Blood and Cancer

Blood and Cancer

Advances in the treatment of blood cancers have led to increasingly high survival rates, and current research continues to offer up exciting progress in the field.

Treatment of blood cancers could be considered a success story. Research uncovering some of the underlying causes of these diseases, combined with increasingly more effective drugs, has resulted in significant strides toward better treatment outcomes during the past few decades. Since 1960 the five-year-survival rate for patients with leukemia has more than tripled; and for patients with lymphoma, the survival rate has doubled, according to the Leukemia & Lymphoma Society. Some blood cancers—such as chronic lymphocytic leukemia and Hodgkin’s lymphoma—now have cure rates that reach 95 percent. That’s the good news. The bad news is that leukemia, lymphoma, and myeloma—the most common types of blood cancers—will still affect an estimated 139,860 people in 2009. And every 10 minutes in the United States, someone dies of a blood cancer.

Overview

Blood cancers form in either the bone marrow or the lymphatic tissues, affecting the way the body makes blood cells and provides immunity from diseases. Bone marrow is the soft, spongy tissue that fills the interior of bones and produces blood cells. Lymph tissue includes the lymph nodes—a network of thin tubes containing white blood cells that are an important part of the immune system and which also act to trap foreign particles. Other lymph tissues include the spleen, thymus, and bone marrow. The three main types of blood cancer involve uncontrolled growth of abnormal cells in the blood and the bone marrow. The accumulation of malignant cells eventually interferes with the body’s production of healthy blood cells.

Lymphoma

Lymphomas, which originate in the lymphatic tissues, result when lymphocytes (a type of white blood cell) undergo changes in their DNA that cause them to multiply continuously, eventually crowding out healthy cells. The lymphoma cells create tumors that enlarge the lymph nodes or grow in lymphatic tissue in organs such as the stomach or intestines. About 53 percent of the blood cancers that occur each year are lymphomas. The two main types of lymphoma are Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL).

Hodgkin’s lymphoma. Hodgkin’s lymphoma was named for Thomas Hodgkin, an English physician who described the disease in the early 1800s. It is one of the most curable types of cancer and is marked by the presence of unusually large malignant cells called Reed Sternberg cells.

Treatment for Hodgkin’s lymphoma involves chemotherapy drugs and radiation aimed at any Hodgkin’s lymphoma tumors or masses. Treatment with chemotherapy may include several drugs, and sometimes as many as four. Chemotherapy kills normal cells as well as cancerous cells, so these medications can have damaging effects on blood cells. Levels of red cells (which carry oxygen in the blood), white cells (which fight infection), or platelets (which are responsible for clotting) may drop. If levels of these cells become very low or if infections develop, patients may need supportive care.

Supportive care might include a red blood cell transfusion or treatment with drugs called blood cell growth factors, which increase the number of neutrophils, a type of white cell, in the blood. When platelet levels drop during treatment, chemotherapy doses might be reduced or the timing between treatments might be extended. In very serious cases, a platelet transfusion may be performed.

In patients who aren’t cured with chemotherapy, another treatment option for Hodgkin’s lymphoma is stem cell transplantation. A transplant of the patient’s own blood-forming stem cells (called an autologous stem cell transplantation) allows treatment with high doses of chemotherapy, radiation, or both. In some cases, patients undergo an allogeneic transplant, in which blood stem cells from another person—usually a relative or someone with matching tissue types—are used. Before receiving high-dose treatment, the stem cells are removed and may be treated to remove any lymphoma cells. After high-dose treatment, the stored stem cells are returned to the patient, allowing new blood cells to develop.

Oliver Press, MD, PhD, professor of medicine at the University of Washington and past chairman of the Lymphoma Research Foundation Advisory Board, says, “Transplants often work best when the disease is not totally resistant to chemotherapy, when the patient is in good physical shape, or when the size of the tumor burden is small.” Elderly patients are often not candidates for stem cell transplants because of the risks involved, which are serious and can include death.

