Bone Marrow Transplantation for Non-Hodgkin's Lymphoma

If you have non-Hodgkin's lymphoma, or NHL, then you have one of the three different subgroups: either low grade, intermediate grade, or high grade. I will discuss the use of bone marrow transplantation for each grade of NHL, but let us first examine the different ways bone marrow can be transplanted.
Types of Bone Marrow Transplantation

There are three types of bone marrow transplantation: autologous, allogeneic, and syngeneic.

Autologous Bone Marrow Transplantation
With autologous bone marrow transplants, a portion of your own bone marrow cells are removed and stored in a freezer before you receive chemotherapy, or chemotherapy and radiation therapy together (chemoradiotherapy), in powerful doses so that as many cancer cells can be killed as possible. Then your bone marrow cells that were stored in the freezer—and which were saved from the toxic effects of your therapy—are put back in your body. The benefit of this type of bone marrow transplantation is that higher doses of chemotherapy can be given to knock out the cancer without fear of harming the bone marrow.


Allogeneic Bone Marrow Transplantation
An allogeneic bone marrow transplant uses bone marrow cells from another person (donor). The donor could be a family member (usually a sibling) or be unrelated. Bone marrow cells from unrelated donors come through programs such as the National Marrow Donor Program or one of the Umbilical Cord Blood banks recently established around the country.

There are three benefits of allogeneic bone marrow transplantation. The first is similar to that with autologous bone marrow transplantation: the ability to administer very high doses of chemotherapy and radiotherapy to hit the cancer the hardest. The second benefit is the possibility of a "graft versus tumor effect." (Physicians refer to transplanted organs or bone marrow as grafts.) When an allogeneic transplant is performed successfully, the recipient in effect receives a new immune system (from the donor's cells). The new immune system can then attack the cancer in the recipient. This effect is particularly powerful in leukemias, and its importance in NHL is being actively studied. A serious side effect of an allogeneic transplant may occur if this new immune system reacts against your normal cells in what is called "graft-versus-host disease." However, when this occurs along with a graft-versus-tumor effect, the benefit to you may outweigh any unwanted side effects.

A third benefit of this type of bone marrow transplant is of particular importance in diseases in which there may be cancer cells in your bone marrow (which can happen with NHL) because with allogeneic transplantation you receive "new" healthy bone marrow.

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Cutting Edge Therapy: Monoclonal Antibody Treatment for Non-Hodgkin's Lymphoma

Chemotherapy and radiation therapy have been effective treatments for patients with non-Hodgkin’s lymphoma, or NHL. Patients with NHL usually respond well to either treatment, and some can be cured. However, for many patients, these treatments are not that effective and can be very toxic. Because of these limitations, intensive efforts have been made to develop new therapies to fight NHL.
"Monoclonal-antibody–based" therapy is a new development in NHL therapy and has been demonstrated to be safe and effective for certain types of patients. One drug rituximab (also known as Rituxan®) has been approved by the FDA for treatment of NHL. (I will discuss it in detail later in this article). Other monoclonal antibody treatments, such as Bexxar®, are being studied and may soon be available as well. All offer great promise in further improving the effectiveness and tolerability of the current treatment for NHL. (rituxumab, Bexxar, and other similar treatments will be discussed later in the article.)

What Are Monoclonal Antibodies?

Antibodies are substances made by our own immune system to fight against various foreign substances. Our bloodstream contains many different types. Each antibody has a specific target (antigen) that it looks for and binds to, like a key, which fits only into one lock. When an antibody binds to its antigen target, the antibody alerts the immune system to respond against the foreign substance. This is an important part of our body’s defense against infection.


A monoclonal antibody is one that is generated in a laboratory, not in our body, to be directed against one single target. Rather than a diverse group of antibodies like those found in our bodies, monoclonal antibodies are made to be all exactly the same. The reason why they were developed was to allow a treatment to be directed to one specific target. Monoclonal antibodies developed to treat cancers are made to be directed against a single target on a tumor to cause anti-tumor effects.

Different antibodies have been engineered and developed through different processes. For several reasons, most antibodies are initially created as murine (or mouse) type. This does not mean that they are made in an animal but simply that the antibody structure is from a mouse antibody. Antibodies can be chimeric (half mouse, half human) or humanized (mostly human). All types have been evaluated, yet the potential differences in efficacy or toxicity have not definitively been established.

How Do Monoclonal Antibody Treatments Work in Lymphoma?

Most non-Hodgkin’s lymphoma patients (about 90%) have tumors that are made up of B cells (B lymphocytes), a type of white blood cell. Since most NHL patients have these similar B cells, treatment using a monoclonal antibody directed against these tumor B cells has great potential to be effective in different patients. Several different monoclonal antibodies have been evaluated as potential treatments for lymphoma.
As treatment for NHL, monoclonal antibodies have been tested either alone ("naked" antibodies) or have been joined with a toxin which can kill cells, in order to target this toxin directly towards tumor cells. Radioactive particles have also been attached to monoclonal antibodies (radiolabeled antibodies) to make radiation therapy more effective. Patients who have low blood counts or have a lot of tumor cells in their bone marrow may not be candidates for treatment with radiolabeled antibodies because the radiation may destroy too many of their red and white blood cells (a side effect called hematologic toxicity). The differences in monoclonal antibody structure and targets, whether or not they are linked to radioactive particles or toxins, as well as the differences in patients, play an important role in the choice of treatment and how effective and safe a particular type of monoclonal antibody will be.

