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by Dr. C.D. Buckner M.D. Medically reviewed by C.H.Weaver M.D. 10/2021

High-dose chemotherapy and allogeneic bone marrow or blood stem cell transplantation is a treatment strategy that utilizes the administration of high doses of anti-cancer drugs and/or radiation therapy for the purpose of killing cancer cells and transplantation of stem cells to “rescue” or restore bone marrow blood and immune cell production. Transplantation is the term for transfer of tissue (a graft) from one person to another. Allogeneic is the term for a tissue graft from one person to another.

There are many types of allogeneic grafts that can be transplanted from one person to another, including skin, heart, kidney, liver, etc. However, the easiest organ in the body to transplant is the bone marrow. This is because a small quantity of stem cells taken from the bone marrow or peripheral blood of one person can repopulate the entire bone marrow organ of another person. In contrast to other types of transplants, the donor does not “miss” the small amount of bone marrow stem cells removed. A small quantity of bone marrow contains stem cells that are capable of dividing rapidly and repopulating the entire blood and immune system of another person within a short period of time.1-4

Stem Cell Transplant CancerConnect

High-dose chemotherapy and allogeneic stem cell transplantation is a component of an overall treatment strategy utilized to treat many kinds of cancers and blood disease. Allogeneic stem cell transplant has through various refinements continues to become more effective and safe. A recent analyses of patients treated at Fred Hutchinson Cancer Center showed that patients treated between 2013 and 2017 had improved survival and were less likely to suffer significant side effects that those undergoing transplant 10 years previously.4

Allogeneic 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. The timing of stem cell transplantation in the management of a specific cancer should be carefully planned following an initial diagnosis of cancer.

Cancers Treated with alloSCT

High-dose chemotherapy and allogeneic stem cell transplantation is the best 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 other cancers. The results achievable with high-dose chemotherapy for the treatment of specific cancers have been published and best describe the role of stem cell transplantation for the following cancers:

Learn more about allogeneic stem cell transplantation and the role it may play in the treatment of your cancer...

  • Selecting a Transplant Program
  • Donor Selection
  • Stem Cell Collection
  • Side Effects of Transplant

Stem Cell Center & Program Selection

A stem cell center consists of designated inpatient and outpatient treatment facilities with doctors and nurses experienced in stem cell transplantation. Three decades of continuous technological improvement have allowed high-dose chemotherapy and stem cell transplantation to become safe and widely available. There are currently over 200 centers that provide high-dose chemotherapy and stem cell transplantation services in the United States, 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. Its important to select a program with expertise in treating your cancer and a proven track record of performing the procedure. When choosing a stem cell center, 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.

  • 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 mortality rates 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. In general, an unrelated donor transplant 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. On the other hand, many small autologous transplant centers produce equal or better outcomes than large centers. Take the time to evaluate all potential centers and choose the center, physician, staff and environment where you feel most comfortable receiving your treatment.

Stem Cell Transplant Newsletter

Donor Selection

Allogeneic stem cell transplant is the best, and occasionally the only, curative treatment option for certain cancers. For these patients, a timely search for the best available stem cell donor can be life-saving.

The goal of selecting a stem cell donor is to provide the best “match” between the donor and the patient (host). The body’s immune defense system consists of white blood cells that travel continuously throughout the body in surveillance of foreign substances or cells. They destroy what they perceive as “non-self”. When donor stem cells are transplanted into a new host, several donor-host interactions may occur. On one end of the spectrum, the host’s immune system may reject the donor’s cells (i.e., graft rejection or failure). On the other end, the donor’s cells may attack (reject) the recipient’s tissues in what is called graft-versus-host reaction.

Cells have surface antigens that can recognize and reject foreign tissues. These are called human leukocyte antigens or HLAs. Donors are selected on the basis of blood testing (tissue typing) for HLA antigens. The major HLA antigens determine tissue compatibility and are located on the 6th chromosome. Four sets of HLA antigens have so far been identified: A, B, C, D. To ensure the best possible acceptance of donor stem cells, it is best to match all of the four HLA antigen sites.

HLA Matched Family Members

Originally, donor and recipient were exclusively siblings who had inherited the identical 6th chromosomes from the father and mother. In this situation, all of the HLA antigens (and all other antigens) located on the 6th chromosome are identical between donor and recipient. However, in some instances a parent can be matched with a child or a child with a parent. In addition, if the mother and father have similar HLA antigens siblings can be a suitable matches without inheriting the same 6th chromosome. It is therefore important to test blood samples from the entire immediate family ,i.e., parents, siblings and children.