Non-Hodgkin’s lymphoma. By contrast, non-Hodgkin’s lymphoma begins when a lymphocyte, usually a B-cell, becomes abnormal. There are more than 60 types of NHL. “They can be broadly divided into indolent lymphomas and aggressive types,” says Michael Williams, MD, chief of the hematology section and director of the hematologic malignancy program at the University of Virginia School of Medicine. Indolent NHL cancers are often slow growing, Dr. Williams says, and patients can typically live with them for many years, even without treatment. “Yet they’re not curable with standard treatments,” he adds, “and patients are often required to go on and off treatments for years to keep the disease under control.”

Aggressive NHL, on the other hand, can be cured with chemotherapy or chemotherapy combined with Rituxan® (rituximab), a targeted monoclonal antibody, which is a therapy that’s been in use for about 10 years.

Problems arise, Dr. Williams says, when patients show resistance to treatment or if they relapse, in which case, “survival can be less than a year unless further effective treatment is given.” Patients with relapsed NHL can benefit from higher-dose chemotherapy and autologous stem cell transplants, however, which can improve survival and lead to cure in some cases.

Rituxan—which helps destroy B-cell lymphoma cells by targeting a protein present on most cells—has been one of the most helpful advances in NHL treatment in recent years. Rituxan is a monoclonal antibody, a group of drugs that contain manufactured antibodies—specialized proteins produced by the immune system—that hone in like guided missiles to attack cancer cells.

Treatment with Rituxan does not result in the same side effects as those associated with traditional chemotherapies, such as hair loss, nausea, or increased risk of infection. “It’s one of the safest of the lymphoma drugs, which has made it popular with both patients and doctors,” Dr. Press says. By combining Rituxan with other drugs, he adds, the drugs’ cancer-killing power is increased, with very little increase in toxicity.

“Quality of life is often very good for patients with indolent lymphoma treated with Rituxan alone,” says Dr. Williams, “and treatment is usually completed in a period of several weeks rather than several months as with chemotherapy.”

Clinical scientists are now testing other targeted therapies similar to Rituxan that attack NHL, including B-cell lymphomas. “There are probably 20 new antibodies being developed to improve on Rituxan,” says Dr. Press. “The next decade will be very exciting as we determine which of these will be the most effective in NHL.”

Leukemia

Leukemia is another common blood cancer and is one of the 15 most frequently occurring cancers, according to the Leukemia & Lymphoma Society. An estimated 44,790 new cases of leukemia will be diagnosed in 2009. Leukemia starts in the bone marrow and causes production of abnormal white blood cells that keep replicating. These abnormal cells may crowd out normal white blood cells, red blood cells, and platelets, making it difficult for them to do their work.

Leukemia that starts in the bone marrow’s lymphoid cells, which usually form white blood cells known as lymphocytes, is known as lymphocytic leukemia. The disease can also start in a myeloid cell, a type of bone marrow cell that goes on to form red blood cells, some types of white cells, and platelets. These types of leukemia are known as myelogenous. Both lymphocytic and myelogenous leukemia can be either acute or chronic. Chronic leukemias usually get worse slowly, and people may not have any symptoms at first. The leukemic cells may be able to perform some of the functions of normal white blood cells at first, but in acute leukemias the abnormal cancerous cells can’t do any of the work of normal white blood cells. The number of leukemic cells increases rapidly, and the disease can worsen very quickly. People with acute leukemias usually need prompt treatment, and symptoms include infections, aches in the bones or joints, and low white blood cell counts.

The type of treatment varies with each type of leukemia as well as with the patient’s age and general overall health. Patients with acute leukemias usually begin treatment with chemotherapy; and even after the disease is in remission, they may continue to receive chemotherapy, perhaps for several years. Sometimes allogeneic stem cell transplantation is used along with these drugs. Treatments for acute leukemias rely on drugs that have been used successfully since the 1950s to cure and extend survival for the majority of patients. Treatments for childhood leukemias have been especially successful, and 90 percent of children with acute leukemias live five years or more with the disease, according to Barton Kamen, MD, PhD, executive vice president and chief medical officer of the Leukemia & Lymphoma Society. “The drugs we use in acute leukemias are not brand-new, but we’ve learned how to use them better,” he says. “We also have much better supportive care. But there are no magic bullets in acute leukemias.”

