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HEMATOPOIETIC CELL TRANSPLANTATION OVERVIEW — Hematopoietic cell transplantation (also called bone marrow transplantation or stem cell transplantation), is a type of treatment for cancer (and a few other conditions as well). A review of the normal function of the bone marrow will help in the understanding of stem cell transplantation.
Hematopoietic stem cell function — Bone marrow is the soft, spongy area in the center of some of the larger bones of the body. The marrow produces all of the different cells that make up the blood, such as red blood cells, white blood cells (of many different types), and platelets. All of the cells of the immune system are also made in the bone marrow. All of these cells develop from a type of cell found in the bone marrow, called a "hematopoietic stem cell."
The body is able to direct hematopoietic stem cells to develop into the blood components needed at any given moment. This is a very active process, with the bone marrow producing millions of different cells every hour. Most of the stem cells stay in the marrow until they mature into the different blood cells, which are released into the blood stream where they perform specific functions such as carrying oxygen, providing protection from infection, and helping blood clot. Small numbers of stem cells, however, can be found in the circulating blood, which allows them to be collected under certain circumstances. Various strategies can be employed to increase the number of hematopoietic stem cells in the blood prior to collection. (See 'Peripheral blood' below.)
Hematopoietic cell transplantation — Some of the most effective treatments for cancer, such as chemotherapy and radiation, are toxic to the bone marrow. In general, the higher the dose, the more toxic the effects on the bone marrow.
In hematopoietic cell transplantation, you are given very high doses of chemotherapy or radiation therapy, which is intended to kill cancer cells that may be resistant to more standard doses of chemotherapy; unfortunately, this also destroys the normal cells in the bone marrow, including stem cells. After the treatment, you must have a healthy supply of stem cells reintroduced, or transplanted. The transplanted cells then reestablish the blood cell production process in the bone marrow. Reduced doses of radiation or chemotherapy that do not completely destroy the bone marrow may be used in some settings. (See 'Non-myeloablative transplant' below.)
The cells that will be transplanted can be taken from the bone marrow (called a bone marrow harvest), from the bloodstream (called a peripheral blood stem cell collection, which requires that you take medication to boost the number of hematopoietic stem cells in the blood), or occasionally from blood obtained from the umbilical cord after the birth of a normal newborn (which are stored in umbilical cord blood banks).
TYPES OF HEMATOPOIETIC CELL TRANSPLANTATION — There are two main types of hematopoietic cell transplantation: autologous and allogeneic.
Autologous transplant — In autologous transplantation, your own hematopoietic stem cells are removed before the high dose chemotherapy or radiation is given, and they are then frozen for storage and later use. After your chemotherapy or radiation is complete, the harvested cells are thawed and returned to you.
Allogeneic transplant — In allogeneic transplantation, the hematopoietic stem cells come from a donor, ideally a brother or sister with a similar genetic makeup. If you do not have a suitably matched sibling, an unrelated person with a similar genetic makeup may be used. Under some circumstances, a parent or child who is only half-matched can also be used; this is termed a haploidentical transplant. In other circumstances, umbilical cord blood may be used in an umbilical cord blood transplant.
Myeloablative transplant — A myeloablative transplant uses very high doses of chemotherapy or radiation prior to transplantation with autologous or allogeneic hematopoietic stem cells.
Non-myeloablative transplant — A non-myeloablative transplant or reduced intensity transplant, allows you to have less intensive chemotherapy before transplantation with allogeneic hematopoietic stem cells. This approach may be recommended for a variety of reasons including your age, type of disease, other medical issues, or prior therapies.
Which type of transplant is best? — Your physician will determine whether allogeneic or autologous transplantation is best, based on many factors, such as the underlying disease, your age, your overall health, and availability of a suitable donor. This is a complex decision that often also involves your viewpoints, because the different forms of transplantation carry different risks. As a general rule, autologous transplantation is associated with fewer serious side effects, since you are given cells from your own body. However, an autologous transplant may be less effective than an allogeneic transplant in treating certain kinds of cancer.
