New cancer treatment which reprograms cells to self-destruct gives hope for lung patients

A new treatment for cancer which kills cancerous cells and leaves healthy ones untouched could revolutionise treatment, scientists have claimed.
Unlike healthy cells, which eventually self destruct once no longer useful, cancer cells dodge this suicide path.
Instead the cells grow out of control, causing tumours to form.
The scientists, based at the UCL Cancer Institute, believe they have fixed this fault in lung cancer cells, by reprogramming the cells to self destruct.
Through using lung cancer cells and mice, the scientists showed that the combination of two drugs, TRAIL and a CDK9 inhibitor, changed the molecular modifications in the cell suicide process, forcing the cancer cells to self-destruct.
This new drug combination, which will be presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool next week, could pave the way for new treatments.
However the researchers stressed that the drug combination is in early stage development, to potentially treat non small cell lung cancer.
Nell Barrie, senior science information manager at Cancer Research UK, added: "This important research builds on the progress we've made to understand the routes cancer cells use to stay alive.
"Understanding and targeting these processes will move us closer to our goal of three out of four people beating cancer within the next 20 years.
"There's an urgent need to save more lives from lung cancer and we hope these findings will one day lead to effective new treatments to help lung cancer patients and potentially those with other cancer types too."

Breast Cancer and Chemotherapy

When it comes to responding to chemotherapy, not all breast cancers are created equal. So far, doctors have not been able to accurately predict which women would derive added benefits from chemotherapy and which ones wouldn't. So the policy has often been, "When in doubt, get chemotherapy."

Now, studies show that a new genetic test, known as the Oncotype DX 21-gene assay, not only assesses the likelihood of breast cancer recurrence for many early-stage breast cancer patients, but also predicts how much chemotherapy will help these women. This new test may give some low-risk women the option of skipping the rigors of chemotherapy, while reassuring others that the often-difficult treatment they're receiving has a clearly defined benefit.

For women who have hormone-positive breast cancer that has not yet spread to the lymph nodes, the Oncotype assay analyzes 21 genes related to breast cancer in the body that breast cancer cells depend on, including the estrogen receptor, HER2 and proliferation genes. It then divides the results into low-, medium-, and high-risk scores.

Women in the low-risk group, about half the patients studied, would get only a minimal, if any, benefit from chemotherapy. Women in the high-risk group would be very likely to benefit from chemotherapy.

Herceptin Clinical Trials for Breast Cancer

Four large-scale, randomized clinical trials are now under way to better identify the benefits and risks of Herceptin. "It's very likely that Herceptin will be an effective therapy in early-stage disease, based on what we've seen in metastatic breast cancer," says Sloan-Kettering's Hudis. "But what's not so clear yet is how big an impact it will have on survival and recurrence rates, and what the price might be for a broad population in terms of heart failure. If we improve survival rates by 2%, but it causes 4% of patients to have significant heart failure, then you'd have a hard time figuring out what to do next."

In the small group of study patients at M.D. Anderson who received Herceptin, says Buzdar, none so far has developed any heart problems almost two years after treatment. Some doctors have prescribed Herceptin "off-label" for women with non-metastatic breast cancer, but both Hudis and Isaacs are cautious. They recommend women with early-stage breast cancer only take Herceptin if they are in a clinical trial until more questions are answered about the drug's risks and benefits.

Herceptin in the Treatment for Breast Cancer

For several years, the drug Herceptin has been used to treat women with HER2-positive breast cancer that has metastasized or recurred. It's a kind of drug known as a monoclonal antibody. It works like a heat-seeking missile, homing in on cells that make too much HER2neu protein. Used either with chemotherapy or alone, Herceptin can reduce tumor size and increase a woman's chances of both overall survival and disease-free survival.

But the trials that led to Herceptin's FDA approval were all in women with advanced breast cancer. Would Herceptin work as well in women with early-stage disease? Within the last year, promising research has indicates the answer may be yes.

