Lymphoma

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. The lymphomas are divided into two major categories: Hodgkin lymphoma and all other lymphomas, called non-Hodgkin lymphomas.

Hodgkin lymphoma was named for Thomas Hodgkin, an English physician who described several cases of the disease in 1832. Hodgkin lymphoma will represent about 11.5 percent of all lymphomas diagnosed in 2005.

About 63,740 Americans will be diagnosed with lymphoma in 2005. This figure includes approximately 7,350 new cases of Hodgkin lymphoma (3,980 males and 3,370 females), and 56,390 new cases of non-Hodgkin lymphoma (29,070 males and 27,320 females).

Lymphomas are cancers that begin by the malignant transformation of a lymphocyte in the lymphatic system. The prefix "lymph-" indicates their origin in the malignant change of a lymphocyte and the suffix "-oma" is derived from the Greek word meaning "tumor".

Lymphomas, including Hodgkin lymphoma, result from an acquired injury to the DNA of a lymphocyte. Scientists know that the damage to the DNA occurs after birth and, therefore, is acquired rather than inherited. The change or mutation of DNA in one lymphocyte produces a malignant transformation. This mutation results in the uncontrolled and excessive growth of the lymphocyte, and confers a survival advantage on the malignant lymphocyte and the cells that are formed from its multiplication. The accumulation of these dividing cells results in the tumor masses in lymph nodes and other sites.

Lymphomas generally start in lymph nodes or collections of lymphatic tissue in organs like the stomach or intestines. Lymphomas may involve the marrow and the blood in some cases. Spread from a lymphoma site is not unexpected. Lymphocytic leukemias originate and are most prominent in the marrow and spill over into the blood. They occasionally spread to involve the lymph nodes.

Causes and Risk Factors
The annual incidence of lymphoma has nearly doubled over the last 35 years. The reasons for this increase are not certain and are probably multiple. Immune suppression plays a role in some patients. Persons infected with the human immunodeficiency virus (HIV) have a much higher risk of developing lymphoma. The Epstein-Barr virus causes Burkitt lymphoma in Africa. The bacterium Helicobacter pylori is associated with the development of lymphoma in the stomach wall. These risk factors explain only a small proportion of the cases.

The principle cause of the increase in lymphoma is unknown. There is an apparent increase in lymphoma incidence in communities where farming is prevalent. Studies point to specific ingredients in herbicides and pesticides as being associated with lymphoma occurrence, but the quantitative contribution of such exposures to the frequency of lymphoma has not been defined.

The cause of Hodgkin lymphoma is uncertain. Many studies of environmental, especially occupational, linkages have been conducted with ambiguous results. For example, woodworking exposure has been associated with the disease, but causality has not been established. The Epstein-Barr virus has been associated with about one-third of cases of the disease. It has not been established conclusively as a cause of Hodgkin lymphoma, however. Persons infected with HTLV and HIV also have an increased probability of developing Hodgkin lymphoma.

Incidence
In the United States, non-Hodgkin lymphoma is the sixth most common cancer among males and the fifth most common cancer among females. The age-adjusted incidence of non-Hodgkin lymphoma rose by 71 percent from 1977 to 2002, an annual percentage increase of nearly 2.7 percent.

Age-specific incidence rates of non-Hodgkin lymphoma are 3.0/100,000 at ages 20-24 for males and 1.9/100,000 for females. By ages 60-64, they are 51.5/100,000 for males and 37.5/100,000 for females.

The incidence of Hodgkin lymphoma among people under 20 years of age was 1.2 per 100,000 people in 2002.

Leukemia

The major forms of leukemia are divided into four categories. Myelogenous and lymphocytic leukemia each have acute and chronic forms. The terms myelogenous or lymphocytic denote the cell type involved.

Acute leukemia is a rapidly progressing disease that affects mostly cells that are unformed or primitive (not yet fully developed or differentiated). These immature cells cannot carry out their normal functions.

