Blood cancers

ALSO KNOWN AS: Hematopoietic neoplasms, malignant neoplasms, bone marrow diseases

RELATED CONDITIONS: Leukemia (acute myelogenous or myelocytic leukemia, or AML; acute lymphocytic or lymphoid leukemia, or ALL; chronic myelogenous or myelocytic leukemia, or CML; chronic lymphocytic or lymphoid leukemia, or CLL), lymphoma (Hodgkin disease, or HD; non-Hodgkin lymphoma, or NHL), and myeloma (plasma cell dyscrasia, plasma cell myeloma, multiple myeloma, myelomatosis)

DEFINITION: Blood cancers arise from an abnormality in the production of mature blood cells or their precursor stem cells. Not all bone marrow disorders, such as anemia, are cancers. The three main types of blood cancer are leukemia, lymphoma, and myeloma.

Leukemia is a cancer of any of the five dominant types of white blood cells. It occurs when the bone marrow produces abnormal white blood cells, which then replicate, limiting the ability of healthy cells to function. Chronic leukemia develops slowly, while acute leukemia develops quickly. Of the four subtypes of leukemia, the acute forms exhibit immature blood-forming cells or blasts, while the chronic forms exhibit changes in the presentation of marrow cells but few or no blast cells. Acute lymphocytic leukemia (ALL), also known as acute lymphoid leukemia, is the most common type of blood cancer among those under nineteen years of age. ALL is characterized by lymphoblasts replacing normal cells in the marrow and lymph nodes, lowering the affected individual’s ability to fight infection. Chronic lymphocytic leukemia (CLL) is the most common type of blood cancer among those fifty years of age and older and the most prevalent type of leukemia. Acute myelogenous leukemia (AML), in which leukemic blast cells proliferate and block the production of normal marrow cells, results in a deficiency of red blood cells, white blood cells, and platelets. Chronic myelogenous leukemia (CML) is seen mainly in adults and begins with a change in a single stem cell, a future red or white blood cell, or a platelet.

Lymphomas originate in malignant changes in the lymphatic or immune system. The primary types are Hodgkin disease and non-Hodgkin lymphoma. Hodgkin disease is characterized by abnormal T or B white blood cells. As the abnormal cells divide, they increase and can spread throughout the body. Non-Hodgkin lymphoma is a cancer of the lymphoid tissue, mostly made up of lymph nodes that manufacture and store lymphocytes, white blood cells that protect against infection. Myelomas are progressive blood cancers of plasma cells, which produce antibodies to fight against infections and regulate the immune system. Myeloma results from an overproduction of these antibodies, an impaired immune system, and invasive tumors.

Risk factors: The risk factors and causes of many types of blood cancers are not well known, and most cases occur in individuals with no identifiable risk factors. However, for AML, which along with CLL is among the most common types of blood cancer seen in adults, these specific risk factors have been found: Down syndrome and other genetic disorders, chronic exposure to ionizing radiation and chemicals such as benzene in the workplace, high doses of radiation therapy and chemotherapy to treat lymphoma or other types of cancer, and tobacco smoke. Those who are immunocompromised by certain bacteria or human retroviruses, such as the Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), or human T-cell leukemia virus (HTLV), are at greater risk of developing lymphomas. Familial clustering also has been associated with the development of lymphomas.

Etiology and the disease process: Cancer develops due to various factors over several years. Blood cancers differ widely by group and within each subtype in their progression, causes, and molecular presentation. The leukemias begin in two types of white blood cells: neutrophils and monocytes, which are germ-ingesting cells, and lymphocytes, which are immune-defense cells. Abnormal white blood cells in the bone marrow multiply and enter the bloodstream, crowding out normal cells. Lymphomas develop when these immune-defense cells multiply and cause tumors in the lymph nodes or other parts of the immune system. The development of blood cells through the hematopoietic process is arrested, and abnormal blood cells proliferate. Every stage of hematopoietic development can result in a particular type of cancer. Non-Hodgkin lymphoma (NHL) is manifested by well-differentiated cells with slow progression, while other forms are more aggressive with lymphocytes of limited differentiation. Tumors of the bone marrow are characteristic of myelomas. In myeloma, cells that are to become immune cells develop in the bone marrow from stem cells, as do all blood cells. B lymphocytes, a type of white blood cell typically developing into plasma cells, undergo multiple genetic changes as they change into plasma cells, causing malignant plasma cells to grow. These myeloma cells travel throughout the bloodstream, reside in the bone marrow, and damage healthy tissue. The myeloma interferes with the plasma cell's production of protective proteins called immunoglobulins or antibodies by producing M proteins or abnormal immunoglobulin, making those affected susceptible to infection.