In a study released last June, scientists at the University of Texas M.D. Anderson Cancer Center in Houston looked at women with early-stage, HER2-positive breast disease. They found that more than twice as many women who received Herceptin as part of their presurgical chemotherapy had their tumors completely disappear compared with women who received chemotherapy alone. Indeed, the results were so striking that the researchers stopped the study early, after enrolling only 42 of a planned 164 patients.

"More than 65% of the Herceptin patients had a complete response rate, as compared with only 26% of patients who received chemotherapy only," says Aman Buzdar, MD, deputy chair of the department of breast and medical oncology at the M.D. Anderson Cancer Center.

So why hasn't Herceptin been approved for use in early-stage HER2-positive breast cancer yet? First, because of the relatively small size of the trial, and second, because of concerns about its side effects. In a small percentage of patients, Herceptin can cause heart damage and sometimes even heart failure.

Aromatase Inhibitors

Aromatase inhibitors aren't new. The FDA approved the first, Arimidex, in September 2000. Many large trials have recently confirmed that these hormone therapies outperform the more commonly used tamoxifen to prevent tumor recurrence in women who had hormone-positive breast cancers (cancers that are fed by estrogen).

Because they act only on estrogen that's produced outside the ovaries, aromatase inhibitors are only effective in postmenopausal women. (Before menopause, most of the body's estrogen is produced in the ovaries.) But for these women, Arimidex and its sister drugs, like Aromasin and Femara, offer a small but crucial advantage over tamoxifen -- 4% to 5% -- in preventing cancer recurrence. Researchers still don't know which strategy works best: taking an aromatase inhibitor instead of tamoxifen, as the first course of therapy after surgery for breast cancer (called adjuvant therapy) or beginning treatment with tamoxifen and switching to an aromatase inhibitor after two to five years.

Other factors involved with Abraxane

Another factor could be involved. Because albumin, which normally transports nutrients to cells, accumulates in rapidly growing tumors, it's possible that the bundles of Abraxane in their albumin "envelopes" are sent by express delivery directly to cancer cells. "There are signs indicating that albumin receptors in breast cancer and other cancer cells would preferentially pick up these albumin-bound packets."

If so, that may have exciting implications for other chemotherapy drugs used in breast and other cancers, says Claudine Isaacs, MD, director of the Clinical Breast Cancer Program at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center in Washington, D.C. "This delivery system probably will not be limited to paclitaxel. Theoretically, you could put any number of chemotherapy drugs in these packets, not just paclitaxel." And years of experience with chemotherapy show that delivery matters. "The same drug can have a very different side effect profile, as well as potentially different benefits and response rates, based on how it's delivered."

So far, Abraxane has only been FDA-approved for use in patients with breast cancer that has recurred or metastasized. Still, many drugs that are first approved for use in this stage of the disease later prove to be effective for women with earlier-stage breast cancer.

New Treatments for Breast Cancer

Paclitaxel, commonly marketed as Taxol or Taxotere, is part of many chemotherapy drug regimens, but it has one big problem, says Clifford Hudis, chief of the Breast Cancer Medicine Service at New York's Memorial Sloan-Kettering Cancer Center. "It doesn't dissolve in water, which means we have to put the drugs in solvents to deliver them to patients." Those solvents can cause a number of side effects, including severe allergic reactions. Patients taking paclitaxel have to receive heavy doses of other medications first, such as steroids and antihistamines, before getting their chemotherapy.

Abraxane does a neat end run around that problem. A process called protein-bound nanoparticle technology creates tiny particles that bind the paclitaxel to a naturally occurring protein called albumin. "The binding makes little packets of paclitaxel, think of them as little bubbles, that can be dissolved in water," says Hudis. This means no more solvent, which in turn means no more medications before chemotherapy, and no more of the side effects that go along with them. It's also shortened the chemotherapy's infusion time from more than three hours to around half an hour.

