Leukemias are malignancies of hematopoietic and lymphoid tissues. About 60,000 new cases are diagnosed in the United States each year. There are many varieties of leukemia, and they can be distinguished by the affected tissue type. Myeloid neoplasms include acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Lymphocytic neoplasms include acute lymphoid leukemia (ALL) and chronic lymphoid leukemia (CLL).
Myeloid leukemias are derived from bone marrow progenitor cells. These cells normally develop into to granulocytes, erythrocytes, and megakaryocytes.
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults, accounting for about 80% of all cases. The median age at diagnosis is 65. Patients usually present with signs and symptoms related to pancytopenia, such as fatigue, increased risk for infections, and bleeding complications.
Chronic myeloid leukemia (CML) is characterized by uncontrolled production of neutrophils, eosinophils, and basophils. It accounts for about 15%-20% of leukemias in adults. As with AML, its median age at diagnosis is 65. CML is identified by a typical translocation, called the Philadelphia chromosome, which results in a fusion protein (BCR-ABL) that releases controls on stem cell proliferation and blocks apoptosis.
CML can have several stages in its clinical course: a chronic stage, an accelerated stage, and a blast crisis.
Clinical symptoms of CML are generally nonspecific. Common presentations include fatigue, weight loss, left upper quadrant pain with splenomegaly, and abnormal bleeding. Anemia, leukocytosis, and thrombocytosis may also be found. Many patients with chronic leukemia remain asymptomatic, with discovery of the disease occurring during routine blood tests.
Acute lymphoid leukemia (ALL) is a proliferation of lymphoid precursors, primarily of B-cell origin. ALL accounts for about 12% of all leukemias in the United States but represents 60% of leukemias in persons younger than 20 years.
Bone pain and lymphadenopathy are common findings on presentation of ALL. A mediastinal mass may also be present. Blood abnormalities may include anemia, thrombocytopenia, and the presence of lymphoblasts on peripheral smear.
Chronic lymphoid leukemia (CLL) is a malignancy of mature B cells. It is the most common adult leukemia, with more than 80% of cases occurring in patients over the age of 60. Worldwide incidence is highly variable; North America has the highest rate, while CLL is rare in Southeast Asia.
Most patients are asymptomatic upon presentation with CLL and are found to have the disease due to elevated lymphocyte counts on laboratory tests. Sometimes patients are found to have lymphadenopathy, splenomegaly, and/or hepatomegaly.
Age: ALL occurs mostly in children, with a peak age range of 3-5 years. AML incidence increases with age, peaking at about age 60. CLL and CML are also both diseases of adults, with onset most common in patients older than 50.
Sex: ALL, AML, and CLL are more common in males.
Race/ethnicity: AML is more common in white populations, and CLL is more common in Eastern European Jews.
Genetic abnormalities: AML has been associated with genetic abnormalities such as trisomy 21, Fanconi’s anemia, and Bloom’s syndrome. Children with Down syndrome are at increased risk for both AML and ALL.
Viral exposure: Exposure to human T-cell lymphoma/leukemia virus (HTLV-1) and Epstein-Barr virus may increase the risk of some ALL subtypes.
Radiation exposure: Ionizing radiation is associated with increased risk for AML and ALL, and is the only known risk factor for CML.
Tobacco: For AML, tobacco use is a strong risk factor, accounting for about 1 in 5 cases.
Chemicals: Exposure to benzene, petroleum products, and pesticides is associated with increased risk for AML. Prior chemotherapy is also a risk factor and accounts for up to 10% of AML cases. Some studies suggest that herbicides (including Agent Orange) and insecticides may increase risk for CLL.
Family history: For CLL, risk is increased in first-degree relatives of affected patients.
Complete blood count with white blood cell (WBC) differential can give a presumptive diagnosis. For acute leukemias, the WBC count is usually above 15,000 (and may exceed 100,000), with blast cells usually evident. However, a significant minority of patients will present with a decreased WBC count. Anemia and thrombocytopenia are usually present. Auer rods (azurophilic, rod-shaped inclusions in the cytoplasm of blasts) are almost diagnostic for AML.
The classic diagnosis for CLL requires an absolute lymphocyte count higher than 5,000 without another known cause for the lymphocytosis. Anemia or thrombocytopenia at presentation is correlated with a more aggressive clinical course.