In an allogeneic transplant, the donor's immune system, which is generated from the transplanted hematopoietic stem cells, recognize your cells, including the tumor cells, as foreign and rejects them. This beneficial reaction is called the graft-versus-tumor effect. In many cancers, the immune response caused by the transplanted cells improves the overall effectiveness of the treatment. This immune response helps kill off any residual cancer cells remaining in your body.
A major concern is that you will have an immune response against normal tissues as well, called graft-versus-host disease. (See 'Graft-versus-host disease' below.)
In a non-myeloablative transplant, it is hoped that the graft-versus-tumor effect, rather than the high-dose chemotherapy, will help eradicate the cancer, although graft-versus-host disease is a concern (see 'Graft-versus-host disease' below).
CHOOSING A DONOR — There are many possible choices for an allogeneic hematopoietic stem cell donor. These are described below. (See "Donor selection for hematopoietic cell transplantation".)
Matched donor — To help minimize the problems that can be caused by the expected immune response, a donor who has similar genetic makeup to you is preferred. Your cells will seem "less foreign" to the transplanted donor cells. Siblings (ie, brothers and sisters who share the same parents as you) are typically the only members of your family who can be fully matched at the critical genes called the human leukocyte antigen or HLA genes. Each sibling has a one in four chance of sharing the same set of HLA genes with you; these characteristics are critical for your body to accept the graft. Parents, children, and relatives almost never carry identical sets of HLA genes since there are many different genes and they do not share the same parents.
In certain circumstances a "haploidentical" transplant, may be suggested which means that the donor is half matched who can be a parent, child, sibling, or cousin.
Matched unrelated donor — If no siblings are available, if testing the blood of the siblings does not reveal a match, or if sibling donors are not felt to be suitable, a matched unrelated donor may be used. The search for an appropriate donor can be accomplished using transplant registries throughout the world.
Mismatched related donor or umbilical cord blood donor — If no matched sibling donor is available, development of alternative donor sources can identify a suitable donor for almost all patients who are in need of transplantation.
Some patients are offered treatment with cells from a partially matched family member (called mismatched related donor); the hematopoietic stem cell product may be specially prepared to minimize the immune response in the patient. Other options include half-matched (haploidentical) transplantation from a parent or a child or use of umbilical cord blood, which is collected from a healthy newborn infant at the time of delivery.
PRE-HEMATOPOIETIC CELL TRANSPLANTATION PROCEDURES — Hematopoietic cell transplantation regimens vary from one patient to another, and depend upon the type of cancer, the treatment program used by the transplant center, the clinical trial protocol (if the patient is enrolled in a clinical trial), as well as other factors. The most common components of the hematopoietic cell transplantation procedure are outlined here. You should talk with your transplant team about specific details of their program. (See "Preparative regimens for hematopoietic cell transplantation".)
Health evaluation — Before undergoing hematopoietic cell transplantation, you will have a complete evaluation of your health. Your complete health history is reviewed by the transplant team. Most patients also have a number of tests.
Your mental health is reviewed because of the stress and demands of stem cell transplantation; some patients meet with a mental health counselor to discuss concerns and to plan coping strategies.
You will also meet with a transplant coordinator or nurse to discuss the transplant process. Because patients who receive donor bone marrow are hospitalized for several weeks to months, it is important that you have a clear understanding of what will happen and what services are available. Some patients prefer to have a friend or family member accompany them, tape record the conversation with the transplant physician, or have this information in writing so that they can review it later.
In many cases, patients undergo hematopoietic cell transplantation while they are in remission from their underlying disease. You may feel well going into treatment, but you should be prepared to feel poorly for a period of time. You must understand that you will require intensive treatment and monitoring, but that there are long-term benefits from the treatment.
Life planning — Patients who will be in the hospital for several weeks or months need to make plans regarding their family, home, finances, pets, and employment. The National Marrow Donor Program has excellent information about these and other stem cell transplantation related topics.
During the pre-transplant planning process, you should consider completing an advanced directive. This is a legal document that describes the type of care you want in case you are unable to communicate. Advance directives include a living will, durable power of attorney, and healthcare proxy; a social worker or attorney can provide guidance about what documents are needed. The laws surrounding these documents vary from one state to another, so it is important to be sure the correct guidelines are used.
