Leukemia, a cancer that originates in the blood and bone marrow, involves an abnormal growth and accumulation of blood cells in the body, including the lymph nodes and spleen. These abnormal cells are unable to fight infection well and can prevent the body from making normal blood cells, which is why patients with leukemia are at high risk for infection and may need frequent infusions of red blood cells and platelets.
According to the American Cancer Society, 60,140 new cases of leukemia are estimated to be diagnosed in the United States in 2016, and more than 316,000 leukemia survivors are living in the United States.
Medical advances in recent years have had a significant impact on the treatment of leukemia with novel drugs and therapies that are approved for newly diagnosed and relapsed leukemia, and some patients with leukemia who continue to take the new drugs can live long and productive lives. Transplant may be the best treatment option and cure for leukemia.
Organizations such as Be The Match have created registries with millions of potential donors who are willing to donate bone marrow.
Leukemia is categorized according to the type of blood cells affected (lymphocytes or myeloblasts) and whether the abnormal cells grow rapidly (acute) or slowly (chronic). There are 4 main types of leukemia:
- Acute lymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Chronic lymphocytic leukemia (CLL)
- Chronic myeloid leukemia (CML)
The risk factors shared by all leukemia types include exposure to high levels of radiation or to certain chemicals. Males are more likely to have leukemia than females.
Genetics and certain inherited conditions are risk factors for ALL and AML. Being white is a risk factor for ALL and CLL. AML and CML occur mostly in people aged 65 or older. Smoking is a confirmed risk factor only for AML. Certain infections are a risk for ALL.
ALL: Acute Lymphocytic Leukemia
ALL is an abnormal growth of immature lymphoblasts (white blood cells) in the bone marrow that replace normal mature white blood cells in the bone marrow and lymph nodes. The ALL cells rapidly multiply and can spread to the lymph nodes, spleen, liver, cerebrospinal fluid, and testicles.
Symptoms. Because abnormal ALL cells replace healthy red blood cells, white blood cells, and platelets, patients may have anemia, shortness of breath, weakness, bleeding and bruising, and an increased risk for infection. Other symptoms include swelling, abdominal pain, fever, night sweats, loss of appetite, and weight loss.
Diagnosis. In addition to a physical exam and medical history, blood tests, and bone marrow and lymph nodes tests are performed to diagnose ALL. A complete blood cell count is used to determine the number of normal cells, flow cytometry is done to determine abnormal cells, genetic tests to look for the presence of genetic mutations (changes), bone marrow aspiration and biopsy to evaluate normal and abnormal cells in the bone marrow, and lumbar puncture to evaluate cerebrospinal fluid for abnormal blood cells. CT scans, MRIs, ultrasounds, and chest x-rays may also be performed to evaluate the severity of the condition.
The treatment of ALL typically involves 3 phases:
- Induction: the use of intense chemotherapy and targeted therapies to kill the leukemia cells
- Consolidation: the use of high-dose chemotherapy and targeted therapies to destroy leftover inactive leukemia cells
- Maintenance: uses lower-dose chemotherapy regimens to prevent new leukemia cells
Radiation therapy can prevent ALL from spreading to the brain. Stem-cell transplant can improve the ability to produce stem cells after receiving very high doses of radiation, chemotherapy, or both.
Drug therapy. The standard treatment for adults with ALL includes chemotherapy drugs, such as vincristine, cyclophosphamide, doxorubicin, and methotrexate. Prednisone may also be given.
Enzyme therapies include Erwinaze (asparaginase) and Oncaspar (pegaspargase).
Antimetabolites are common treatments for ALL.
Blincyto (blinatumomab) is a new immunotherapy for ALL that uses the patient’s immune system to fight cancer.
Targeted therapies for ALL include Gleevec (imatinib), Iclusig (ponatinib), and Sprycel (dasatinib). Immunotherapy is the newest treatment option for ALL.
AML: Acute Myeloid Leukemia
AML is the most common type of acute leukemia in adults. In AML, the bone marrow makes abnormal myeloblasts (certain white blood cells), red blood cells, or platelets. If not treated, AML usually worsens quickly.
Symptoms. The symptoms of AML include fever, shortness of breath, weakness or tiredness, and weight loss or loss of appetite. Patients with AML often bruise and bleed easily.
Diagnosis. AML can be diagnosed with a blood test (complete blood count, peripheral blood smear) and bone marrow biopsy. Other tests may include cytogenetic testing to look for chromosome changes, immunophenotyping to identify the subtype of AML by comparing cancer cells with normal cells of the immune system, and reverse transcription-PCR testing to find changes in genes.