These practical pluses would be enough to make anyone receiving chemotherapy rejoice. But there may also be a bonus in terms of the drug's effectiveness. In one of the major clinical trials that led to Abraxane's FDA approval, women who got this drug had almost twice the response rate to chemotherapy compared with women who received regular Taxol. This may be in part because without the need for solvents, higher doses of paclitaxel could be delivered to the women getting Abraxane.

New Iridium- based Drug for Chemo Therapies

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.
"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by patients" argues Professor Sadler.
This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

Cancer treatment revolution potential with new drug

A new study at the University of Warwick, published in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.
Called ZL105, the drug is a compound based on the precious metal iridium. The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.
Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."
Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.
Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

Novartis, Juno Conduct New Studies on Leukemia Therapies

“CAR T cells are probably one of the most exciting concepts and fields to come out in cancer in a very, very long time,” says Dr. Daniel DeAngelo, a Boston-based hematologist and associate professor of medicine at Harvard Medical School.

Usman Azam, head of cell and gene therapies at Novartis, calls the therapies “critically important” for Novartis. “I think that a cure for cancers such as leukemia and lymphoma through a CAR technology is plausible,” said Dr. Azam . “Our job is to get this into patients as soon as we feasibly can.”

Dr. Azam heads a new unit Novartis created partly to speed the therapies’ time to market. Its leading CAR therapy was granted ‘breakthrough’ designation by the U.S. Food and Drug Administration in July, and Novartis wants to file it with regulators in 2016.

CAR therapies are a mixture of genetic tweaking and “immunotherapy,” or using the patient’s own immune system to fight disease. They involve extracting disease-fighting white blood cells called T-cells from a patient’s blood. The T-cells are then genetically modified, grown in a laboratory for around 10 days and reinjected into the patient.

Typically, the T-cells are combined with a disabled virus, which enables them to produce chimeric antigen receptors, or CARs, that recognize and target malignant proteins on a cancer cell’s surface.

Novartis and Juno are developing their treatments in partnership with top academic teams: Novartis with the University of Pennsylvania and Juno with teams at Memorial Sloan-Kettering Cancer Center in New York, Seattle Children’s Hospital and the Fred Hutchinson Cancer Research Center, also in Seattle.

Doctors Excited by New Cancer Treatment

“Molecularly Targeted Therapy.” The treatment consists of drugs designed at the molecular level of the cell to specifically attack and kill only the cancer cells of a specific type of cancer. And they are tailor-made to recognize specific molecules unique to specific cancers.

The model drug leading the way is Glivec, also known as STI571. It is active against a relatively rare form of leukemia, chronic myeloid leukemia, or CML characterized by excessive overproduction of white blood cells. Approximately 7,000 Americans are diagnosed with CML each year.

Doctors are extremely hopeful that the drug could provide a model for similar drugs to treat cancers affecting many thousands more people. This year, alone, some 1.3 million Americans will be diagnosed with cancer.

“This is as important as it gets. A cancer-specific target, a drug specifically designed for the target, the most effective agent ever,”says Paul A. Bunn Jr., president-elect of the American Society of Clinical Oncology. “Read my lips, this is real, not mice.”

Dr. Brian Druker, director of the Leukemia Program at the Oregon Health Sciences University in Portland, is the main researcher on the drug, which is being developed by Novartis Pharmaceuticals.

Merck’s New Drug Seen As Breakthrough in Cancer Treatment

WEST POINT, Pa. (CBS) — Area oncologists are hailing the FDA’s approval of a new cancer drug developed by Merck, which has a large facility in Montgomery County.
The drug, a new form of immuno-therapy is called Keytruda.  And it’s being called a game changer in the field of cancer treatment.
The drug has been approved for use against melanoma, but Dr. Hossein Borghaei, of Fox Chase Cancer Center, says similar treatments are being developed to control other forms of cancer.
“We now have at least preliminary report that immuno-therapy can be very effective in lung cancer,”   “There are many different companies working on developing drugs that, in essence, are thought of as taking the brake off the immune system, to allow the patients own immune system to recognize the tumor as foreign and to try to control the disease that way.”
Bristol Myers expects to file for FDA approval of its new drug to treat melanoma by the end of the month.

