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Leukemia, Hodgkin and non-Hodgkin lymphoma, myeloma and myelodysplastic syndromes are cancers that originate in the bone marrow or lymphatic tissues. They are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. The accumulation of malignant cells interferes with the body's production of healthy blood cells.
New Cases
An estimated 138,530 people in the United States will be diagnosed with leukemia, lymphoma or myeloma in 2008. New cases of leukemia, Hodgkin and non-Hodgkin lymphoma and myeloma account for 9.6 percent of the 1,437,180* new cancer cases diagnosed in the United States this year.
*Source: Surveillance, Epidemiology and End Results (SEER) Program 1975-2005, National Cancer Institute, 2008.
Deaths
Leukemia, lymphoma and myeloma will cause the deaths of an estimated 52,910 people in the United States this year. These blood cancers will account for nearly 9.4 percent of the deaths from cancer in 2008 based on the 565,650 total cancer-related deaths.
Every ten minutes, another child or adult is expected to die from leukemia, lymphoma or myeloma. This statistic represents nearly 145 people each day, or six people every hour.
Leukemia causes more deaths than any other cancer among children and young adults under the age of 20.
Treatment
Drug and Radiation Therapy. The dramatic improvement in managing blood cancers is mainly the result of chemotherapy (anticancer drugs), usually in combinations of two or more drugs. Approximately 50 different chemotherapeutic agents are now used to treat patients with leukemia, lymphoma and myeloma. Patients with high-risk subtypes of myelodysplastic syndromes are also treated with chemotherapy.
Patients with acute leukemia, some types of Hodgkin and non-Hodgkin lymphoma or myeloma with disease that is amenable to radiation therapy may receive both primary chemotherapy and ancillary radiation therapy or radiation therapy alone.
Blood and Marrow Stem Cell Transplantation. Cancer treatment with high-dose chemotherapy or radiation therapy may result in severe injury to blood-forming cells in marrow. Stem cell transplantation was introduced approximately 50 years ago and is now standard therapy for selected patients with leukemia, lymphoma, myeloma and myelodysplastic syndromes.
Types of stem cell transplants. Syngeneic transplantation involves the use of donor stem cells from the blood or marrow of an identical twin. Allogeneic transplantation involves the use of donor blood or marrow stem cells, either from a sibling with the same tissue type or, if a "matched" related donor is not available, from a matched-unrelated donor found through a search of the National Marrow Donor Program registry of tissue-typed volunteers. The chance of having a full match with a sibling donor is about 25 percent. The efforts of the National Marrow Donor Program and other donor registries have created a bank of about 7 million potential donors. As a result, the chance of having a donor can be as high as 80 percent for some population groups.
Umbilical cord blood, like marrow and blood, is a rich source of stem cells for allogeneic transplantation, especially for children and smaller adults. To date, there have been more than 5,500 cord blood stem cell transplants from unrelated donors and several hundred from sibling donors worldwide for patients (mostly children) with some 70 diseases, including leukemia, lymphoma and myelodysplastic syndromes. In special instances, slightly mismatched cord stem cell donors may be used quite successfully, especially in young children.
The numbers of stem cells in cord blood are often insufficient for the needs of larger adult patients. Clinical trials of transplantation with two cord blood units (double cord blood transplant) have shown promising results with more rapid engraftment than that seen with single-unit transplants and improved survival.
Research is being conducted to improve the so-called "haploidentical" transplant, for which a parent rather than a sibling could be the donor. Such an approach would greatly lessen the proportion of children without a suitable donor.
Autologous transplantation is an important therapy that uses the patient's own stem cells. Technically this therapy is "stem cell infusion" and not transplantation since there is no donor involved. The patient's blood or marrow stem cells are collected while he or she is in remission. The stem cells are frozen and then thawed and infused into the patient if intensive chemotherapy and/or radiotherapy is required for subsequent treatment.