By contrast, targeted therapies, including monoclonal antibodies such as Rituxan, are used for patients with chronic leukemias. One of the success stories among targeted therapies is Gleevec® (imatinib mesylate), which can help keep chronic myeloid leukemia (CML) under control for long periods. This drug as well as other new targeted therapies such as Sprycel® (dasatinib) and Tasigna® (nilotinib) block the BCR-ABL cancer gene that helps cause CML. “In a matter of a decade, Gleevec has taken the survival rate in CML from 50 to 95 percent at 10 years,” said Dr. Kamen. “This drug has meant that most patients with CML will live 10 years if not 15 years, although it’s not necessarily a cure,” he added. The only treatment that can cure CML is allogeneic stem cell transplantation.

Multiple Myeloma

After lymphoma and leukemia, the third most common type of blood cancer is multiple myeloma. Myeloma starts in the plasma cells, which make up the fluid in which blood cells are suspended. Abnormal plasma cells start to increase, especially in the bone marrow, and eventually disrupt normal blood cell production. Plasma cells normally make proteins called immunoglobulins, which are an important part of the body’s immune system. Myeloma cells interfere with this production and also make abnormal immunoglobulin called M proteins that don’t protect the body against infection.

As multiple myeloma tumors grow, they invade the bone’s solid tissue and form multiple small lesions. Plasma cells sometimes collect within bone and soft tissue—a phenomenon known as plasmacytomas—and these growths generally signal a more aggressive type of myeloma. Bone pain is often the first symptom of myeloma. Fractures can also occur from weakened bones; other signs and symptoms are anemia and recurrent infections.

Although multiple myeloma is considered incurable, there has been remarkable progress in the treatment of the disease. In the past five to 10 years, four new drugs have been approved by the U.S. Food and Drug Administration—Thalomid® (thalidomide), Revlimid®(lenalidomide), Velcade® (bortezomib), and Doxil® (pegylated liposomal doxorubicin)—that have extended the lifespan of myeloma patients from an average of 3 to 4 years to 7 or 8 years, according to Ken Anderson, MD, Kraft Family professor of medicine at Harvard Medical School and the Dana Farber Cancer Institute.

Myeloma can be “smoldering” (slowly progressive) or active with significant symptoms. Most newly diagnosed patients with active disease receive high-dose chemotherapy, often including some of the new drugs now available, or a stem cell transplant, depending on their age and physical condition. Even those who are not eligible for stem cell transplants—because of their age or physical condition—can go on to treatment with the new drugs now available. Side effects of these drugs include neuropathy, or pain and numbness in the nerves, especially the hands and the feet. This symptom can be alleviated by reducing the drug dosage or changing the administration schedule. Lowered platelet counts can also result, which can be managed by changing the dosage and the schedule of treatments, or in some cases, with transfusions. “In general, the side effects of these drugs are quite manageable,” says Dr. Anderson.

“A very exciting area in myeloma treatment is the use of combination treatments—combinations of drugs that can overcome resistance to prior treatments,” Dr. Anderson says. By combining the power of these drugs, they can kill more cancer cells, and can overcome resistance to previous treatments. “Because we’re using several drugs for treatment,” he adds, “we can also use lower dosages. And that means fewer side effects for patients.”

“There are a lot of changing paradigms in myeloma because of the new drugs that are available to us now,” says Todd Zimmerman, MD, hematologist and associate professor of medicine at the University of Chicago. “There are also all sorts of new targeted therapies that are under development. It’s a very exhilarating time for research in myeloma—research that will eventually extend patients’ lives.”

Can Solid Tumors Affect the Blood?

The answer may be more complex than you think. In rare instances, metastatic solid tumors can have detrimental effects on the blood. Conventional chemotherapy treatments for solid tumors can also affect the blood and the ability of blood cells to protect against infection.