Bone marrow transplants

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.
Bone marrow is the soft, fatty tissue inside your bones. Stem cells are immature cells in the bone marrow that give rise to all of your blood cellsThere are three kinds of bone marrow transplants:

• Autologous bone marrow transplant: The term auto means self. Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer (cryopreservation). After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make (regenerate) normal blood cells. This is called a rescue transplant.
• Allogeneic bone marrow transplant: The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match your genes. Special blood tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you may be found through national bone marrow registries.
• Umbilical cord blood transplant: This is a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for matching. But blood counts take much longer to recover.

What causes swollen glands?

The most common causes of swollen glands include:

• Bacterial infection, such as strep throat.
• Mouth sores or tooth infection.
• Viral infection, such as mononucleosis  or "mono."
• Skin infection.
• Ear infection.
• Sexually transmitted disease.
• Cancers such as leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, and breast cancer.
• Immune system disorders, such as lupus, rheumatoid arthritis, and HIV infection.
• Side effect from a vaccine or from certain medications.

What increases the risk of getting Non-Hodgkins Lymphoma?

No one knows exactly what increases your risk of getting non-Hodgkin's lymphoma (NHL). Experts do agree that the disease is not caused by injury and is not contagious. The following risk factors may increase your chances of having the disease. But most people with these risk factors do not ever have non-Hodgkin's lymphoma, and many people who have non-Hodgkin's lymphoma do not have any of these risk factors.²

• Being male. NHL is more common in men than in women.
• Age. The likelihood of getting NHL increases as you get older.
• Impaired immune system. NHL is most common among those who have an impaired immune system, an autoimmune disease, or HIV or AIDS. It also occurs among those who take immunosuppressant medicines, such as medicines following an organ transplant.
• Viral infection. A viral infection, such as Epstein-Barr virus, increases the risk of developing NHL.
• Bacterial infection. Infection with Helicobacter pyloriincreases the risk of lymphoma involving the stomach.
• Environmental exposure. Exposure to agricultural pesticides or fertilizers, solvents and other chemicals, rubber processing, asbestos, and arsenic increases the risk of developing NHL.

The survival rate and prognosis for Hodgkin's Lymphoma

The five-year survival rate refers to the percentage of patients, according to the stage of their disease at diagnosis, who live at least five years after treatment for Hodgkin lymphoma. Many of these patients live longer than five years.

• Stage I: 90%-95%
• Stage II: 90%-95%
• Stage III: 85%-90%
• Stage IV: about 80%

Long-term health problems can occur after treatment of Hodgkin lymphoma that are related to the treatment -- leukemia, myelodysplastic syndromes, breast cancer, heart disease, thyroid disease, lung disease, including lung cancer, and infertility. Annual physical exams are essential to screen for other diseases. Tests might include annual breast MRI scans and/.or annual chest CT scans. Medical  attention should be sought, promptly, for any new, serious symptoms.

What happens to a person with Non-Hodgkin's Lymphoma

In non-Hodgkin's lymphoma (NHL), either abnormal cells in the lymphatic system divide and grow without order or control or old cells do not die normally. Lymphatic tissue is present in many areas of the body, so non-Hodgkin's lymphoma can start almost anywhere in the body.
Non-Hodgkin's lymphoma may occur in a single lymph node, a group of lymph nodes, or an organ. And it can spread to almost any part of the body, including the liver, bone marrow, and spleen. Doctors classify NHL into stages based on where the lymphoma is growing in the body.
Over time, lymphoma cells may replace the normal cells in the bone marrow. Bone marrow failure results in the inability to produce red blood cells that carry oxygen, white blood cells that fight infection, and platelets that stop bleeding.
Long-term survival depends on the type of non-Hodgkin's lymphoma and the stage of the disease when it is diagnosed. Approximately 81 out of 100 people diagnosed with non-Hodgkin's lymphoma are alive 1 year after the disease is diagnosed. That number drops to about 63 out of 100 at 5 years and 49 out of 100 at 10 years.