Central line placement — A number of medications will be required before, during, and after hematopoietic cell transplantation. To avoid the need for multiple intravenous lines and needle sticks, most patients will have a central line placed before treatment begins. This requires a short surgical procedure to insert a thin, flexible plastic tube into a large vein in the chest, above the heart. The line usually has two or three ports, which can be used to infuse medications or blood products (including the hematopoietic stem cell product), as well as to withdraw blood samples.
After the central line is placed, you must keep the area clean and watch for signs and symptoms of infection (pain, redness, swelling, or fluid drainage from the site, fever or chills). You will be instructed on how to care for you central line. Most patients find this a great convenience since it avoids the need for other IVs and greatly reduces the number of needle sticks.
Harvesting hematopoietic stem cells — If you are having an autologous transplant, hematopoietic stem cells will be removed from your body before intensive chemotherapy or radiation begins. The most common sources for hematopoietic stem cells are bone marrow and blood.
Bone marrow — If your bone marrow has been invaded with cancer cells, hematopoietic stem cell removal may be preceded by one or more courses of chemotherapy. Removal (called harvest) of bone marrow stem cells is done while you are under general or epidural anesthesia. The harvest is done by using a long needle to repeatedly remove a sample of bone marrow fluid from multiple areas in your pelvic and hip bones.
Peripheral blood — The harvest of peripheral blood stem cells is similar to the process of platelet donation and is more frequently used than a bone marrow harvest for an autologous transplant. It uses an apparatus, called an apheresis device, which removes hematopoietic stem cells and other cells from blood by a filtration process. Blood is removed from a vein in one location, filtered, and then returned to a vein in another location. The process does not require anesthesia or hospitalization. The donor's hematopoietic stem cells quickly grow back following the harvest.
In order for there to be sufficient numbers of hematopoietic stem cells in the blood, you (or the donor) must first be treated with either chemotherapy or a growth factor that stimulates the production and release of hematopoietic stem cells into the blood. Healthy donors only receive growth factor; patients with cancer may receive growth factor alone or chemotherapy plus growth factor. The most commonly used growth factor is granulocyte colony-stimulating factor (G-CSF or Neupogen).
Allogeneic bone marrow harvest — People who donate their bone marrow will undergo harvest the day of transplant or one day prior. The donor is usually given general anesthesia to prevent pain.
Following the procedure, pain in the donor is usually relatively minor and can be treated with pain medications such as acetaminophen. The donor rarely requires hospitalization following the procedure, and generally returns to his or her prior state of health within one to two weeks.
Myeloablative therapy — As noted above, many patients receiving hematopoietic cell transplantation will undergo myeloablative therapy, which destroys bone marrow function as part of the intensive treatment for the patient's underlying cancer. The purpose of this treatment is to reduce the amount of cancer in the body and also to suppress the immune system adequately so that the graft will not be rejected. Depending upon the underlying disease and other factors, this phase of treatment may involve intensive chemotherapy, total body irradiation (radiation therapy), or both.
Preventing infection — When bone marrow function is destroyed, you are at risk for developing life-threatening infections because you have temporarily lost your ability to produce white blood cells (the infection-fighting cells in the blood). You are also at risk for excessive bleeding due to the reduced number of platelets in the blood. (See "Prevention of infections in hematopoietic cell transplant recipients".)
It is important to minimize your exposure to bacteria, viruses, and fungi after myeloablative therapy because even a small number of organisms (that are usually encountered every day) can cause serious infection.
Patients who undergo allogeneic transplant are often placed in protective isolation in a private room. The room's air is filtered and air from the room is forced out when the door is opened (called a positive-pressure room). This isolation, combined with feeling poorly, can be challenging to some people who may feel depressed and/or anxious. Discussing these issues with your health care team is very important.
