When most people think about bone marrow transplants they envision two parties: the patient who is suffering from a bone marrow disorder such as leukemia, and a bone marrow donor whose healthy bone marrow is used to replace the patient's diseased marrow during transplant. This two-party transplant is called an allogeneic BMT, or syngeneic BMT if the donor is an identical twin.
However another type of BMT, called an autologous (pronounced au-tol'-o-gous) BMT is actually much more common. In an autologous BMT the patient is both the donor and the recipient of the bone marrow. Some 5,000 autologous BMTs are performed each year, outpacing allogeneic and syngeneic BMTs two to one.
Some complications associated with allogeneic BMTs such as graft-versus-host disease are avoided with autologous BMTs. The risk of infection is also somewhat less in autologous BMTs because the large doses of immunosuppressive medications given to patients in allogeneic BMTs to prevent GVHD are not needed.
Autologous BMTs (ABMTs) have expanded treatment options for thousands of patients diagnosed with life-threatening diseases such as Hodgkin's disease and non-Hodgkin's lymphoma, breast cancer, ovarian cancer, testicular cancer and pediatric solid tumors such as neuroblastoma. The autologous BMT has also given new hope to hundreds of patients suffering from leukemia who were previously denied a BMT because a suitable bone marrow donor could not be found.
Not all patients diagnosed with these diseases are candidates for an autologous BMT. The type of disease, the stage to which it has progressed, the responsiveness of the disease to prior treatment, and the patient's age and general physical condition are all factors that will determine whether a patient is considered a suitable candidate for an autologous BMT.
With the exception of leukemia, diseases treated by autologous BMTs are usually not disorders that start in or involve the bone marrow. Rather, they're "malignant" or cancerous tumors located elsewhere in the body that are responsive to treatment with high-dose chemotherapy and/or radiation. The high doses of chemotherapy and/or radiation, however, also destroy the patient's bone marrow. Without bone marrow, the body is unable to manufacture blood cells needed to defend against infection, carry oxygen and prevent bleeding. An autologous BMT enables physicians to "rescue" the patient from the effects of high-dose chemotherapy and/or radiation treatment by replacing the destroyed bone marrow.
For each disease discussed below, long-term survival rates following treatment with an autologous BMT are cited. Keep in mind that these numbers are only ballpark estimates which cover a wide range of circumstances. The projected survival rate of an individual patient will depend on his or her age and general physical condition, the specific characteristics of the disease, the stage to which the disease has progressed, and the responsiveness of the disease to prior treatment. The patient's own physician can provide the best assessment of a patient's chances for long-term survival following an autologous BMT.
Autologous BMTs are most frequently used to treat patients diag nosed with Hodgkin's disease and non-Hodgkin's lymphoma. In Hodgkin's disease, an abnormal cell called the Reed-Sternberg cell may be present in one or more Iymph nodes. Without treatment, this defective cell infiltrates neighboring organs and tissues, disrupting normal functions.
Similarly, in non-Hodgkin's lymphomas, defective Iymphocytes (a type of white blood cell) are produced in the lymph nodes, bone marrow, spleen and/or gastrointestinal tract. Left unchecked, they invade other tissues and organs, interfering with their normal functions.
Patients with Hodgkin's disease and non-Hodgkin's lymphoma can often be cured by radiation and/or chemotherapy. However, if patients have not achieved a remission with radiation /chemotherapy, have relapsed after chemotherapy, or have experienced progression of the disease while undergoing chemotherapy, an autologous BMT may be the best option to save their life. Patients with non-Hodgkin's lymphoma whose tumors are not responsive to chemotherapy (ie. the size of the tumor has not shrunk after chemotherapy) are less likely to achieve a long-term cure with an autologous BMT than those whose tumors are responsive to chemotherapy. This is not true for patients with Hodgkin's disease.
Patients with advanced Hodgkin's or non-Hodgkin's lymphoma who undergo an autologous BMT have a 25 to 50 percent chance of long term survival. Without a BMT, their chances for long term survival are 5 to 10 percent.
Treatment of leukemia with an autologous BMT is becoming more common. Patients with acute lymphocytic leukemia (ALL) or acute myelogenous leukemia (AML) (also called acute non-lymphocytic leukemia or ANLL) may be candidates for an autologous BMT if their disease is in complete remission. Since a complete remission is rarely achieved in patients with chronic myelogenous leukemia (CML), an autologous BMT is usually not a treatment option for these patients (although some very interesting studies are now underway using ABMTs to treat this disease).
Leukemia is a disease of the bone marrow, the organ that produces the body's blood cells. In patients with leukemia, a large number of abnormal white blood cells are produced in the bone marrow and interfere with the production of normal blood cells. Without normal blood cells, the body's ability to fight infection, carry oxygen to tissues, and prevent bleeding is impaired. Patients with acute leukemia will die within a matter of weeks or months without treatment.
Patients with acute myelogenous leukemia (AML or ANLL) who've achieved a first complete remission with standard chemotherapy may be able to increase their chances for long-term survival significantly with a BMT. Without a BMT, their expected long-term survival rate is 20 to 30 percent.
Researchers are currently studying whether autologous BMTs are more effective than standard chemotherapy in treating patients with AML in first remission. Preliminary results suggest that survival rates do improve with an autologous BMT, but further study is underway to determine whether these improved survival rates are the result of the autologous BMT or other factors such as the type of patients chosen to participate in the study or the sub-type of AML affecting the patient.
BMTs are also performed on patients with acute lymphocytic leukemia. ALL typically strikes children. Because the cure rate with standard chemotherapy is quite high, only a few studies have been conducted to date on the use of BMTs in the treatment of ALL. While the studies have found that both autologous and allogeneic BMTs are an effective treatment option for ALL patients, some experts believe that too little data are currently available to reliably project long-term survival rates.