What Monoclonal Antibody Treatments Are Available for NHL?

Rituximab (Rituxan®)
Rituxan is the only monoclonal antibody treatment currently approved for NHL. Rituxan is a chimeric antibody that binds to a specific antigen target present on the surface of B cells (again -- this is the cancer cell type in most NHL patients). If Rituxan is given as a course of treatment without anything else, it is usually given once a week for 4 weeks. People receive it as outpatients, but it is given intravenously, over a period of several hours. Most of the common side effects are fever, chills, rigors or shakes, and are most likely to occur during the first treatment. In contrast to many chemotherapy agents, Rituxan does not have other significant side effects like nausea, vomiting, hair loss, and low blood counts. Rituxan has been most extensively studied in patients that have relapsed low grade NHL: about 50% of the patients respond with about 5% having a complete remission. Rituximab has also been combined with a radioactive particle to enhance its effect with directed radiation therapy, as mentioned above. This treatment (called Y2B8 or Zevalin) is given twice intravenously in an outpatient clinic, with a week between doses. During the week between doses, nuclear medicine scans are used to determine the dosing in the second treatment. In the initial studies the anti-tumor effects and response rates are significantly higher using this radiolabeled combination, and the toxic side effects like low blood counts appear to be manageable.

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Immunohistochemistry is a diagnostic test

Immunohistochemistry is a diagnostic test. It uses antibodies previously marked with a substance that can be seen under the microscope. The antibodies are specific to an antigen that the test is able to detect. These antibodies have high affinity to their antigens so the test has high specificity, not necessarily high sensitivity which depends on other factors.

It is widely used to detect and classify cancer cells Antibodies can be polyclonal or monoclonal. How can this test affect treatment options for a given disease? I will explain this through an example:

Cells, cancer or not, have, different antigens (markers) on their membranes, such as receptors, glycoproteins, etc. This markers define populations of cells like CD4 and CD8 T-lymphocytes and B-lymphocytes (CD-20 + or -). This markers, when they are unique to a specific type of cell, can help not only to differentiate them, but also to target them with specific antibodies. These antibodies can be used for tests and also as treatments.

I will explain this through an example:

A patient comes to the office with a biopsy of his pleura, and it reports "Diffuse large B-cell lymphoma". The immunoperoxidase shows CD20 (+) (a B cell marker) and Bcl-6 (a marker of its origin from the germinal center).

If this patient didn't have a CD20 (+) report then he wouldn't be eligible for Rituximab therapy and the prognosis would be far more somber.

Rituximab is a genetically engineered chimeric murine/human monoclonal antibody that targets CD20 receptors that are present in certain B-cell non-Hodgkin lymphomas. Once it reaches its intended target, it activates other immune cells and the complement system to destroy the b-cell. It is part of the new therapies that are being used in Hemato-oncology.

Before Rituximab, the standard therapy for B-cell lymphoma was CHOP therapy. This therapy had a success rate of 40% to 50%. (3-year event-free rate)

When Rituximab is used in conjunction with CHOP chemotherapy, it has shown a success rate of up to 99% (when used in early stages).

Now you see the difference.

However this new therapies are not exempt of potentially hazardous effects, and this page is not intended as an advertisement of Rituximab, but to show an example of the application of antibodies in different settings (diagnostic and therapeutic.

Francisco Santander M.D. Visit the source Immunohistochemistry and new lymphoma treatments

Lymphoma

Summary
Lymphoma is cancer of the lymphoid tissue, which is part of the lymphatic system. A major component of the immune system, the lymphatic system consists of organs, lymph nodes and lymphatic vessels. This system manufactures lymphocytes and transports lymph (fluid made of plasma and white blood cells) from tissues to the bloodstream. Although other forms of cancer may spread to parts of the lymphatic system, lymphoma is the only form that originates in the system.

Lymphoid tissue is formed by various types of immune cells that work together to resist some types of infection and other threats, such as cancer. Lymphocytes are the main type of cell found in the lymphoid tissue. In lymphoma, abnormal lymphocytes continually grow for no reason. This results in abnormal enlargement of the lymph nodes and other body organs containing lymphocytes, causing lumps to develop in the body.

Lymphomas can be categorized into two main groups. One group, characterized by the presence of specific cells (called Reed-Sternberg cells), is known as Hodgkin’s lymphoma or Hodgkin’s disease. All other forms of lymphomas are known as non-Hodgkin’s lymphoma. Cases of non-Hodgkin’s lymphoma are far more common.


Most lymphomas develop as a result of noninherited mutations in the genes of growing lymphocytes. According to the National Cancer Institute (NCI), lymphomas account for about 5 percent of all cases of cancer in the United States. They can occur in both children and adults.