Knowing if I have Hodgkin's Lymphoma

The diagnosis of Hodgkin lymphoma can only be made by a tissue biopsy -- cutting a tissue sample for examination. If you have an enlarged, painless lymph node that your doctor suspects may be due to Hodgkin lymphoma, tissue will be taken for biopsy or the entire node will be removed. The diagnosis of Hodgkin lymphoma can be confirmed if a type of cell, called a Reed-Sternberg cell, is seen.

If a biopsy reveals that you do have Hodgkin lymphoma, you may need additional tests to determine the extent, or stage, of the disease. Tests include blood tests, chest X-ray, computed tomography (CT) scans of the chest, abdomen and pelvis, and possibly the neck, and a PET scans. Magnetic resonance imaging (MRI) scans, bone scans, spinal tap (lumbar puncture), and bone marrow studies are useful under special circumstances.
These tests will confirm the stage of the disease and the best type of therapy to pursue. 

Other Non-Hodgkin Lymphoma risk factors

• Chemical exposure:  arsenic, lead, vinyl chloride, asbestos, insecticides, pesticides and weed killers, wood preservatives, organic chemicals, and solvents
• Exposure to nuclear accidents,  nuclear testing, or underground radiation leaks
• Treatment with immunosuppressant drugs, for prevention of organ transplantation rejection, or for treatment of inflamatory and autoimmune disorders
• Tumor necrosis factor agents used to treat psoriatic and rheumatoid arthritis and inflammatory bowel disease
• Prior exposure to chemotherapy and/or radiation used to treat a prior diagnosis of  cancer
• Treatment with a medication called Dilantin (phenytoin), commonly used to treat seizure disorders
• Use of hair dyes, especially dark and permanent colors, used before 1980
• High levels of nitrates found in drinking water
• Diets high in fat and meat products
• Ultraviolet light exposure
• Alcohol intake

What causes Non-Hodgkin's Lymphoma?

The exact cause of non-Hodgkin lymphoma is unknown. However, there are multiple medical conditions that are associated with an increased risk of developing non-Hodgkin lymphoma:

• Inherited immune deficiencies: ataxia-telangectasia, Wiskott-Aldrich syndrome, common variable immunodeficiency, severe combined immunodeficiency, and X-linked lymphoproliferative syndrome
• Genetic syndromes: Down syndrome, Klinefelter's syndrome (a genetic condition in men caused by an extra X chromosome)
• Immune disorders, and their treatments: Sjögren's syndrome (an immune disorder characterized by unusual dryness of mucus membranes), rheumatoid arthritis, systemic lupus erythematosus
• Celiac disease, a disease involving the  processing of certain components of gluten, a protein in grains
• Inflammatory bowel disease, particularly Crohn’s disease, and its treatment
• Psoriasis
• Family history of lymphoma
• Bacteria: Helicobacter pylori, asssociated with gastritis and gastric ulcers; Borrelia burgdorferi, associated with Lyme disease; Campylobacter jejuni; Chalmydia psittaci
• Viruses: HIV, HTLV-1, SV-40, HHV-8, Epstein Barr virus, hepatitis virus
• Non-random chromosomal translocations and molecular rearrangements

Other complications from Chest Radiation

Other complications from chest radiation include:

• A higher risk of breast cancer
• Inflammation and scarring of lung tissue (called radiation pneumonitis)
• Heart problems, such as narrowing of the coronary arteries and heart failure
• Inflammation and scarring of the lining around the heart (called pericarditis)

The risk of complications from radiation increases when the person is treated with chemotherapy and radiation therapy. The combination increases the risk of other cancers, including:

• Leukemia, a cancer of the white blood cells
• Other types of lymphomas called non-Hodgkin lymphoma
• Non-melanoma skin cancer

In the past, radiation was used on some tissues and organs in the abdomen. This could damage the kidney, leading to kidney failure and high blood pressure. This tends to be uncommon today, as radiation to this area is less frequently used.