"Reduced-intensity allogeneic stem cell transplantation," also called "nonmyeloablative" allogeneic stem cell transplantation is the term for an allogeneic transplant that uses lower doses of chemotherapy and/or radiotherapy to prepare the recipient to receive the donor's stem cells. This experimental approach decreases the toxicity associated with the pre-transplant conditioning therapy needed for a standard allogeneic stem cell transplant. Reduced-intensity transplants depend on the use of immunosuppressive drugs to prevent rejection of the graft so that donor immune cells can engraft and combat the cancer cells. The effectiveness of reduced-intensity transplantation is due to the graft-versus-host disease effect of the donor's lymphocytes on the cancer cells rather than to the high doses of pre-conditioning therapy used for standard allogeneic transplantation. If the results of ongoing clinical trials prove effective, this therapy will extend the upper age range of patient's who can benefit from an allogeneic transplant.
Quality of Life. Improvements in treatment continue to increase survival for many patients diagnosed with blood cancers. In addition, research has identified other ways of improving the quality of care and the health of patients with blood cancers. Psychosocial problems created or made worse by a blood cancer diagnosis, such as depression, anxiety, lack of information or skills needed to manage illness, lack of transportation or other resources and disruptions in work or school, can cause added suffering and interfere with treatment. The Institute of Medicine's (IOM) report Cancer Care for the Whole Patient—Meeting Psychosocial Health Needs (October 2007), identifies approaches that all cancer-care providers, including those with the fewest resources, can use to meet the need for services to address psychosocial needs. The IOM report recommends that the National Cancer Institute, the Centers for Medicare and Medicaid Services and all other organizations that set standards for cancer care incorporate psychosocial health into their standard of care and into research topics, policies, protocols and standards.
Survivorship
An estimated 894,543 Americans are currently living with leukemia, Hodgkin and non-Hodgkin lymphoma, myeloma and myelodysplastic syndromes.
Regular medical follow-up enables doctors to assess the full effect of therapy, detects recurrence of the disease and identifies long-term or late effects. Cancer survivors should see their primary-care physicians for general health examinations and an oncologist for follow-up care related to cancer. Coordination between specialists and primary care physicians is essential to provide the best care.
Follow-Up Guidelines for Survivors. Several organizations are working on evidence-based guidelines for adult blood cancer patients and their physicians that will standardize follow-up care and increase awareness about long-term and late effects.
Some treatment centers have follow-up clinics that provide a comprehensive, multi-disciplinary approach to monitoring and supporting cancer survivors. Most follow-up clinics specialize in pediatric cancer survivors, but some follow adult cancer survivors. Cancer survivors should have physical examinations yearly or more often, as needed. Regular examinations may include screening for cancer recurrence or the development of secondary cancer or other late effects of treatment.
Click here for the Children's Oncology Group's list of Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers.
Click here for a list of NCI-designated Comprehensive Cancer Centers that are members of the LIVESTRONG Survivorship Center of Excellence Network:
New Approaches to Treatment
Several areas of research have resulted in new approaches to the treatment of leukemia, lymphoma, myeloma and myelodysplastic syndromes. For patients with chronic myelogenous leukemia (CML), Philadelphia-positive acute lymphocytic leukemia (ALL), lymphoma, myeloma and myelodysplastic syndromes advances have come from novel agents used alone or in combination with chemotherapy.
Risk-Adapted Therapy. Research is under way to identify biomarkers that give physicians information about the type and amount of therapy needed by different patients who have the same broad diagnosis. Biomarkers may also be able to indicate which patients have a higher-than-normal risk of developing a specific long-term or late effect.
Biomarkers could be high levels of certain substances in the body such as antibodies or hormones, or genetic factors that can increase susceptibility to certain effects. Identifying these biomarkers will allow researchers to develop tests that can predict what effects an individual is at risk of developing, thereby allowing doctors to plan treatment accordingly.
Drugs. In the past decade, several important new drugs and new uses for existing drugs have greatly improved cure rates or remission duration for many patients. Imatinib mesylate (Gleevec®) is now the drug of choice in newly diagnosed patients with CML. Gleevec blocks the oncogene-encoded protein product that allows for the development of the leukemic cell. Gleevec offers several significant advantages to patients: oral administration, decreased side effects and a very high response rate. The effectiveness of the drug, its tolerance by older patients and the projections from the first six years of clinical trials in newly diagnosed patients indicate that Gleevec prolongs the duration of remission and life when compared to former therapy. A minority of patients do not respond to or tolerate this drug or have developed resistance to it. However, two second-generation agents (called "tyrosine kinase inhibitors"), dasatinib (Sprycel®) and nilotinib (Tasigna®), are now approved by the U.S. Food and Drug Administration (FDA). These agents can produce an excellent response in many cases. Trials are under way to determine if one of these second-generation drugs should become the drug of choice to initiate therapy for some or all patients and if the combined use of two drugs would be better than one.