Special precautions are required for all persons who enter the room to reduce the chance of infection. Hand washing is one of the most important precautions, and has been shown to significantly reduce the chance of transmitting infection. Visitors should NOT visit if they feel unwell and should NOT bring fresh fruit, plants, or flowers into your room because these can harbor potentially dangerous microorganisms.
Other measures may be taken to reduce the chance of infection. For example, antibiotics, antifungal, and/or antiviral medications may be given to prevent infections. Cleanliness is important and your transplant center will guide you in the things you can do to decrease the risks for infection.
Your diet may be restricted to exclude items that contain potentially infectious organisms. For example, all foods should be cooked until hot, raw fruits and vegetables should be avoided, and drinking water should be sterilized. Your transplant center will help you with your dietary choices during this time.
Different transplant centers use different precautions and your health care team will discuss the precautions and procedures that they expect.
Blood product transfusions — During the time that the marrow is not functioning, you will likely require transfusion of blood products, such as red cells, which carry oxygen to the tissues, or platelets, which help prevent bleeding. These blood products have no white blood cells and are irradiated to reduce the risk of an immune response.
HEMATOPOIETIC CELL TRANSPLANTATION PROCEDURE — When the intensive chemotherapy and/or radiation is complete, you will be given an infusion of the harvested bone marrow or peripheral blood stem cells. The infusion is given through an intravenous (IV) line, usually the central line. The infusion usually takes about an hour, and usually causes no pain. If you cannot receive blood products due to religious or other reasons this should be discussed with the transplant team prior to transplantation.
The hematopoietic stem cells find their way to the bone marrow, where they will reestablish normal production of blood cells; this process is called engraftment. Determining when engraftment has occurred is important because it is used to determine when it is safe for you to go home and/or reduce isolation procedures. Medications that stimulate the bone marrow to produce white and red cells may be used routinely or when engraftment is slower than expected. (See "Hematopoietic support after hematopoietic cell transplantation".)
Engraftment is measured by performing daily blood cell counts. Neutrophils are a type of white blood cell that are a marker of engraftment; the absolute neutrophil count (ANC) must be at least 500 for three days in a row to say that engraftment has occurred. This can occur as soon as 10 days after transplant, although 15 to 20 days is common for patients who are given bone marrow or peripheral blood cells especially if methotrexate is used to reduce the risk of graft-versus-host disease. Umbilical cord blood recipients usually require between 21 and 35 days for neutrophil engraftment.
Platelet counts are also used to determine when engraftment has occurred. The platelet count must be between 20,000 and 50,000 (without a recent platelet transfusion). This usually occurs at the same time or soon after neutrophil engraftment, but can take as long as eight weeks and even longer in some instances for people who are given umbilical cord blood.
HEMATOPOIETIC CELL TRANSPLANTATION SIDE EFFECTS — The high-dose chemotherapy and total body irradiation required for hematopoietic cell transplantation can have serious side effects. You should discuss the expected side effects, toxicities, and risks associated with hematopoietic cell transplant before deciding to undergo the procedure. You will be asked to sign a consent form indicating that you have received verbal and written information to understand the risks and benefits of the proposed treatment, possible treatment alternatives, and that all your questions have been answered.
Common side effects — Some of the most common side effects include:
●Mucositis (mouth sores), abdominal pain and diarrhea – Mucositis and diarrhea are caused by the damage done to rapidly dividing cells (such as skin cells in the mouth and digestive tract) by chemotherapy and radiation. If mucositis is severe and affects your ability to eat, intravenous nutrition (called TPN, total parenteral nutrition) may be given. Pain medications are usually given as well. You may also have pain in your chest and abdomen that will be addressed by your transplant team.
●Nausea and vomiting – Nausea and vomiting can be prevented and treated with a combination of medications. If you have important preferences that have helped you in the past, you should discuss these with your transplant team.
●Loss of hair – Loss of hair is common and temporary, and generally includes hair on the head, face, and body. After high-dose chemotherapy and radiation are completed, hair begins to regrow after two to three months. No treatment is available to prevent hair loss or speed its regrowth.
