General Info on Blood related Cancers

LYMPHOMA is a general term for a group of cancers that originates in the lymphatic system. Lymphoma results when a lymphocyte (a type of white blood cell) undergoes a malignant change and begins to multiply, eventually crowding out healthy cells and creating tumors that enlarge the lymph nodes or other sites in the body. 56% of all the blood cancers diagnosed are lymphomas.

HODGKIN LYMPHOMA is a specialized form of lymphoma. It has characteristics that distinguish it from all other cancers of the lymphatic system, including the presence of an abnormal cell called the Reed-Sternberg cell. The incidence is higher in adolescents and young adults, and the cure rate is more than 84%, making it one of the most curable forms of cancer.

NON-HODGKIN LYMPHOMA represents a diverse group of cancers with the distinctions between types based on the characteristics of the cancerous cells. The groups are often classified as indolent or aggressive or low, intermediate and high grade. Non-Hodgkin lymphoma is a group of diseases and not just one type. Each histologic grouping is diagnosed and treated differently, and each has prognostic factors that categorize it as more or less favorable. The incidence of non-Hodgkin lymphomas increases with age. About 2.3 cases per 100,000 people occur in 20-24 year old individuals. The rate increases more than 19 times to 43.8 cases per 100,000 by age 60, and more than 40-fold to more than 100 cases per 100,000 persons after age 75.

In the Spring 2006 "Mayo Magazine", there is an article about a new MULTIPLE MYELOMA genomic research team. I found it very interesting, and thought I would share some of its contents with you.

"Mayo Clinic has earned its long-standing reputation as one of the best medical centers in the world for research and treatment of myeloma, and the staff of Mayo Clinic Cancer Center believes there has never been a better time for more optimism in the fight against this disease. But make no mistake, it is a fight. With striking advances in medical science comes the critical need for research programs to be organized, integrated and well -supported.

The new Mayo Clinic Multiple Myeloma Team, set in Arizona, is a shining example of such a program. It builds on the already recognized international reputation of the Mayo Clinic Myeloma Program, established in Rochester, Minnesota nearly a half century ago."

The article goes on to say that three internationally recognized research specialists who are pioneers in the genetics of myeloma will be joining the team. Their aim is to understand the nature of tumor cells, the significance of these abnormalities and how to best use this knowledge to generate targeted therapy.

According to the article, multiple myeloma is the second most common blood cancer, with 15,000 new cases diagnosed every year. It is a cancer of the plasma cells, which are found inside the bone marrow. Abnormal plasma cells multiply in a cancerous manner, causing anemia, bone destruction and reduced production of blood.

Hope you found this information to be helpful in learning more about the blood-related cancers. ...

Addition of Rituxan to Fludara May Improve Survival in Chronic Lymphocytic Leukemia

According to results recently presented at the 45th annual meeting of the American Society of Hematology (ASH), the addition of Rituxan® to Fludara® may improve survival as initial therapy for chronic lymphocytic leukemia (CLL). However, this was not a clinical trial directly comparing regimens, and further research is necessary to compare sequential therapy with Rituxan and Fludara to the combination of Rituxan and Fludara in order to establish clinical effectiveness of this combination as initial treatment of CLL.

CLL is a cancer involving the lymph (immune) system, which includes lymph nodes, blood and blood vessels found throughout the body, as well as the spleen, thymus and tonsils. This cancer is found in high quantities throughout circulating blood and in bone marrow (spongy material inside large bones that produces blood forming cells). CLL is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells, of which there are two types: B and T-cells.

These cells are produced in the bone marrow and each has a very specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal, accumulating in the blood, bone marrow, lymph nodes and spleen. This results in overcrowding of these areas, suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the ability of the body to fight infection. CLL is considered a slow-growing or low-grade cancer. Treatment for CLL may include chemotherapy, radiation therapy, biological therapy and/or stem cell transplantation.