In CML, the peripheral blood shows an increased WBC count with a significant left shift that includes cells usually seen only in the bone marrow. An increased number of basophils is almost always seen and can substantially predate an increase in WBCs. Thrombocytosis occurs in at least half of cases at presentation.
Bone marrow biopsy is often necessary for definitive diagnosis and staging. For CLL and CML, flow cytometry on peripheral blood can be diagnostic. For CML, polymerase chain reaction (PCR) on peripheral blood can demonstrate the presence of the Philadelphia chromosome.
AML is usually treated with chemotherapy, the goal being complete remission and cure of the disease. Allogeneic stem cell transplant can be used in younger patients.
With intensive chemotherapy regimens, about 80% of children and 40% of adults with ALL will be cured.
The treatment of CML is partly determined by the phase at presentation. Imatinib, a tyrosine kinase inhibitor, is currently the treatment of choice at diagnosis for patients in the chronic phase of CML. Allogeneic stem cell transplant is appropriate (except in elderly patients) when imatinib cannot sustain a complete remission. Standard chemotherapy is currently used only in palliative efforts after progression.
Many patients with CLL can be observed without immediate treatment (up to one-third never require treatment). When initiated, treatment consists of chemotherapy and/or monoclonal antibody therapy. Allogeneic bone marrow transplantation is a potentially curative treatment for CLL in younger patients, but it is not yet considered standard therapy. Radiation therapy may be indicated for palliation in patients with large, bulky masses that cause compression symptoms.
The body of scientific literature addressing the role of diet in leukemia risk is considerably smaller than for solid tumors. Epidemiologic evidence suggests that the following factors are associated with reduced risk, although all require further study.
Diabetic pregnancy and maternal obesity. Women with diabetes prior to pregnancy were shown to have a 37% greater risk for having a child who developed leukemia, and those with a BMI between 25 and 30 had a 27% greater risk.
In the NIH-AARP cohort study, individuals who ate the most meat had a 45% greater risk for AML, compared with those who ate the least. Evidence of an effect of eating cured meats on childhood leukemia is sparse; however, the most recent case-control study indicated a nearly 75% greater risk in Chinese children who ate these foods more than once per week compared with those consuming them rarely or occasionally. Previous studies of children found that those eating more than 12 hot dogs per month had 9 times the usual risk of developing childhood leukemia. Increased risk for childhood leukemia was also found for children whose fathers eat 12 or more hot dogs per month. A higher-than-average meat intake was also found in a study of over 13,000 male Iowa farmers who experienced a 25% greater risk for leukemia, compared with individuals who were not farmers and consumed less meat. The risk for leukemia attributable to meat, particularly processed meat, may be related to the intake of nitrates used as preservatives, which are metabolized to highly carcinogenic N-nitroso compounds in the gut.
Recent studies have not supported a role for fruit and vegetable intake in leukemia prevention, although previous studies suggested such a link. The Iowa Women’s Health Study of more than 35,000 women found that the risk of leukemia was inversely associated with vegetable intake. In a study of 131 children with leukemia, higher maternal intake of fruits and vegetables was associated with a roughly 25% lower risk for ALL. Similarly, the Northern California Leukemia Study involving 138 children found an inverse association between maternal fruit and vegetable intake and ALL. This study also found that regular childhood intake of oranges, orange juice, and bananas was associated with roughly a 50% reduction in leukemia risk among children 2-14 years old.
Meta-analyses that compared breastfed with never-breastfed children found an 11% lower risk for childhood leukemia in the former group, and have estimated that 14%-19% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more.
Reviews of studies linking overweight or obesity have found that the risk for leukemia increases from a minimum of 28% greater in overweight women to 264% greater in obese men.
Tea consumption. Individuals who consume the most tea had an almost 45% lower risk for leukemia when compared with those consuming the lowest amount. These effects stem more from green than black tea. Proposed mechanisms include inhibition of anti-apoptosis proteins, triggering of apoptosis through free radical production, and VEGF receptor inhibition, among others.
Leukemias make up a family of blood cancers that have highly variable courses and treatment. Acute leukemias are rapidly fatal without treatment but may be curable with aggressive treatment. Chronic leukemias can be slow-growing; CLL may not need initial treatment, and CML can usually be controlled with oral therapy for years. Bone marrow transplantation is often considered for patients younger than 55 years. The role of the family is mainly to support the patient during diagnosis and treatment, which can often be difficult.
The role of diet in causing leukemia or influencing its course is not as clear as it is for solid tumors. Further research is required before specific dietary recommendations can be made.