Chronic leukemia progresses slowly and permits the growth of greater numbers of more developed cells. In general, these more mature cells can carry out some of their normal functions.

Thus, the four major types of leukemia are: acute or chronic myelogenous, and acute or chronic lymphocytic leukemia.

Major Types of Leukemia

Acute Myelogenous Leukemia
Acute Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Chronic Lymphocytic Leukemia


The ability to measure specific features of cells has led to further subclassification of the major categories of leukemia. The categories and subsets allow the physician to decide what treatment works best for the cell type and how quickly the disease may develop.

48,000 Messages to Congress - You Made A Difference

When President Bush delivered his FY 2007 budget proposal to Congress in February, his plan included significant cuts to funding for the National Institutes of Health (NIH), National Cancer Institute (NCI) and Centers for Disease Control and Prevention (CDC).

If ratified, the proposal would reduce the total number of NIH-funded research grants by two percent, slashing nearly 650 research projects. Another $40 million would be cut from funding for medical research at the NCI. In addition, the President's budget proposes deep reductions at the CDC for chronic disease prevention, quality-of-life programs and health promotion. Specifically, the proposal cuts nearly $20 million from chronic disease programs, which include cancer control, prevention and survivorship.

In March, the Lance Armstrong Foundation (LAF) alerted you that Congress was considering the first cuts to these critically important healthcare budgets in 40 years. We gave you the facts and asked you to take action by contacting your representatives in Washington and letting them know that the fight against cancer deserves more, not less. And you did.

In just a matter of days, LAF Advocacy Team members and others spoke loud and clear by sending their Congressmen and women more than 48,000 messages opposing the recommended funding cuts.

Thanks in part to the strong support of the LAF Advocacy Team, on Thursday, March 16, the United States Senate voted 63 to 37 in favor of a bipartisan amendment to the Senate budget resolution restoring $7 billion in funding for education and health programs. Sponsored by Senators Arlen Specter (R-PA) and Tom Harkin (D-IA), the amendment reinstates funding to critical medical research and public health programs at NIH and the CDC.

See how your Senators voted.

Though we can celebrate victory in the Senate, there is a long road ahead and much work to be done. The House budget process is currently at an impasse as lawmakers recently left for a two-week spring recess without completing their version of the budget resolution. The House Leadership has indicated that negotiations will likely resume when legislators return the week of April 24.

While there are no guarantees in the legislative process, there would have been no hope of increased funding for cancer research and programs this year without passage of the Specter-Harkin amendment in the Senate. We will continue to work with members of Congress to ensure cancer research and public health programs receive the necessary funding.



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Federal Study Rejects Aspartame Risks

A huge federal study in people — not rats — takes the fizz out of arguments that the diet soda sweetener aspartame might raise the risk of cancer.

No increased risk was seen even among people who gulped down many artificially sweetened drinks a day, said researchers who studied the diets of more than half a million older Americans.

A consumer group praised the study, done by reputable researchers independent of any funding or ties to industry groups.

"It goes a fair way toward allaying concerns about aspartame," said Michael Jacobson, head of the Center for Science in the Public Interest, which had urged the government to review the sweetener's safety after a troubling rat study last year.

Findings were reported Tuesday at a meeting of the American Association for Cancer Research.

Aspartame came on the market 25 years ago and is found in thousands of products — sodas, chewing gum, dairy products and even many medicines. NutraSweet and Equal are popular brands.

Research in the 1970s linked a different sweetener, saccharin, to bladder cancer in lab rats. Although the mechanism by which this occurred does not apply to people and no human risk was ever documented, worries about sugar substitutes in general have persisted.

They worsened after Italian researchers last year reported results of the largest animal study ever done on aspartame, involving 1,800 lab rats. Females developed more lymphomas and leukemias on aspartame than those not fed the sweetener.

The new study, by scientists at the National Cancer Institute, involved 340,045 men and 226,945 women, ages 50 to 69, participating in a research project by the National Insitutes of Health and AARP, formerly known as the American Association of Retired Persons.