The chemotherapy agent Fludara used alone is a standard treatment option for CLL, and results have indicated that Rituxan has anti-cancer activity in the treatment of CLL. In addition, research has demonstrated that the combination of Fludara and Rituxan is active in the treatment of CLL.

Rituxan is a monoclonal antibody that is produced through laboratory processes to bind to a portion (CD20) of B-cells, the most common cancerous type of cells in CLL. The binding action stimulates the immune system to attack the cell to which Rituxan is bound. Rituxan is approved by the U.S. Food and Drug Administration for the treatment of relapsed or refractory low-grade or follicular, CD20+, B-cell non-Hodgkin lymphoma. Researchers have been evaluating Rituxan alone and in combination with other therapies for the treatment of CLL.

Recently, researchers associated with the Cancer and Leukemia Group B (CALGB) analyzed data from two different studies. One study included 104 patients who were treated with the combination of Fludara and Rituxan for the treatment of CLL, and the second study included 179 patients who were treated with Fludara alone. Patients in the two trials had similar disease characteristics, and eligibility criteria for the two trials were virtually identical.

Two years following therapy, patients in the trial involving treatment with Rituxan plus Fludara had progression-free and overall survival rates of 67 percent and 93 percent, respectively. Patients in the trial involving treatment with Fludara alone had progression-free and overall survival rates of 45 percent and 81 percent, respectively, at two years following therapy. Researchers could not find any clinical variables besides treatment regimens that may have altered treatment outcomes between the two groups of patients.

The researchers concluded that the addition of Rituxan to Fludara appears to improve survival when used as initial therapy for CLL. However, further trials are necessary to compare the combination of Fludara plus Rituxan as initial therapy to sequential administration of Fludara and Rituxan (meaning a patient is treated with one agent after a recurrence following the initial agent) to truly determine the clinical benefit of Fludara plus Rituxan.

Patients with CLL may wish to discuss the risks and benefits of treatment with Fludara and Rituxan or the participation in a clinical trial evaluating different scheduling of Fludara/Rituxan or other promising therapeutic approaches.

Bexxar Effective in Advanced Follicular Non-Hodgkin Lymphoma

According to results recently presented at the 45th annual meeting of the American Society of Hematology (ASH), Bexxar® (tositumomab and Iodine I 131 tositumomab) produces long-term anti-cancer responses in patients with advanced follicular non-Hodgkin lymphoma.

Follicular lymphoma is a type of non-Hodgkin lymphoma (NHL), which is a form of cancer that begins in the cells of the lymph system. The lymph system includes the spleen, thymus, tonsils, bone marrow, lymph nodes and circulating immune cells. The main cells in the lymph system are lymphocytes, of which there are two types: B and T-cells. Each of these cells has a very specific function in aiding the body to fight infection. NHL is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells.

While NHL is categorized by the type of lymphocyte it involves, it is also further defined by the rate at which the cancer grows, based on the appearance of the cells under a microscope. Follicular lymphoma is a low-grade or indolent lymphoma that is slow growing.

Due to the side effects associated with chemotherapy and radiation, researchers have been investigating novel therapeutic strategies including radioimmunotherapy. Radioimmunotherapy involves treatment with a radioactive substance that is linked to an antibody that will attach to cancer cells when injected into the body. By delivering the radiation directly to the cancer, more normal tissue is spared from radiation and there are fewer side effects.

Bexxar is a new radioimmunotherapeutic agent that has recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with CD20-positive, follicular NHL, whose disease has stopped responding to Rituxan® or has recurred following chemotherapy. Bexxar is an antibody with radioactive iodine 131 attached. The monoclonal antibody portion of the drug attaches to a protein (CD20) found only on the surface of B-lymphocytes, such as cancerous B-cells found in many forms of NHL. The radioactivity that is spontaneously emitted targets the B-cell and destroys it.