●Infertility – The risk of permanent infertility after stem cell transplant depends upon the treatments used (high-dose chemotherapy versus total body irradiation, ablative versus non-ablative regimen) and dosage given. If you are of reproductive age, you should speak with your healthcare provider about options for lowering the risks of infertility and the option of donating eggs or sperm before treatment begins. (See "Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery".)
●Organ toxicity – The lungs, liver, and bones are at greatest risk of damage as a result of treatments used with stem cell transplantation. People who have total body irradiation can develop cataracts in the eyes, although this complication is less common with current methods of delivering radiation treatment.
●Secondary cancers – There is a small risk of a second cancer developing in patients who undergo hematopoietic cell transplantation, probably as a result of the treatments used for the first cancer as well as the treatments required for transplant. The second cancer usually develops several years (typically three to five) after hematopoietic cell transplantation. (See "Secondary cancers after hematopoietic cell transplantation".)
Graft-versus-host disease — Between 10 and 50 percent of patients who receive an allogeneic transplant experience a side effect known as graft-versus-host disease (GVHD). Graft-versus-host disease is separated into acute and chronic phases due to timing and clinical presentation. This problem does not occur following autologous transplantation (when the patient is the donor). (See "Prevention of graft-versus-host disease".)
The "graft" refers to the transplanted hematopoietic stem cells; the "host" refers to the patient. Thus, graft-versus-host disease refers to a condition in which the donor's immune cells attack some of your organs. GVHD is the biggest single threat, other than the underlying disease, to the success of a hematopoietic cell transplant.
Treatments are given to help prevent GVHD, and generally include immunosuppressive medications, antibiotics, and sometimes steroids. If GVHD develops, additional treatment with high-dose steroids may lessen its severity. Symptoms can include skin rash, diarrhea, liver damage, or other problems, depending upon the organ that is affected. (See "Treatment of chronic graft-versus-host disease".)
Graft failure — Failure of engraftment is a rare complication that occurs in approximately one percent of cases following hematopoietic cell transplantation. The risk of graft failure can be higher depending upon the type of transplant and the source of hematopoietic stem cells. Discuss these risks with the transplant team prior to treatment. (See "Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation".)
Risk of death — Hematopoietic cell transplantation carries a risk of treatment-related death. The risk of death depends upon your age, the nature of the underlying disease, the type of transplant (autologous or allogeneic), and other factors, including the skill and expertise of the institution where treatment is offered. Your risk, as well as the potential benefits of hematopoietic cell transplantation, should be discussed with the treatment team before any decision is made about undergoing a transplant procedure.
POST-HEMATOPOIETIC CELL TRANSPLANTATION CARE — After engraftment occurs, blood cell counts continue to rise and the immune system becomes stronger. You will usually be cared for by the transplant team and monitored closely for complications.
Non-myeloablative transplants may be done on an outpatient basis, allowing you to sleep at home. Other types of transplantation require you to stay in the hospital for three to five weeks following transplantation. In all cases, frequent visits to the healthcare provider's office are needed following discharge. If you live a distance from your provider, you should arrange to live in a place within reasonable driving distance to the treatment center until at least 100 days have passed since the transplant.
Patients who undergo hematopoietic cell transplantation are at an increased risk of infection for many months following transplantation. You should be aware of these risks and monitor yourself for symptoms of infection, including fever (temperature greater than 100.4°F or 38°C), pain, or chills. You may be given antibiotics to prevent infections.
Studies have shown that most patients who undergo transplant and remain free of cancer have a good quality of life. Most patients are able to be active, employed, and in reasonably good health. Quality of life usually continues to improve in the months following transplant.
CLINICAL TRIALS — A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies, and patients who will undergo hematopoietic cell transplantation may be asked to participate. Ask a healthcare provider for more information about clinical trials, or read further at the following web sites.
Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).
DATA COLLECTION — Transplant centers are required to submit outcomes to the Center for International Bone Marrow Transplant Registry (CIBMTR). Only data related to your disease and treatment are collected and the data is only used to assess transplant outcomes.
●Hematopoietic cell transplantation (also called bone marrow transplantation or stem cell transplantation) is a treatment used in some types of cancer particularly malignancies of the blood.