Other side effects from chest radiation may include dry mouth, mouth sores and difficulty swallowing.

Complications from Radiation Therapy

There are some complications from using radiation therapy to treat Hodgkin's disease.

Most commonly, radiation is used in the chest area. This area, called the "mediastinum," is often involved with Hodgkin's disease.

The most common organ adversely affected by chest radiation is the thyroid gland. Radiation can damage thyroid cells that make thyroid hormone. This may lead to lower than normal blood levels of thyroid hormone (called hypothyroidism). Radiation also increases the risk of developing thyroid cancer.

People who have radiation to the chest need to be monitored for thyroid abnormalities for the rest of their lives.

Types that Hodgkin's Affects

Hodgkin disease is most common in two different age groups: young adults (ages 15 to 35) and older adults (over age 50). It is somewhat more common in males than females, and more common in Caucasians than in African-Americans. Because of progress in treating Hodgkin lymphoma, most people with a diagnosis of Hodgkin lymphoma will be long-time survivors.

Non-Hodgkin's Lymphoma classification

Non-Hodgkin's lymphoma can be further classified into a variety of types based on other cell characteristics, such as size, arrangement, growth patterns, and aggressiveness. These characteristics also help your doctor predict the chance that your disease can be cured or put into remission.
Non-Hodgkin's lymphoma is much more common than Hodgkin's disease and is ranked as the fifth most common cause of cancer-related deaths. Your risk of developing non-Hodgkin's lymphoma increases as you get older. You are more likely to get this disease if you are male or white. In addition, its incidence is increasing with each passing decade with the highest number of non-Hodgkin’s lymphoma patients in the U.S.

What is Non-Hodgkin's Lymphoma?

Lymphoma refers to a cancer of the lymphatic system. The lymphatic system is a network of nodes (knots of tissue) connected by vessels. The lymphatic system's largest organ is the spleen. Together, they drain fluid and waste products from all the organs and structures of your body. The lymph nodes act as tiny filters, straining out invading organisms and cancerous cells.
Lymphocytes, a type of white blood cell that attacks infectious invaders, such as bacteria, viruses, and fungi, destroy most infections before they can enter the bloodstream. When the lymphatic system is fighting an active infection, you may notice that some of your lymph nodes and tissue in the area of the infection become swollen and tender. This is normal.
Lymphoma occurs when the lymph-node cells or the lymphocytes begin to multiply uncontrollably, producing cancerous cells that have the abnormal capacity to invade other tissues throughout your body. The two main types of lymphoma are Hodgkin's lymphoma and non-Hodgkin's lymphoma, which are classified by certain unique characteristics of the cancer cells.

The Staging of Hodgkin's Lymphoma

The prognosis and specific treatment used to treat Hodgkin's depends on the stage of the disease or how widespread it is.
Stage I. Hodgkin's lymphoma is found in only one lymph node area or or structure (such as the spleen).
Stage II. Hodgkin's lymphoma is found in two or more lymph node areas on the same side of the diaphragm (the muscle beneath the lungs that moves up and down to help you breathe).
Stage III. Hodgkin's lymphoma is in lymph nodes on both sides of the diaphragm, or the cancer may also have extended to an area or organ adjacent to the lymph node and/or to the spleen.                                                                                                                                                                                                                                               
Stage IV. Hodgkin's lymphoma has spread to one or more organs outside the lymphatic system such as the bone marrow or liver.
Refractory or recurrent Hodgkin's lymphoma. Refractory disease is the term used when the disease progresses or doesn't go into remission while you are still being treated or when you have finished your first treatment step (induction treatment). Recurrent disease means that Hodgkin's lymphoma has come back after it has been treated. This may occur shortly after treatment or years later.