The results presented at the 2003 ASH meeting included five studies evaluating Bexxar in the treatment of advanced follicular lymphoma. The entire patient population included 250 patients who had received several prior therapies. Some patients had stopped responding to the monoclonal antibody agent Rituxan, and some patients had never received Rituxan. The overall anti-cancer response rate following treatment with Bexxar was 56 percent, with a complete disappearance of detectable cancer occurring in 30 percent of patients.

Progression-free survival for at least one year (durable complete response) occurred in 28 percent of patients who had stopped responding to Rituxan, and 23 percent of patients who had never been treated with Rituxan. With an average follow-up of approximately 4.6 years, 75 percent of patients who achieved a durable complete response remained free of detectable cancer. Among patients who had never been treated with Rituxan, the average duration of anti-cancer response was nearly five years. Among patients who experienced a cancer recurrence following Rituxan, the average duration of anti-cancer response had not been reached at nearly four years.

The researchers concluded that Bexxar appears to provide high rates of durable complete responses in patients with follicular lymphoma who had received previous therapy. In addition, previous treatment with Rituxan did not appear to affect the effectiveness of Bexxar in the treatment of follicular lymphoma. Patients who had recurrent follicular lymphoma may wish to speak with their physician about the risks and benefits of treatment with Bexxar.

Two Autologous Stem Cell Transplants Improve Survival Over Single Transplant in Multiple Myeloma

According to results recently published in The New England Journal of Medicine, two autologous stem cell transplants appear to improve long-term survival over a single autologous stem cell transplant in patients with untreated multiple myeloma under the age of 65.

Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection.

In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone. Standard treatment for multiple myeloma is chemotherapy with or without stem cell transplant.

High-dose therapy (chemotherapy and/or radiation) kills more cancer cells than moderate doses. However, more healthy cells, including stem cells, are also killed due to the high doses, often causing significant side effects. Stem cells are immature blood cells produced in the bone marrow that mature into red blood cells, which carry oxygen to tissues; white blood cells, which fight infection; and platelets, which aid the blood in clotting.

Autologous stem cell transplants involve the collection of patient's stem cells prior to treatment and re-infusion following high-dose therapy to restore depleted blood cell levels. The high doses of therapy are often difficult for patients to tolerate, particularly the elderly. Thus, physicians often reserve high-dose therapy and stem cell transplantation for patients under the age of 65 years. Prior to high-dose therapy, patients are treated with moderate doses of chemotherapy, called "induction therapy".

Although some clinical results have indicated that two autologous stem cell transplants appear to improve survival over a single autologous stem cell transplant in patients with multiple myeloma, the first clinical trial directly comparing these two treatment strategies has only recently been conducted. This trial was conducted by a French consortium of 36 medical centers and involved 339 patients with newly diagnosed multiple myeloma who received either a single autologous transplant or a double autologous stem cell transplant. The single transplant patients were treated with high-dose melphalan and total body irradiation followed by stem cell transplantation. The double transplant patients were treated with high-dose melphalan and autologous stem cells followed by high-dose melphalan and total body irradiation and an additional autologous stem cell infusion. The induction therapy for all patients was a chemotherapy regimen referred to as VAD (vincristine, Adriamycin® and dexamethasone).

Seven years following therapy, progression-free survival was 21 percent following double stem cell transplants, compared to only 10 percent following a single transplant. Overall survival was 42 percent for patients treated with a double transplant, compared to only 21 percent for those treated with a single transplant.

Patients who had less than a 50 percent reduction in cancer following induction therapy or the first transplant benefited the most from a second transplant. Patients who had at least a 50 percent anti-cancer response to induction therapy or the first transplant did not appear to benefit from a second transplant. Seventy-eight percent of patients treated with double transplants were able to complete treatment, compared to 82 percent of patients treated with a single transplant.

These authors concluded that patients with newly diagnosed multiple myeloma under the age of 65 years who do not achieve at least a 50 percent reduction in cancer following induction therapy with VAD or a first autologous stem cell transplant appear to achieve significant long-term survival benefit from a second autologous transplant.

Patients with multiple myeloma under the age of 65 who have not responded well to either induction therapy or a first autologous transplant may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating a double transplant.