●Bone marrow is the soft, spongy area in the center of some of the larger bones of the body. The marrow produces all of the different cells that make up the blood, such as red blood cells, white blood cells, and platelets. All of these cells develop from a type of basic cell found in the bone marrow, called a hematopoietic stem cell.
●In hematopoietic cell transplantation, the patient is given very high doses of chemotherapy or radiation therapy, which kills cancer cells and destroys all the normal cells developing in the bone marrow, including the critical hematopoietic stem cells. After the treatment, the patient must have a healthy supply of hematopoietic stem cells reintroduced, or transplanted.
●There are two types of hematopoietic cell transplantation, autologous and allogeneic. An autologous hematopoietic cell transplant uses a patient's own bone marrow or blood. An allogeneic hematopoietic cell transplant uses a donor's bone marrow or blood. The donor is usually a relative of the patient, although unrelated donors or umbilical cord blood are sometimes used.
●Most patients who have hematopoietic cell transplantation must remain in the hospital for several days or weeks during their treatment and recovery. It is important to understand and follow the hospital's hematopoietic cell transplantation treatment plan to minimize the risk of complications and to know what to expect in advance.
●The treatments required before and during hematopoietic cell transplantation can have serious side effects. Patients should be aware of the most common side effects (eg, diarrhea, nausea, vomiting, mouth sores) as well as the types of treatments that are available to improve comfort.
●Following hematopoietic cell transplantation, most people stay in the hospital for several weeks. However, even after going home, frequent visits with a doctor or nurse are needed for three to six months.
●Clinical trials are carefully controlled studies of new treatments or new combinations of current treatment. Clinical trials help researchers to learn the best way to treat specific conditions. Some patients who undergo hematopoietic cell transplantation will be asked to participate in a clinical trial.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our website (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Patient education: Autologous bone marrow transplant (The Basics)
Patient education: Allogeneic bone marrow transplant (The Basics)
Patient education: Donating bone marrow or blood stem cells (The Basics)
Patient education: Leukemia in adults (The Basics)
Patient education: Leukemia in children (The Basics)
Patient education: Lymphoma (The Basics)
Patient education: Acute lymphoblastic leukemia (ALL) (The Basics)
Patient education: Acute myeloid leukemia (AML) (The Basics)
Patient education: Chronic lymphocytic leukemia (CLL) (The Basics)
Patient education: Chronic myeloid leukemia (CML) (The Basics)
Patient education: Diffuse large B cell lymphoma (The Basics)
Patient education: Follicular lymphoma (The Basics)
Patient education: Hodgkin lymphoma in adults (The Basics)
Patient education: Hodgkin lymphoma in children (The Basics)
Patient education: Myelodysplastic syndromes (MDS) (The Basics)
Patient education: Sickle cell disease (The Basics)
Patient education: Immune thrombocytopenia (ITP) (The Basics)
Patient education: Beta thalassemia (The Basics)
Patient education: Chronic granulomatous disease (The Basics)
Patient education: Invasive aspergillosis (The Basics)
Patient education: When your child has sickle cell disease (The Basics)
Patient education: Neutropenia and fever in people being treated for cancer (The Basics)
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
This topic currently has no corresponding Beyond the Basics content.
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Donor selection for hematopoietic cell transplantation
Hematopoietic support after hematopoietic cell transplantation
Immunotherapy for the prevention and treatment of relapse following allogeneic hematopoietic cell transplantation
Preparative regimens for hematopoietic cell transplantation
Prevention of graft-versus-host disease
Hematopoietic cell transplantation (HCT): Sources of hematopoietic stem/progenitor cells
Treatment of chronic graft-versus-host disease
Prevention of infections in hematopoietic cell transplant recipients
Fertility and reproductive hormone preservation: Overview of care prior to gonadotoxic therapy or surgery
Secondary cancers after hematopoietic cell transplantation
The following organizations also provide reliable health information.
●National Library of Medicine
●National Marrow Donor Program
●National Cancer Institute
●American Cancer Society
●The Leukemia & Lymphoma Society
●The American Society of Clinical Oncology
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