From surveys they filled out in 1995 and 1996 detailing food and beverage consumption, researchers calculated how much aspartame they consumed, especially from sodas or from adding the sweetener to coffee or tea.

Over the next five years, 2,106 developed blood-related cancers such as lymphoma or leukemia, and 376 developed brain tumors. No link was found to aspartame consumption for these cancers in general or for specific types, said Unhee Lim, who reported the study's findings.

The dietary information was collected before the cancers developed, removing the possibility of "memory bias" — faulty recollection influenced by knowing you have a disease.

"It's very reassuring. It's a large study with a lot of power," said Richard Adamson, a senior science consultant to the American Beverage Association, the leading industry group.

The Center for Science in the Public Interest still warns about one potential hazard of aspartame use: thinking that calories "saved" from using a sugar substitute justify "spending" more on unhealthy foods.

"Drinking a diet soda at lunch does not mean it's okay to have a larger dessert at dinner," the group's Web site warns.

Patients with Stage IV Follicular Lymphoma Are Living Longer

Researchers at the M.D. Anderson Cancer Center in Texas evaluated trends over time in the survival of patients with stage IV follicular lymphoma; they found that survival improved notably between 1972 and 2002.

Non-Hodgkin’s lymphoma (NHL) 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, which exist in two forms: B and T-cells. Each of these cells has a specific function in fighting 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. NHL is categorized by the type of lymphocyte it involves and by the rate at which the cancer grows—both are determined by the cells’ appearance under a microscope.

Follicular lymphoma is considered a low-grade or indolent lymphoma, which means that it is a slow-growing subset of NHL. Although patients with advanced follicular lymphoma may survive for many years, the disease is generally considered incurable.

Because treatment of follicular NHL has evolved, researchers at the M.D. Anderson Cancer Center in Texas evaluated how survival has changed over time. They assessed 580 patients who were treated for stage IV follicular lymphoma between 1972 and 2002. Treatment varied during this period. Patients in the most recent time period (1997 to 2002) were treated with FND (fludarabine, mitoxantrone, and dexamethasone) with concurrent or sequential rituximab followed by interferon.

Researchers observed improved survival over time:

Between 1972 and 2002, the proportion of patients surviving for at least five years increased from 64% to 95%.
The proportion of patients surviving for at least five-years without lymphoma relapse or progression increased from 29% to 60%.
The researchers conclude that newer approaches to treatment have resulted in improved survival among patients with stage IV follicular lymphoma.

Reference: Liu Q, Fayad L, Cabanillas F et al. Improvement of Overall and Failure-Free Survival in Stage IV Follicular Lymphoma: 25 Years of Treatment Experience at the University of Texas M.D. Anderson Cancer Center. Journal of Clinical Oncology . 2006;24:1582-1589.

Rituximab Effective Against Chronic Graft-Versus-Host Disease

Rituximab is effective in treating transplant patients with chronic graft-versus-host disease (GVHD) that is refractory to corticosteroid therapy, according to a report in the March 21 online edition of Blood.

"We would like physicians to consider using this compound for patients with chronic GVHD, particularly those with musculoskeletal and cutaneous involvement," Dr. Corey Cutler from Dana-Farber Cancer Institute, Boston, Massachusetts told Reuters Health. "This is where we noted the drug to be most active."

Dr. Cutler and colleagues investigated the effectiveness of rituximab in 21 patients with clinically extensive chronic GVHD that had not responded to treatment with corticosteroids and at least one other form of systemic immunosuppression.

Circulating CD19 B cells became undetectable by eight weeks after commencing rituximab therapy and remained undetectable in all patients for at least one year, the researchers report. Median circulating levels of IgG and IgM also fell significantly by week 16 after rituximab therapy.

Fourteen of 20 patients showed objective responses to rituximab, the results indicate, including two subjects with a complete clinical response. About two thirds of the patients had a dose reduction of at least 50% in corticosteroid doses.