Campath Produces Responses in Advanced Peripheral T-Cell Lymphoma

According to a recent article published in the journal Blood, the monoclonal antibody Campath® (alemtuzumab) produces anti-cancer responses in patients with peripheral T-cell lymphoma that has stopped responding to standard treatment with chemotherapy.

Peripheral T-cell lymphoma (PTCL) is a rare type of cancer characterized by cancerous T-cells that circulate in the blood and collect in the skin, forming nodules. T-cells are a type of immune cell that are typically involved in the direct attack against foreign cells. Standard treatment for PTCL involves moderate-dose chemotherapy. Although patients may initially respond to treatment with moderate-dose chemotherapy, the majority of patients ultimately experience a return of their cancer. Long-term results for patients with recurrent PTCL are suboptimal and information regarding treatment for these patients is scarce.

Campath is a monoclonal antibody that is approved for patients with B-cell chronic lymphocytic leukemia (CLL) that has recurred following previous therapy. Monoclonal antibodies are proteins with or without carbohydrate portions that can be made in the laboratory and are designed to recognize and bind to very specific fragments or sequences on particular types of cells. Campath recognizes the CD52 antigen (a specific protein located on a cell's surface), which is expressed on normal B and T cells, as well as on abnormal T cells characteristic of peripheral T-cell lymphoma.

Researchers from Germany and Sweden recently conducted a clinical trial to evaluate Campath in the treatment of patients with peripheral T-cell lymphomas who stopped responding to standard chemotherapy. This trial included 14 patients. Following treatment with Campath, 36 percent of patients achieved an anti-cancer response - three patients achieved a complete disappearance (complete remission) of cancer, and two patients achieved a partial disappearance (partial remission) of cancer. The durations of complete remissions were two, six and 12 months. Low blood counts occurred in four patients and infection occurred in eight patients. Five patients died from treatment-related causes in addition to their advanced disease.

The researchers concluded that treatment with Campath produces sustained anti-cancer responses in patients with peripheral T-cell lymphoma that has stopped responding to standard therapies. However, the researchers stated that due to the high rate of side effects associated with treatment, patients with earlier disease and/or younger patients may obtain greater benefit from treatment with Campath, and future clinical trials involving patients with these characteristics are warranted.

Patients with peripheral T-cell lymphoma that has stopped responding to standard therapies may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating Campath or other promising therapeutic approaches.

Reference: Enblad G, Hagberg H, Erlanson M, et al. a pilot study of alemtuzumab (anti-CD53 monoclonal antibody) therapy for patients with relapsed or chemotherapy-refractory peripheral T-cell lymphomas. Blood. 2004;103:2920-2924.

Cryopreserved Ovarian Tissue Results in Live Birth in Hodgkin's Patient

According to a recent article in the Lancet, the cryopreservation of ovarian tissue for six years has resulted in a live birth in a woman who underwent treatment for Hodgkin's disease.

Chemotherapy and radiation therapy are two of the most common treatment modalities for several types of cancer. Unfortunately, chemotherapy and radiation therapy may cause premature menopause in women of childbearing age, leaving them infertile following treatment.

Researchers have been evaluating ways in which to preserve fertility in these women, including cryopreservation (freezing at very low temperatures) and/or re-implantation of specific tissues of the ovaries and/or eggs. Prior clinical studies have demonstrated successful pregnancy and fertility following treatment with chemotherapy and/or radiation therapy by removing parts of the ovaries for cryopreservation and/or reimplantation.

Recently, researchers from Belgium have reported a successful live birth in a patient who had ovarian tissue cryopreserved for six years and then re-implanted into her peritoneum (lining encapsulating the abdomen and pelvis). The patient had been diagnosed with advanced Hodgkin's disease, a type of lymphoma that affects the immune system.