Incidence:

According to the National Cancer Institute, there were about 20,240 new cases of AML in 2023. Overall, the 2021 incidence rate of AML among the general American population is 4.3 per 100,000. Because AML is associated with accumulating genetic defects, the incidence increases with age. In 2021, the AML incidence for those under 15 was 0.7 per 100,000 persons. For those 50-64, the incidence jumped to 5.0. For the ages 65-74, the rate was 14.0. For the population greater than 75, the incidence rate was 27.3. The median age at diagnosis was 68 years old. The median age at death was 74.  

Symptoms: Signs and symptoms of blood cancers vary widely and may be similar to those of other, less severe illnesses. Symptoms vary based on the category and subtype of blood cancer; for example, symptoms of acute leukemia may include pallor, shortness of breath with exertion, lack of energy, night sweats or a mild fever, slow healing of cuts and bruises, unexplained weight loss, tiny red spots under the skin, bone and joint aches and pains, and low white blood cell count (especially neutrophils and monocytes). Although specific bone marrow and blood tests are needed to diagnose any blood cancer, some of those affected with particular subtypes of leukemia may have enlarged lymph nodes in the neck, groin, or armpit, and they may suffer from frequent infections.

Often, individuals who have Hodgkin disease or non-Hodgkin lymphoma experience painless, swollen lymph nodes, loss of appetite, vomiting, bloating, abdominal pain, fullness (due to enlargement of the liver, spleen, or abdominal lymph nodes), pain in the lower back, bone pain, constant coughing, and unexplained lethargy.

Early myeloma symptoms are bone pain, particularly with movement, and infections involving the skin, the urinary tract, the bronchial tract, or lungs. These symptoms may also be accompanied by pallor resulting from anemia, weakness, and exaggerated fatigue.

Screening and diagnosis: Blood tests and specific bone marrow tests are needed to diagnose blood cancer; however, individuals in the early stages of the disease may not have symptoms suggesting cancer. Current evidence does not indicate that routine blood screening before the onset of symptoms will detect cases of blood cancer and lead to improved medical outcomes or be cost-effective in those at average risk of developing cancer according to their medical, family, and occupational history. The first indication that a person has blood cancer may be the results of a blood test performed as part of an annual physical. The blood sample may reveal anemia or changes in white blood cells, a possible indicator of leukemia. If an individual has symptoms that suggest blood cancer, the physician will take a medical history and check for swelling of the liver, spleen, or lymph nodes in the armpits, groin, or neck. Urinalysis will also detect substances or cellular material in the urine. Other tests include:

• A blood test to assess blood cell count.
• A cytogenetic exam to analyze the number and shape of chromosomes for genetic abnormalities and bone marrow aspiration.
• A biopsy to check for cancerous cells in liquid bone marrow or bone specimens.

Additional tests may be ordered if cancerous cells are present to ascertain if the disease has spread to organs or systems. These tests may include tumor marker tests (immunophenotyping, based on the type of antigen or marker on the surface of the cell), a spinal tap or lumbar puncture to obtain a sample of cerebrospinal fluid, chest x-rays to look for signs of infection or lymph-node involvement, or ultrasound scans.

Staging assesses the disease's extent or severity, plans treatment, and predicts the outcome or prognosis. Classification of each type of blood cancer into stages is based on the affected site, the disease's progression, and the affected cells' appearance. For example, CLL is staged according to the risk-based Rai classification system, using symptoms such as blood lymphocyte count, enlarged lymph nodes or organs, platelet count, and anemia. Other forms of leukemia, such as acute leukemia, are not staged because of acute onset, which typically means the cancer has spread to other organs at the time of diagnosis.

Although leukemic cancerous cells circulate in the blood and bone marrow, lymphoma cells form tumors in lymphatic tissue. The Ann Arbor staging system is used for both Hodgkin disease and non-Hodgkin lymphomas based on the specificity of the site of lymph node involvement. The TNM (tumor/lymph node/metastasis) system may be used to stage the size of a tumor, lymph node involvement, and the existence or extent of spread through other parts of the body. The International Staging System (ISS) is used for staging multiple myelomas based on blood tests for two proteins, albumin and beta-microglobulin, which are markers for the disease.