Chemotherapy is a standard treatment for AML and includes cytarabine plus daunorubicin or idarubicin; cladribine may also be added for some patients. Patients who cannot take an anthracycline may receive Fludara (fludarabine) or Hycamtin (topotecan). Other treatments include cyclophosphamide and mitoxantrone.
Patients with AML often also get radiation and stem-cell transplant or bone marrow transplant. Before receiving chemotherapy, a patient may have leukapheresis, when the blood is passed through a machine that removes white blood cells (including the leukemia cells) and returns the rest of the blood to the body.
Targeted drugs are currently being studied in clinical trials for AML.
CLL: Chronic Lymphocytic Leukemia
CLL is a chronic and slow-growing disease. Most patients have too many lymphocytes in the bloodstream, but some have lymphocytes only in the lymph nodes (small lymphocytic lymphoma).
Symptoms. The symptoms of CLL can include fatigue, weakness, weight loss, fever, night sweats, enlarged lymph nodes, and pain or feeling full in the belly as a result of an enlarged spleen and/or liver.
Diagnosis. After a thorough medical exam and complete medical history, doctors can diagnose CLL with a complete blood count or a blood-cell exam (peripheral blood smear). A flow cytometry test, which uses a machine to see if lymphocytes in a blood sample contain CLL cells, is important for the diagnosis. Other diagnostic tests include bone marrow aspiration and biopsy; lymph node biopsy; genetic tests and FISH (testing of chromosomes); and imaging tests, such as CT scan, ultrasound, and MRI.
Chemotherapy for CLL includes fludarabine, chlorambucil, and cyclophosphamide. Before receiving chemotherapy, some patients may have leukapheresis.
New drugs have been approved for CLL in the past decade. New monoclonal antibodies include Arzerra (ofatumumab), Bendeka/Treanda (bendamustine), Campath (alemtuzumab), Gazyva (obinutuzumab), and Rituxan (rituximab).
Targeted therapies include Imbruvica (ibrutinib), Zydelig (idelalisib), and, most recently, Venclexta (venetoclax).
Stem-cell transplant, and less often surgery or radiation, may also be used for CLL.
CML: Chronic Myeloid Leukemia
CML is a slow emerging form of leukemia that affects certain white blood cells. A genetic change resulting in the Philadelphia chromosome causes the bone marrow to make too much of the protein called tyrosine kinase. The tyrosine kinase causes the bone marrow to make too many abnormal white blood cells, leaving less room for healthy white blood cells, red blood cells, and platelets. CML develops in 3 phases—chronic phase, accelerated phase, and blast phase—based on the number of abnormal white blood cells in the blood or bone marrow.
Symptoms. The symptoms of CML develop slowly; in the early phases, most patients don’t have symptoms. With low production of normal blood cells, patients may have anemia, fatigue, weakness, shortness of breath, weight loss, night sweats, fever, bone and joint pain, and an enlarged spleen.
Diagnosis. In addition to blood, bone marrow, and lymph node tests, a cytogenic/karyotyping test (to look for the Philadelphia chromosome) and a molecular test (to look for BCR-ABL gene fusion) can be used to diagnose CML.
The treatment goals in CML are to return the blood counts to normal, reduce or eliminate the number of CML cells in the blood and bone marrow, and preserve quality of life.
The standard treatment of CML includes chemotherapy, targeted drugs, and transplant. Chemotherapy drugs include cyclophosphamide, Synribo (omacetaxine mepesuccinate), and Busulfex (busulfan), and the antimetabolites cytarabine and hydroxyurea.
Treatment with targeted drugs begins with the tyrosine kinase inhibitors (TKIs), which are the first line of treatment for CML. TKIs block the abnormal protein created by the Philadelphia chromosome and regulate normal blood-cell production. Targeted drugs for CML include Bosulif (bosutinib), Iclusig (ponatinib), and, the TKIs Gleevec (imatinib), Sprycel (dasatinib), and Tasigna (nilotinib). Patients may also receive immunotherapy with interferon alfa or stem-cell or bone marrow transplant.
Although stem-cell transplant is the only potential curative treatment option for CML, it is not an option for all patients. Patients with CML who are eligible for transplant may receive allogeneic transplant (which is done after high-dose chemotherapy). The abnormal cells in the bone marrow are replaced with healthy cells from a donor. A second type, reduced-intensity transplant, is when lower-dose chemotherapy and radiation therapy are given to the patient before receiving the donor cells.