Sometimes, when solid tumors metastasize to the bone marrow (the spongy tissue inside bones), blood cells may be affected. The bone marrow—which produces blood cells—cannot function properly. The result can be three different conditions that affect the blood, called neutropenia, thrombocytopenia, and anemia. Neutropenia results from low levels of white blood cells called neutrophils, which protect against bacteria and fungi by engulfing them like Pac-Man. Thrombocytopenia is a condition in which there are low levels of blood platelets, which help the blood to clot. Anemia results from low levels of red blood cells, which carry oxygen to the organs.

Some solid tumors called adenocarcinomas, or tumors of glandular tissues, can also deposit a gelatin-like material called mucin in blood vessels. This material can collect, forming clots, which causes red cells to be damaged or destroyed as they travel through the blood vessels.

Chemotherapy for solid tumors can also affect the ability of the bone marrow to function, lowering production of neutrophils, platelets, or red blood cells.

The potential danger of a low neutrophil count is a decreased ability to protect against bacterial and fungal infections. “As opposed to what many people think, the danger is not infections from the environment but infections from bacteria that live in our own guts and skin,” says Hector Preti, MD, medical oncologist and medical director for the oncology unit at Methodist Hospital in Houston and clinical associate professor at Baylor College of Medicine. The reason why many patients who receive chemotherapy are told to avoid people with the cold and flu, however, is that colds can be hard to distinguish from bacterial infections, and flus can lead to bacterial infections, sometimes life-threatening ones.

Thankfully, there are treatments called white blood growth factors that can help the body make more neutrophils or other white blood cells. Neutropenia can also be treated by lowering the dosage of chemotherapy or increasing the time between treatments, as can other conditions involving low blood cell counts.

If chemotherapy causes low platelet counts, the danger is spontaneous bleeding, although this type of complication is rare. “You can have very low levels of platelets and still not have significant risk of bleeding,” says Dean W. Felsher, MD, PhD, associate professor in the Division of Oncology at Stanford University. If the platelet counts do get very low, however, patients can be given transfusions, he added.

Anemia, or low red blood cell counts from chemotherapy, can cause fatigue that seriously affects a patient’s quality of life. If chemotherapy causes anemia symptoms, the treatment is usually a transfusion of red blood cells or treatment with drugs called erythropoiesis-stimulating agents. These medicines tell the bone marrow to make more red blood cells. If the patient is deficient in iron, folic acid, or vitamin B12, taking supplements can help anemia, as may eating foods high in iron, according to the American Society of Clinical Oncology.

Be Proactive

Patients benefit from being fully informed about the role that a stem cell transplantation might play in their overall treatment plan.

Stem cell transplants can play a role in the management of most blood cancers as part of first-line treatment, as treatment for patients whose cancers have relapsed, and for those patients who didn’t respond to initial treatment. Stem cell transplants have been clinically proven to improve the outcomes of selected patients with non-Hodgkin’s lymphoma, Hodgkin’s disease, all leukemias, multiple myeloma, and myelodysplastic syndromes.

The reason why stem cell transplants can improve outcome in blood cancers is because the procedure allows for the delivery of high doses of chemotherapy and radiotherapy. Remission and cure rates for leukemia, lymphoma, and myeloma increase with higher doses of chemotherapy and/or radiotherapy. Without stem cell transplants, the ability of the bone marrow to make normal blood cells after very high doses of treatment is impaired, resulting in the patient’s succumbing to infection or hemorrhage from loss of white blood cells or platelets. With the infusion of stem cells from a closely matched donor or one’s own treated stem cells, blood marrow function can recover from intensive treatment.

The success of stem cell transplants often varies depending on the patient’s age, medical condition, and likelihood of response to treatment as well as the availability or necessity of a stem cell. Patients with blood cancers should identify the cancer center most appropriate for their specific diagnosis and should consider seeking a second opinion at a stem cell transplant center to best understand the role that stem cell transplantation may play in the optimal management of their diagnosis.

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