Gleevec and other tyrosine kinase inhibitors are not only important new agents in the treatment of CML, but they also can also induce remissions in some cases of Philadelphia-positive ALL, chronic eosinophilic leukemia, chronic myelomonocytic leukemia and systemic mastocytosis because patients with these conditions have a related genetic abnormality.
Lenalidomide (Revlimid®), a thalidomide derivative, has been approved by the FDA for the treatment of a specific subtype of myelodysplastic syndromes that results from a deletion of part of chromosome 5. In patients with anemia, principally, but without this specific chromosome 5 abnormality, about 20 percent of cases also derive benefit. Patients with more severe forms of myelodysplastic syndromes are unlikely to respond to this agent. Azacitidine (Vidaza®), and decitabine (Dacogen®), approved by the FDA for all types of myelodysplastic syndromes, kill unhealthy marrow cells and may help the marrow function more normally, reducing the need for transfusions in some patients.
Clofarabine (Clolar®), approved by the FDA to treat relapsed or refractory ALL in children who have received at least two prior therapies, is being studied in clinical trials to treat adult acute leukemia and myelodysplastic syndromes. Other therapies in clinical research to treat myelodysplastic syndromes include arsenic trixoxide, valproic acid (Depakene®), a drug approved to treat certain seizure disorders, and vorinostat (Zolinza®), an agent this is approved to treat cutaneous lymphoma.
The remission rate and duration of remission of acute promyelocytic leukemia (APL)has been improved significantly with the introduction of all-trans retinoic acid (ATRA) in combination with chemotherapy (anthracycline antibiotic). Arsenic trioxide also adds to the drugs available to treat this subtype of acute leukemia. Arsenic trioxide (Trisenox®) is approved by the FDA to treat patients who have relapsed or are resistant to treatment with chemotherapy and ATRA. The combination of arsenic trioxide and all-trans retinoic acid may be a further advance in the initiation of therapy.
Successful treatment of hairy cell leukemia, a type of chronic lymphocytic leukemia (CLL), has increased with the use of cladribine, which induces long-term remissions in nearly 90 percent of patients treated at diagnosis for one week. Pentostatin is another effective drug that can be used in patients with hairy cell leukemia who do not respond to cladribine.
Several newer therapies have created more treatment options for patients with myeloma. Thalidomide (Thalomid®), in combination with dexamethasone, is approved by the FDA for newly diagnosed myeloma. Bortezomib (Velcade®) is approved by the FDA to treat people with previously untreated myeloma and to treat patients with myeloma and mantle-cell lymphoma who have had at least one prior therapy. The 2007 FDA approval of Velcade and doxil (a chemotherapeutic agent) combination therapy offers another important new option for treating relapsed or refractory multiple myeloma. Revlimid is approved by the FDA in combination with dexamethasone for the treatment of myeloma patients who have received at least one prior therapy. The use of the newer drugs in various combinations and with chemotherapy are being studied in clinical trials.
Bendamustine (Treanda®), an intravenously administered chemotherapy agent, was approved in March 2008 to treat CLL and is showing promising results in clinical trials to treat follicular NHL that does not respond to rituximab (Rituxan®), either as a single agent or in combination with chemotherapy.
Immunotherapy. This is a treatment that uses immune cells or antibodies to fight disease. Immunotherapies suppress disease progression and enhance the specificity of treatment to minimize toxic effects on normal tissues. Three types of immunotherapy are being explored: antibody treatment, vaccine development, and immune cell administration.
Monoclonal Antibody Therapy. Monoclonal antibodies are laboratory-produced proteins that can be infused into patients when indicated for the treatment of patients with certain blood cancers. These agents target antigens on the surface of cancer cells. The antigens are described by a "cluster designation" (CD) followed by a number, for example CD20.