People are often surprised that an autologous BMT is a treatment option for patients with leukemia. Since it's known that malignant cells may remain in the bone marrow of patients with leukemia even after a complete remission has been achieved, they question why it makes sense to harvest imperfect marrow and re-infuse it back into the patient via an autologous BMT.
Researchers are not sure of the answer, but some theorize that the number of malignant cells re-introduced into the patient is so small that the body's normal defenses can destroy them before they proliferate. Many centers purge the harvested bone marrow to reduce the number of cancerous cells that remain in the sample. For more information on purging see page 30.
Breast cancer is the third most common cancer in women, resulting in thousands of deaths annually. In 1990, 150,000 new cases were diagnosed and 44,000 deaths from breast cancer were reported.
The initial treatment for breast cancer is surgery with or without radiation. In cases where the risk of relapse is high, chemotherapy has sometimes been administered after surgery. However, once breast cancer has spread or become metastatic (Stage IV) it is no longer curable with conventional treatment.
Over the past five years, researchers have been studying the possibility of treating advanced stage breast cancer with a combination of highdose chemotherapy and an autologous BMT. Since an autologous BMT enables a physician to replace the patient's bone marrow after the chemotherapy treatment, higher doses of chemotherapy can be used than previously possible.
The results of early clinical studies in which high-dose chemotherapy and an autologous BMT were administered to Stage IV breast cancer patients who had previously undergone intensive chemotherapy treatment were encouraging. A remission was achieved in 27 percent of the patients. That remission, however, was of short duration.
Subsequent studies conducted with patients who had just become Stage IV, had not previously undergone intensive chemotherapy treatment or were in their first relapse after remission, found that administering a cycle of chemotherapy before the high- dose chemotherapy and an autologous BMT produced remissions in 50 percent or more of the cases, with some remissions lasting three years or more.
Studies are now underway to determine whether chemotherapy followed by high-dose chemotherapy and an autologous BMT will improve the survival rates of some Stage II breast cancer patients (in whom the disease has spread to lymph nodes under the arm) and some Stage III patients who are in a first remission and have not yet relapsed, but are in a high risk category for relapse a.e. the disease has spread to 10 or more lymph nodes). Early results from the studies are encouraging.
Childhood neuroblastoma is a cancer affecting the nerves that run from the neck down the inside of the back to the pelvis. It occurs almost exclusivly in very young children. Radiation and surgery are used to treat the disease in early stages when it's localized, but chemotherapy has so far not cured more than a very small percentage of patients when the disease is widespread at diagnosis.
Researchers have attempted to increase the cure rate with high-dose chemotherapy and an autologous BMT. Studies have found that for patients in first remission whose tumor has become resistant to standard chemotherapy, 40 50 percent can achieve a remission lasting two years or more with high-dose chemotherapy and/or total body irradiation and an autologous BMT. Survival rates are not as favorable for patients undergoing an autologous BMT after a relapse. Long-term survival rates for patients treated with an autologous BMT are similar to results achieved with an allogeneic BMT.
Ovarian cancer, brain tumors, Ewing's Sarcoma, testicular cancer, and other solid tumor cancers may also be treated with autologous BMTs. Ask your doctor for information about the effectiveness of treating these diseases with an autologous BMT.
Purging is a technique used at some transplant centers to reduce the +number of cancerous cells that may be in bone marrow harvested from certain patients undergoing an autologous BMT. The theory behind purging is simple: by reducing the number of cancerous cells in the harvested bone marrow, the likelihood of relapse after an autologous BMT will be reduced.
Two different purging techniques are used. The first involves "monoclonal antibodies"-special proteins that distinguish malignant cells from normal cells and attach to the surface of the malignant cell. These "marked" malignant cells are then broken apart with additional proteins called "complement" or "immunotoxins". Alternatively, small magnetic beads or "microspheres" are coated with the monoclonal antibodies and mixed with the bone marrow. The marrow is then passedover electromagnets which remove the microspheres and malignant cells to which they've become attached.
A second technique is chemical or pharmacological purging. The bone marrow is incubated with chemicals more toxic to cancerous cells than normal cells. The marrow is then transplanted into the patient.
Most U.S. transplant centers now purge bone marrow harvested from patients with leukemia before an autologous transplant. Tests on animals have shown purging to be effective in removing leukemic cells that linger in the marrow. Recent European studies suggest a link between purging and improved long-term survival rates in this patient population.
Purging bone marrow harvested from patients with non- Hodgkin'slymphomas is more controversial. No studies to date have conclusively demonstrated that purging bone marrow improves the long-term survival for this group of patients.
Purging is generally not done on bone marrow harvested from patients with Hodgkin's disease. It's commonly done, however, on the bone marrow of patients with neuroblastoma.
Purging has its drawbacks. Pharmacological purging can damage normal as well as malignant cells, causing delayed engraftment of
platelets and granulocytes and extending the period in the hospital during which patients are susceptible to infection and bleeding. Problems associated with pharmacological purging are diminishing as researchers learn the optimal level of chemicals to use in the purging procedure.
The prognosis for long-term survival varies according to the disease being treated, the stage of the disease at which an autologous BMT was performed, the patient's age, prior treatment history, and any complications that may have developed during transplant. There is no guarantee that an autologous BMT (or any BMT for that matter) will cure the disease.
Nonetheless, the alternative is usually near-certain death. Each added day of life, therefore, is special. Most patients agree that the potential rewards of an autologous BMT are well worth the effort.
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