Median body surface involvement of cutaneous GVHD fell by more than one half at one year, the investigators observe, and there were significant improvements in rheumatologic visual analog scales for pain and fatigue.

Patients with significant ocular or oral mucosal manifestations of GVHD did not show significant clinical responses, the researchers note.

All four patients with demonstrable H-Y antibodies showed clinical responses to rituximab therapy, the report indicates, including one patient who had a complete response and was able to discontinue all immunosuppressive and another patient who was able to discontinue corticosteroids and continues to follow a tapering course of other immunosuppressive.

"The clinical effectiveness of rituximab in chronic GVHD implicates the B cell system in the complex process of chronic GVHD," Dr. Cutler pointed out. "Its usefulness certainly does not exclude the T cell system, but makes us believe that there is a complex interplay between multiple elements of the immune system in the pathophysiology of chronic GVHD."

Dr. Cutler said his group is working with the Bone Marrow Transplant Clinical Trials Network on a trial that will test rituximab as initial therapy for chronic GVHD. "In addition, we have begun a clinical trial of rituximab as prophylaxis against chronic GVHD at our center."

Blood 2006.

Rituximab Enhances Chemotherapy in Lymphoma Patients

In young and relatively young lymphoma patients, addition of the monoclonal antibody, rituximab, to standard chemotherapy improves survival, researchers report in an April 5th online edition of The Lancet Oncology.

Dr. Michael Pfreundschuh of Saarland University Medical School, Hamburg, Germany and colleagues note that rituximab along with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP)-like chemotherapy has proved successful in elderly patients.

To investigate whether this might also be the case in those aged 18 to 60 years, the researchers studied 824 such patients with good-prognosis CD20-positive diffuse large B-cell lymphoma.

They were randomized to 6 cycles of CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites were treated with radiotherapy.

Three-year event-free survival rates were 79% among patients in the combination group, versus 59% of those given CHOP alone. For overall survival, the corresponding rates were 93% and 84%.

In the CHOP group there were 57 lymphoma-associated and one treatment-related death. In the combination group, there were 19- lymphoma-associated and 6 treatment-related deaths.

An age-adjusted International Prognostic Index (aaIPI) score of zero and lack of bulky disease was associated with a better prognosis than was the case for those without either or both of these favorable factors.

Dr. Pfreundschuh told Reuters Health that "while the results of the very favorable subgroup... can hardly be improved any further, the results in the less favorable subgroup -- all patients with aaIPI=1, and patients with aaIPI=0 and bulky disease -- definitely need further improvement."

Nonetheless, say the investigators, the effect of rituximab overall was greater than that expected on the basis of the earlier results in elderly patients. In fact, the team concludes that the need for salvage therapy in these younger patients "could be halved by the addition of rituximab."

Lancet Oncol 2006.

Nicotine Interferes with Chemotherapy, Study Finds

Nicotine can prevent chemotherapy drugs such as Taxol from killing lung cancer cells, researchers reported on Sunday in a finding that may help explain why lung cancer is so difficult to treat in smokers.

They said their findings may also suggest that even people who quit smoking but use nicotine supplements, such as patches or gum, may not be helped as much as they should be by cancer therapy.

"Our findings are in agreement with clinical studies showing that patients who continue to smoke have worse survival profiles than those who quit before treatment," the researchers wrote in a study published by the Proceedings of the National Academy of Sciences.

Srikumar Chellappan and colleagues at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, tested three standard lung cancer drugs: gemcitabine, cisplatin and Taxol, on several different batches, called cell lines, of cells taken from lung cancer tumors.

Adding a small amount of nicotine, equivalent to what would be found in the blood of an average smoker, interfered with the drugs' action against the tumor cells, they reported in the study, which was also presented to a meeting of the American Association for Cancer Research.

Nicotine protected the cancer cells by increasing the activity of two genes called XIAP and survivin, Chellappan's team found. The genes stopped a process called apoptosis, a kind of cell suicide.

When the two genes were suppressed, the cells died as they should have, they said.