Prior to undergoing treatment with intensive chemotherapy, the patient had tissue removed from her ovaries for cryopreservation. During therapy, the patient became menopausal and was considered infertile. Following therapy, the ovarian tissue was implanted into her peritoneum, resulting in the regaining of fertility and hormonal function. Ultimately, this patient was able to achieve a successful pregnancy and delivery of a normal child.

Results from these studies lead to growing evidence that women of childbearing age who are diagnosed with cancer and must undergo treatment that is associated with high rates of infertility have realistic hope that through cryopreservation and/or reimplantation of ovarian tissue, they may one day experience the healthy birth of a child following treatment.

It is important for women who are diagnosed with cancer and desire children to discuss options for future pregnancy and childbirth with their physician, most optimally prior to initiation of therapy.

Excess AML Risk Greatest 10 Years After Hodgkin Diagnosis

Hodgkin's lymphoma survivors face a more than six-fold excess absolute risk of acute myeloid leukemia (AML), which is highest in the 10 years after Hodgkin's diagnosis, a large new population-based study shows.

The study also found that this excess risk has decreased significantly since 1984, probably due in changes in treatment, but it has not been eliminated.

The relative risk of AML is known to be substantial among Hodgkin's disease survivors, Dr. Sara J. Schonfeld of the National Cancer Institute and colleagues note, but no large study has looked specifically at excess absolute risk of AML in these patients while addressing factors such as age and year of diagnosis.

Dr. Schonfeld and her team looked at 35,511 one-year survivors of the disease included in 14 European and North American cancer registries who had been diagnosed with Hodgkin's lymphoma between 1970 and 2001.

Two hundred seventeen patients developed AML, while 10.8 cases would have been expected, for an unadjusted excess absolute risk of 6.2. Excess absolute risk was 7.9 in the first 10 years of Hodgkin's diagnosis, 4.6 from 10 to 14 years, and 1.3 by 15 years after diagnosis.

The researchers also found that excess absolute risk of AML was higher among patients who were 35 or older when they were diagnosed with Hodgkin's lymphoma compared to those who were younger. Patients diagnosed between 1970 and 1984 also had a greater excess absolute risk of AML than patients diagnosed between 1985 and 2001.

This difference was particularly pronounced for patients who had been treated with chemotherapy initially; these patients overall also showed a greater excess absolute risk of AML.

The chronological decrease in AML risk observed is likely due to changes in chemotherapy, Dr. Schonfeld and her colleagues write. "Analytic studies with detailed treatment data are required to correlate these decreases with changes in therapy and to better understand the long-term risk of AML after Hodgkin's lymphoma," they conclude.

Uncontrolled HIV Load May Increase Risk of Non-Hodgkin Lymphoma

Use of highly active antiretroviral therapy (HAART) for at least 6 months appears to reduce the risk of non-Hodgkin lymphoma (NHL), but uncontrolled viral load increases the risk, AIDS investigators in France report.

Dr. Fabrice Bonnet of Hopital Saint-Andre in Bordeaux and associates conducted a case-control study of 55 patients with AIDS-related B-cell NHL and 145 controls matched for CD4+ cell count, sex, length of follow-up and calendar period. All of the subjects enrolled in Aquitaine Cohort study.

Dr. Bonnet and colleagues' objective was to determine what variables decreased risk of NHL, the most common AIDS-related neoplasia and a leading case of AIDS mortality.

The odds ratio (OR) for neoplasia among patients with at least 6 months of HAART was 0.46 and an undetectable HIV RNA level during follow-up carried an OR of 0.34. In addition to HAART, the use of antiherpetic medication decreased the risk of NHL, with an odds ratio of 0.40.

Age, transmission group, co-infection with hepatitis B or C, peak levels of CD4+ and CD8+ and a history of herpes virus infection were not associated with NHL risk, according to the report, published in the February 1st issue of Clinical Infectious Diseases.

Dr. Bonnet comments that the study "confirms that a minimum duration of 6 months of HAART is required to prevent NHL" and that HIV RNA level "is a possible risk factor for AIDS-related NHL in the era of HAART, independent of immunodeficiency."