Leukemias are malignancies of hematopoietic cells. About 60,000 new cases are diagnosed in the United States each year. The different types of leukemias are distinguished by the affected cell 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 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 years. 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 15-20% of leukemias in adults. As with AML, its median age at diagnosis is 65 years.1 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 are asymptomatic and are diagnosed 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 US 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, while CLL is especially prevalent in Eastern European Jewish populations.
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. A number of additional germline mutations are recognized to increase the risk of AML and may have implications for management.
Viral exposure. Certain rare subtypes of leukemia are associated with viral infections. This includes exposure to human T-cell lymphoma/leukemia virus (HTLV-1) in adult T cell leukemia/lymphoma and Epstein-Barr virus in Burkitt leukemia.
Radiation. 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. For AML, a number of germline mutations increase risk, and this has implications for screening family members.
A diagnosis of acute leukemia is made in the presence of ≥ 20% blasts in either the peripheral blood or bone marrow. Complete blood count with white blood cell (WBC) differential and examination of the blood smear 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. Bone marrow aspirate and biopsy with flow cytometry and genomic analysis is essential for full diagnosis and classification.
The classic diagnosis for CLL requires the presence of ≥ 5 × 109/L clonal B lymphocytes in the peripheral blood. Anemia or thrombocytopenia at presentation is correlated with a more aggressive clinical course. Peripheral flow cytometry is diagnostic, with further genomic analysis providing prognostic and therapeutic information.
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 the cases at presentation. Diagnosis is confirmed by demonstrating the presence of the Philadelphia chromosome, and bone marrow analysis can provide further prognostic information.
Treatment of AML is based on genomic risk stratification and a patient’s fitness to tolerate intensive treatment. AML is usually treated with combination chemotherapy although more targeted treatments are increasingly used. The goal of treatment is to induce complete remission, but the chances of cure range from 20 to 80% depending on the subtype. Allogeneic stem cell transplant is used for patients with high risk or relapsed disease.
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. An oral tyrosine kinase inhibitor targeting the abnormal fusion protein is the treatment of choice at diagnosis for the majority of patients who present in the chronic phase of CML, with the first-generation drug Imatinib most commonly used. Allogeneic stem cell transplant is very rarely required and is reserved for patients who have failed to respond adequately or tolerate a number of different tyrosine kinase inhibitors.
Many patients with CLL can be observed without immediate treatment (up to one-third never require treatment). When initiated, treatment now mostly involves a targeted oral agent with or without monoclonal antibody therapy. This may be for a fixed duration or continuous long-term treatment. 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 have a 37% greater risk for having a child who develops leukemia, and those with a body mass index between 25 and 30 have a 27% greater risk.
Western diet pattern. In a case-control study from Spain, a Western diet pattern was associated with a 63% increased risk of CLL.
Reducing or eliminating meat consumption. 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, a case-control study published in 2009 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 ate 12 or more hot dogs per month. A higher-than-average meat intake in a study of more than 13,000 male Iowa farmers was associated with 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.
High vegetable and fruit intake. Research has 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 25% lower risk of 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. A systematic review and meta-analysis of 18 case-control studies also found a decreased risk for ALL when consuming a Mediterranean-style dietary pattern, most notably with higher consumption of fruits, vegetables, and legumes.
Breastfeeding. 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. As part of the Pregnancy and Birth to 24 Months Project, a systematic review found that infants who were breastfed for short durations or not at all had a slightly higher risk for acute childhood leukemia, compared with those who were breastfed for longer than six months.
Healthy body weight. Studies show that the risk of leukemia increases by 28% in overweight women and by 264% in men with obesity.
Tea consumption. Based on a meta-analysis of one cohort study and six case-control studies, individuals in the US and China who consumed the most tea had an almost 45% lower risk for leukemia when compared with those consuming the least. 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.
Healthy diet and lifestyle during and after treatment. Many of the newer targeted treatments for leukemia increase the risk of cardiovascular disease including hypertension, heart arrythmias and heart failure. In addition, for individuals who are cured of acute leukemia, the greatest risk to future health is cardiovascular disease and second cancers. Therefore, adhering to the American Cancer Society guidelines for diet and physical activity is prudent. This includes a diet emphasizing fruit, vegetables, whole grains, and beans and limiting or avoiding red and processed meat and alcohol, and maintaining regular aerobic and resistance exercise. These habits support recovery from cancer treatment and also reduce the risk of future chronic conditions and solid cancers.
See Basic Diet Orders chapter.
What to Tell the Family
Leukemias are blood cancers that have highly variable courses and treatments. Acute leukemias are rapidly fatal without treatment but may be cured with aggressive treatment. Chronic leukemias can be slow growing. CLL may not need initial treatment. CML can usually be controlled with oral therapy for decades, with survival similar to the normal population.
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 formulated.
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