Stem cell transplants can be effective, but expensive

Experts say stem cell transplants are growing as an effective last resort for cancer treatments, but their affordability may be out of reach for some.

Tara Guevara-Stover, 28, of Vestal, needs the transplant to save her life, but the high costs of new treatments and medications will put her deep in debt.

"I have a lot of bills that are due because I can't pay everything," Guevara-Stover said.

When she was diagnosed with cancer in 2004, she was five months pregnant, and her biggest concern was her child.

Her son, Joey, wasn't affected by the chemotherapy she received before his birth, but her cancer has gotten worse and warrants a stem cell transplant. Now one of her major concerns is money.

Guevara-Stover must pay to find a donor for a stem cell transplant.

According to the National Cancer Institute, only about a third of patients will find a match in their family, but 50 percent find non-related donors, usually through the National Marrow Donor Project. Doctors use the registry to find matches, but there's a cost between $200 and $300 per donor because of blood tests.

Dr. Joseph Readling of Broome Oncology said stem cell transplants are used for treating leukemia and lymphoma, and have a one-year survival rate between 40 and 50 percent nationwide, though results vary depending on the type of cancer and various risk factors, such as age or health.

Dave Born, 53, of Spencer, said the bill for his treatment at the Nebraska Medical Center was well over $200,000. Born said the bill was lower than it could have been had the insurance company not contracted with the hospital for a lower rate; plus, his wife took on minor nursing duties, among other things.

Born had a transplant at the Nebraska Medical Center in 2003 at the suggestion of his insurance company, which covered the entire procedure and living expenses.

Guevara-Stover's insurance will cover only 85 percent of the procedure and does not cover the cost of finding a donor. She has contacted the Leukemia & Lymphoma Society for help with the bills, though she said the organization can provide only limited assistance.

"It shouldn't be that way for life-saving techniques," she said.

Stem cells are used to reconstitute the immune systems of patients by eliminating cancer-producing cells and adding healthy cells that will kill tumors. The cells come from three sources: patients' own bone marrow, bone marrow from donors or placentas.

Bone Marrow Transplant Disease Predictable: Study

Researchers can predict which bone marrow transplant patients will likely develop a deadly complication a week after the procedure and well before any symptoms occur, according to a study released on Friday.

Researchers at the University of Michigan Comprehensive Cancer Center found that elevated levels of a protein called tumor necrosis factor, or TNF, measured a week after patients received bone marrow transplants, were found among those who later developed the deadly complication called graft vs. host disease.

"This suggests we could target patients to prevent graft vs. host disease based on their post-transplant level of TNF. If we can develop a test that can reliably predict this complication, we can then look at treating it before symptoms develop," said the study's author, John Levine.

While bone marrow transplants offer hope for people with certain cancers that no longer respond to conventional treatment, as many as half of the patients who undergo the procedure develop graft vs. host disease, with about 30 percent of transplant patients dying from it.

It is a deadly condition in which transplanted immune cells attack the patient's skin, liver and gastrointestinal cells and ultimately can trigger a massive inflammatory reaction that can kill the patient.

The study, presented at the American Society for Blood and Marrow Transplant's annual meeting in Honolulu, looked at 170 patients, 94 of whom went on to develop graft vs. host disease. Those 94 patients had elevated levels of the tumor necrosis factor protein a week after their transplants.

Researchers also found that patients whose TNF level was elevated at seven days had a 20 point lower survival rate: 62 percent were alive after a year, compared with 85 percent of those patients with a lower TNF level.

"This is one small step in a long road to making transplants safer and more effective," said Levine.

Omega-3 Fatty Acids Do Not Lower Cancer Risk

Taking dietary supplements containing fish oil (omega-3 fatty acids) or regularly consuming fish does not appear to reduce a person's risk of developing cancer, according to a report in the Journal of the American Medical Association. However, lead investigator Catherine H. MacLean said consumers should consider the other health benefits of omega-3 fatty acids before deciding whether to take dietary supplements containing omega-3 fatty acids or to eat more fish.