Treatment and therapy: Blood cancers are typically treated with one or more of the following: chemotherapy, radiation therapy, stem-cell transplantation, and immunotherapy. The goal of chemotherapy, drugs given in combination and via different methods of delivery, is to destroy cancerous cells or to stop them from growing and multiplying, producing long-term remission or a cure. Radiation therapy may be used to treat localized cancers such as lymphomas and certain types of leukemia, or it may be used to relieve symptoms when cancerous growths cause pain or pressure on bones, nerves, or organs. However, chemotherapy and radiation therapy can cause long-term or late effects, affecting fertility or growth and causing learning disabilities or illnesses secondary to primary cancer, such as leukemia.

Chemotherapy doses considered tolerable by most patients may not be sufficient to arrest, cause remission in, or cure acute leukemia, myeloma, or lymphoma. In patients who may be at high risk of relapse, who relapse after a successful course of treatment, or who do not respond as expected to conventional therapy, stem cell transplantation can enable the production of normal blood cells such that intensive chemotherapy can bring about recovery. Immunotherapy, using antibodies from the patient or a donor, may be used alone or in combination with other therapies to attack cells that remain after chemotherapy and may attach to antigens on the malignant cells. They also are used as vaccines to suppress malignant cells that remain in the body following therapy.

New chemotherapies, immunotherapies, vaccines, gene therapies, and types of bone marrow transplants to suppress the growth of cancerous cells and affect the course of the disease are constantly being developed and tested. Patients should be reminded that pain and uncomfortable symptoms arising from the toxic effects of cancer treatments can be managed by consulting with their physicians. Supportive care to improve functioning and quality of life, transfusions, antibiotics to protect against infection, and a healthy diet and lifestyle are critical for those undergoing cancer treatment.

Prognosis, prevention, and outcomes: Many factors affect the result of a patient's blood cancer, including the type, location, and stage of disease, as well as individual and demographic factors such as the person's general health, age, and response to treatment. A cancer survivor will undergo follow-up care, which includes frequent monitoring of blood counts, x-rays, urine tests, and imaging tests such as computed tomography (CT) or positron emission tomography (PET) scans. Those whose remission lasts five years are considered cured. Five-year survival rates for those with blood cancer have been rising since 1975 and the advent of more effective cancer treatments.

No specific guidelines for preventing blood cancer exist, as its causes are not known, and many types are relatively rare. Limiting exposure to environmental toxins and leading a healthy lifestyle may help prevent blood cancers in those of average risk. The relative overall five-year survival rate of leukemia for those diagnosed between 2003 and 2009 was 59 percent—nearly double the rate for those diagnosed between 1975 and 1977 (34 percent), according to the LLS. Relative survival rates vary by age at diagnosis, race, gender, and type of leukemia. Of all types of leukemia, those with CLL had the highest relative survival rate during this period, at 83.1 percent.

Hodgkin disease is considered one of the most curable cancers, with many patients cured after their initial treatment. The five-year survival rate has increased substantially since the 1970s, from 72 percent to 88 percent. Similarly, due to advances in the treatment of non-Hodgkin lymphoma, the five-year survival rate increased from 47 percent in the 1970s to 71 percent in those diagnosed between 2003 and 2009. According to the American Cancer Society, by 2023, data indicated that about 90 percent of adults with AML will reach complete remission. Almost 30 percent of adults diagnosed with AML survive three or more years following diagnosis if given aggressive treatment—this is about 67 percent of those who achieve complete remission. For children, the five-year survival rate was 65-70 percent.

In October 2017, the US Food and Drug Administration approved a gene therapy for the treatment of ALL patients who had not responded to previous chemotherapy regimes. Gene therapy is an emerging treatment modality in cancer treatments as it genetically modifies a patient's immune cells to attack cancer. In the 2020s, significant advancements were made in the efficacies of immunotherapies, particularly in eliminating the ability of cancers to escape detection and thus survive and thrive.

Most adults also improve with treatment; the number of adults who have remissions has increased, and the length of adult remissions has improved. According to the National Cancer Institute, in 2022, the rate of new cancer cases had climbed to 1.9 per 100,000 people. Notably, the death rate had fallen to 0.4 per 100,000 people. The overall relative survival rate from cancer was estimated at 72.0 %. The data reflected data collected between 2018 and 2022.

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