Rituximab is an important antibody that targets the CD20 antigen on B cells (B lymphocytes). Initially Rituxan was used to treat indolent (slow-growing) lymphomas, such as follicular lymphoma. It is also approved to treat aggressive lymphomas (such as diffuse large B-cell lymphoma) in combination with chemotherapy. Rituximab is also used in combination with chemotherapy to treat some patients with CLL and myeloma. Alemtuzumab (Campath®) is a monoclonal antibody directed against the antigen CD52 found on T and B lymphocytes. It is especially active against the lymphocytes in CLL; in 2007, the FDA expanded labeling and granted regular approval for single-agent Campath for the treatment of CLL.
Another antibody that has been approved for use by the FDA to treat certain patients with AML is linked to a chemical toxin called calicheamicin. This drug, gemtuzumab (Mylotarg®), is approved for older patients with AML who relapse after initial treatment. This agent is also being studied in clinical trials in combination with other drugs to treat children with relapsed AML.
Monoclonal antibodies can also be linked to a radioactive isotope to target and kill specific cancer cells. These antibodies are injected into the patient in the hope that the antibodies will latch onto the antigen on the cancer cells and destroy the cells. These are called conjugated monoclonal antibodies. They deliver the toxic substance directly to the cancer cells. Examples of this treatment are the drugs ibritumomab (Zevalin®) and tositumomab and iodine I131 tositumomab (Bexxar®). These drugs have been approved to treat relapsed B-cell NHL.
Many potentially effective new monoclonal antibodies are being studied in clinical trials for several types of blood cancer.
Donor Lymphocyte Infusion. This type of therapy makes use of donor lymphocytes that are given to a patient who has already received a stem cell transplant from the same donor. In patients with CML who have relapsed after stem cell transplantation, the infusion of the original marrow donor's lymphocytes can re-induce remission. Patients with myeloma also have had remission re-induced by donor lymphocytes. This type of treatment is being studied intensively to learn more about the basis for this immune cell effect and to expand it for use in other types of blood cancer.
Vaccines. Experimental vaccines are being studied to treat certain types of lymphoma, myeloma and leukemia. The goal is to extend the duration of remission achieved by remission-induction therapy of various types. These types of vaccines would be used in patients who have small amounts of residual blood cancer after chemotherapy or stem cell transplantation.
Many cancer treatment vaccines under development are intended to induce antigen-specific antitumor immune responses. This means that the vaccine induces an immune response against the cancer cells present in the patient. Some vaccines contain antigens or parts of antigens purified from cancer cells obtained from the patient or from the same type of cancer cells but obtained from another patient. The results of vaccine studies for patients with follicular lymphoma demonstrate that the vaccines can produce an immune response in certain patients.
Multidrug Resistance. Cancer cells have mechanisms that sometimes allow them to escape the damaging effects of chemotherapy agents. These cells are, or become, less responsive to chemotherapy. Approaches to addressing multidrug resistance are under study. The goal of several new agents being studied is to decrease resistance to an important chemotherapy drug used in leukemia. These agents are currently being tested in patients with AML and myeloma in the hope that they may decrease drug resistance and increase the rate of a prolonged response to therapy. Another approach is to use agents that kill cells resistant to standard chemotherapeutic agents. This approach is being studied in CLL patients with deletions of part of chromosome 17, a mutation that increases resistance to standard treatment.
Gene Therapy. One approach to this type of treatment is to use "antisense" agents that block the encoding instructions of an oncogene so that it cannot direct the formation of the corresponding oncoprotein that causes the cell to transform into a malignant cell. These agents can act on the gene (DNA) or on RNA to prevent the formation of the gene product or protein (oncoprotein) that is the direct cause of transforming the cell into a malignant type.
In another approach, drugs are designed to interfere with the oncoprotein and prevent its effect on the cell.
In studies of CML, gene therapy researchers are trying to modify an oncogene (BCR-ABL) that produces a protein that stimulates malignant cell growth. An alternative strategy called molecular-targeted drug development targets the oncoprotein. Two new and potentially important approaches include a) the application of RNA interference; b) a modality that uses molecules of RNA to silence complementary (DNA) genes; and c) aptamer treatment, a technique that prepares small molecules in the laboratory that have the ability to inactivate proteins that cause disease. If the gene in the former case is an oncogene or the protein in the latter case is an oncoprotein, new forms of cancer therapy may be developed.
Statistics are from The Leukemia & Lymphoma Society's Facts 2008-2009.