Haploidentical Donors

A transplant using stem cells from a donor whose HLA type is a half-match for the recipient is referred to as haploidentical. This alternative procedure called a haploidentical stem cell transplant is designed to provide the benefits of stem cell transplant with a lower risk of GVHD. In a haploidentical transplant, doctors transplant cells that aren’t an identical match. These “half matched” cells can come from family members. Parents and children are always a half match for each other, and siblings have a 50% chance of being a half match for each other. In addition to lowering the risk of GVHD compared with an unrelated allogeneic transplant, haploidentical transplants also helps doctors find potential donors more quickly.

Haploidentical stem cell transplants are increasingly used for individuals who have been unable to find a more closely matched donor. A recently published clinical trial in patients with acute myeloid leukemia (AML) has demonstrated that a haploidentical related donor stem cell transplant has resulted in similar survival as a transplant from an unrelated matched donor. Furthermore, transplant from a half matched donor appeared to lower the risk of graft-versus-host disease (GVHD).

To compare outcomes between haploidentical and allogeneic transplants, researchers studied both techniques in 192 patients with AML who underwent haploidentical transplant and 1,982 patients who underwent allogeneic transplant from a closely matched unrelated donor. Patients who received haploidentical transplants had a lower incidence of GVHD compared with the allogeneic treatment group with both myelablation and reduced intensity conditioning regimens. Survival outcomes between haploidentical and allogeneic transplants were mixed but fairly similar. On the one hand, patients in the haploidentical group who received myeloablative treatment had a slightly lower probability of three-year survival compared with allogeneic patients (45% versus 50%, respectively). On the other hand, patients in the haploidentical group with reduced intensity conditioning transplants had a slightly higher probable three-year survival at 46% versus 44%. This research may help patients for whom finding a matched unrelated donor is difficult as well as provide an option for stem cell transplant with lower risk of GVHD.

Unrelated Donors

More recently, there has been considerable success in using unrelated individuals as bone marrow or blood stem cell donors. An unrelated donor is obtained by a computerized search carried out by the National Marrow Donor Program (NMDP), which is sponsored by the National Institutes of Health. This search is initiated by the transplant center that will provide your treatment. You can get an immediate estimate of the probability of finding a donor for a given patient by using the “World Book,” which is a registry of all of the potential donors in the NMDP plus all of the other international unrelated donor banks. Your HLA type is submitted to this service by your transplant center at no cost and the number and location of potential donors is immediately available.5

This is helpful at the outset, as it provides you with important information about the likelihood of finding a donor and how long it will take. Once potential donors are identified by the NMDP, detailed blood testing has to be performed to confirm compatibility between donor and recipient. This requires obtaining blood samples from the patient and the prospective donor. Some donors will turn out not to be compatible on more extensive testing and some donors may be more compatible than others. This extensive testing makes identification of a donor a much longer procedure than that necessary to identify a family member donor.

The National Marrow Donor Program was established in the mid-1980’s and had less than 250,000 donors in 1990. Now with more than 5 million donors listed in the registry and thousands of transplants performed using unrelated donors provided by the NMDP. With the current number of donors in the registry, more than 70% of patients are able to find a suitable match. Donor identification is significantly lower for patients in racial minorities.

One limitation of the NMDP is the time it takes to locate a donor. The median time from initiation of a search to donor identification is now approximately 10 weeks, which is an improvement from the 6-month searches of the past. Therefore, it is important to initiate a search early in the disease course, especially for diseases that are rapidly progressive, such as the acute leukemias. Donors can be found more rapidly for patients with common HLA types than for patients with less common HLA types. Sometimes it is helpful to do a quick survey of donor availability by performing a “World Book” search as mentioned above.

Umbilical Cord Blood

Human umbilical cord blood (UCB) is a rich source of the stem and progenitor cells that are present in bone marrow. Cord blood from related and unrelated donors has been successfully transplanted in children and adults worldwide. Due to the relatively small number of cells infused per kilogram of body weight in adults however cord blood may need to be “expanded” in culture for adult transplants. In general, cord blood is utilized when no suitable family member or unrelated donor is available.

Parents can also have the cord blood cryopreserved at the time of delivery of a child. This has been useful when a prior child has a disease treatable by marrow or blood stem cell transplantation and there is no other donor available. Umbilical cord blood is cryopreserved in “cord blood banks”. HLA typing is performed and available for computer matching in the same way that the NMDP performs unrelated donor searches. Approved transplant centers are provided with the frozen cells when needed.

Stem Cell Collection

Following the delivery of high-dose therapy to patients 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, but more recently, many cancer centers have adopted the practice of collecting stem cells from peripheral blood

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 and then a surgeon inserts a large needle directly into the bone marrow cavity of bones of the lower back after the area 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 and 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.

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 where they 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 and several others are in development.