT recommends that facilities where high-dose chemotherapy is delivered have designated inpatient and outpatient areas, standard policies regarding infection control and the ability to evaluate patients on a 24-hour basis. Programs should also have a stem cell processing capability and 24-hour blood bank support. Accreditation of stem cell processing facilities began in 1997 and is currently being performed by the American Association of Blood Banks (AABB) and the Foundation for Accreditation of Hematopoietic Cell Therapy (FAHCT).
Allogeneic vs. Autologous: Lastly, the type of transplant being performed may also dictate where you choose to receive treatment. Allogeneic unrelated donor transplants requires more infrastructure and experience to perform than a matched sibling allogeneic transplant or an autologous transplant. Some of the largest centers performing unrelated donor transplants produce the best outcomes for patients. Take the time to evaluate all potential centers and choose the center, physician, staff and environment where you feel most comfortable receiving your treatment.
Cancers Treated with Autologous Stem Cell Transplantation
High-dose chemotherapy and autologous stem cell transplantation is the most effective treatment for certain cancers because it improves survival and cures more patients than other treatments. High-dose chemotherapy is currently being evaluated in controlled clinical trials for the treatment of several types of cancers. Published results best describe the role of stem cell transplantation in the treatment of the following cancers:
- Acute Myelogenous Leukemia
- Multiple Myeloma
- Hodgkin's Lymphoma
- Non-Hodgkin Lymphoma
- Breast Cancer and other Solid Tumors
Complications or Side Effects of Autologous Stem Cell Transplantation
Patients undergoing ASCT may experience a range of predictable and well understand side effects that can be effectively managed. Its important to report all possible side effects to your transplant doctors and nurses.
The safety of autologous transplant has improved a great deal thanks to advancements in supportive care to manage potential side effects. While high doses of chemotherapy and radiation therapy can potentially affect any of the body’s normal cells or organs, the more common side effects are well described and include the following which patients and caregivers should watch for and report to their transplant team.
The nature and severity of the side effects from high-dose chemotherapy and autologous stem cell transplantation are directly related to the type of high-dose chemotherapy treatment regimen used and are further influenced by the condition and age of the patient.
Bone Marrow Suppression
High-dose chemotherapy directly destroys the bone marrow’s ability to produce white blood cells, red blood cells and platelets. Patients experience side effects caused by low numbers of white blood cells (neutropenia), red blood cells (anemia) and platelets (thrombocytopenia). Patients usually need blood and platelet transfusions to treat anemia and thrombocytopenia until the new graft beings producing blood cells. The duration of bone marrow suppression can be shortened by infusing an optimal number of stem cells and administering growth factors that hasten the recovery of blood cell production.
During the two to three weeks it takes the new bone marrow to grow and produce white blood cells, patients are susceptible to infection and require the administration of antibiotics to prevent bacterial and fungal infections. Bacterial infections are the most common during this initial period of neutropenia. Stem cells collected from peripheral blood tend to engraft faster than bone marrow and may reduce the risk of infection by shortening the period of neutropenia. The growth factor Neupogen® (filgrastim) also increases the rate of white blood cell recovery and has been approved by the Food and Drug Administration for use during autologous stem cell transplant.
The immune system takes even longer to recover than white blood cell production, with a resulting susceptibility to some bacterial, fungal and viral infections for weeks to months. After initial recovery from autologous stem cell transplant, patients are often required to take antibiotics for weeks to months to prevent infections from occurring. Prophylactic antibiotic administration can prevent Pneumocystis carinii pneumonia and some bacterial and fungal infections. Prophylactic antibiotics can also decrease the incidence of herpes zoster infection, which commonly occurs after high-dose chemotherapy and autologous stem cell transplant.
Sinusoidal Obstructive Syndrome (SOS)-Veno-Occlusive Disease of the Liver (VOD)
High-dose chemotherapy can result in damage to the liver, which can be serious and even fatal. This complication is increased in patients who have substantial amounts of previous chemotherapy and/or radiation therapy, a history of liver damage, or hepatitis. Sinusoidal Obstructive Syndrome of the liver typically occurs in the first two weeks after high-dose chemotherapy treatment. Patients typically experience symptoms of abdominal fullness or swelling, liver tenderness, and weight gain from fluid retention. A new drug called defibrotide has has shown some promise in treating patients with SOS, defibrotide is currently available in Europe and is being evaluated in clinical trials in the United States.
Interstitial Pneumonia Syndrome (IPS)
High-dose chemotherapy can directly damage the cells of the lungs. This may be more frequent in patients treated with certain types of chemotherapy and/or radiation therapy given prior to the transplant. This complication of transplant may occur anytime, from a few days after high-dose chemotherapy to several months after treatment. This often occurs after a patient has returned home from a transplant center and is being seen by a local oncologist.
Patients typically experience a dry non-productive cough or shortness of breath. Both patients and their doctors often misinterpret these early symptoms. Patients experiencing shortness of breath or a new cough after autologous transplant should bring this to the immediate attention of their doctor since this can be a serious and even fatal complication.
Graft failure is extremely unusual in autologous stem cell transplantation. Graft failure occurs when bone marrow function does not return. The graft may fail to grow in the patient—resulting in bone marrow failure—with the absence of red blood cells, white blood cells and platelet production. This results in infection, anemia and bleeding. Graft failure may also occur in patients with extensive marrow fibrosis before transplantation, a viral illness or from the use of some drugs (such as methotrexate). In leukemia patients, graft failure often is associated with a recurrence of cancer; the leukemic cells may inhibit the growth of the transplanted cells. In some cases, the reasons for graft failure are unknown.