Page 2535 - Hematology_ Basic Principles and Practice ( PDFDrive )

2258 Part XIII Consultative Hematology

(RR, 1.16; 95% CI, 1.04–1.30; p = .007) and acute lymphoblastic even as an adjunct to conventional therapy. An in vitro study involv-
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leukemia (ALL) (RR, 1.62; 95% CI, 1.12–2.32; p = .009). Similar ing ALL cell lines demonstrated that red-wine polyphenols caused
results have been observed for children and adolescents with ALL and growth inhibition and apoptosis. Although these cell line experiments
AML. 35,36 Children and adolescents who were obese at diagnosis and often produce elegant results regarding mechanism of observed in
remained overweight/obese during treatment experienced reduced vitro action, whether the phytonutrients have the same benefits in
survival (hazard ratios, 1.43 and 2.30, respectively). Importantly, humans consuming the whole foodstuffs or concentrated supple-
those patients whose weight classification became a healthy weight ments remains uncertain. A large prospective study of over 120,000
eliminated this risk factor. Similar results have been reported in individuals with 17 years of follow up found no inverse relationship
children and adolescents with AML. of lymphoid or myeloid neoplasms and alcohol consumption; if
The second AICR recommendation is to be physically active for anything there was an increased risk rather than a decreased risk of
30 minutes every day. Although few studies have evaluated physical lymphoid neoplasms. 39
activity and hematologic malignancies, data suggest that low physical
activity may increase the risk of non-Hodgkin lymphoma (NHL) and
increasing activity may reduce the risk, especially for follicular and Supplements
small lymphocytic lymphoma.
The third recommendation is to avoid sugary drinks and limit Most conventional medical and radiation oncologists recommend
consumption of energy-dense foods. This is obviously linked with the that their cancer patients avoid all supplements, especially during
body-weight guideline because sugary drinks contribute many empty active radiation and chemotherapy. This recommendation is primar-
calories to the standard American diet. In addition, the contribution ily based on the absence of convincing data supporting therapeutic
of insulin and insulin-like growth factor type 1 to the development benefit. Three other valid concerns about supplement use are (1) the
of malignant disease is being increasingly appreciated in a number of potential for supplement–drug interactions via a pharmacokinetic or
cancers, leading to the investigation of blockade of the insulin-like pharmacodynamics pathway; (2) the oxidant–antioxidant issue; (3)
growth factor 1 receptor as a novel treatment for some malignant the impact of supplements on clotting, a particular problem for
diagnoses. High-sugar diets are tightly linked to obesity, thus adher- patients with hematologic malignancies on or off anticoagulants, and
ing to a diet low in simple sugars, such as the low-glycemic diet, may (4) purity or authenticity of the nutrition or herbal supplement.
not only reduce the risk of weight gain but also reduce risk of Concurrent use of a supplement, particularly a botanical, with
treatment-related toxicities during and after treatment. chemotherapy could lead to a clinically important interaction that
Fourth, the AICR suggests that people eat a greater variety of could yield an increase or decrease in the effects of either component.
fruits, vegetables, whole grains, and legumes such as beans. Data from Considering that 35% of currently prescribed oncology drugs are
the US Centers for Disease Control and Prevention demonstrate that metabolized by the CYP3A4 isoform of the hepatic cytochrome p450
the American public falls far short on the conservative recommenda- enzyme system, use of supplements that either induce or inhibit the
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tion to consume at least five servings of fruits and vegetables daily, pathway can be problematic. In treatment of hematologic toxicities,
with only 14% of adults meeting the guideline. Plants are rich sources cyclophosphamide, the epipodophyllotoxins, and the vinca alkaloids
of fiber, antioxidants, and phytonutrients, many of which are believed are all dependent of CYP3A4 for their metabolism. For example, the
to be useful in cancer-risk reduction. In one study, dietary fiber intake botanical supplement St. John’s wort used for the treatment of mild
was associated with a lower risk of all NHL subtypes. Another analysis depression is a strong inducer of many CYP isoforms. In a classic
found that high consumption of fruits and vegetables was associated pharmacokinetic interaction study, 10 healthy volunteers were
with a lower risk of all NHL subtypes, particularly follicular lym- administered a single 400-mg oral dose of imatinib before and after
phoma, in women but not men. 37 2 weeks of treatment with 300 mg of St. John’s wort three times daily.
Fifth, the AICR recommends limiting consumption of red meats The investigators found that the pharmacokinetics of imatinib were
(beef, pork, and lamb) and avoiding processed meats. Epidemiologic significantly altered by St. John’s wort, with reductions of 32% in the
studies suggest that consumption of fried red meats as well as dairy median area under the concentration–time curve (p = .0001), 29%
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products leads to an increased risk of NHL. Conversely, consump- in maximum observed concentration (p = .005), and 21% in half-life
tion of higher levels of omega-3 or marine fatty acids has been (p = .0001). The conclusion was that coadministration of St. John’s
shown to be inversely correlated with lymphoma risk. Additional wort might compromise the clinical efficacy of imatinib. It is gener-
studies in an Australian cohort suggest that a diet high in fish may ally recommended that cancer patients receiving any intervention
also be protective against the development of other hematopoietic avoid taking St. John’s wort.
malignancies—leukemias and multiple myeloma as well as NHL. 38 Patients with hematologic malignancies are often at increased risk
Sixth, the AICR guidelines state that if consumed at all, alcoholic for bleeding problems. A small case series performed among children
drinks should be limited to two for men and one for women per day. with cancer suggests that the Chinese herb Yunnan Baiyao may allevi-
Although moderate alcohol consumption may be associated with ate uncontrollable bleeding in patients with cancer; however, clinical
cardiovascular benefits, alcohol use has been associated with an trials are not yet available to confirm the findings of this case series.
increased risk of a number of malignancies. A pooled analysis of nine There has been a long-standing tendency to attribute thrombocyto-
case-control studies of NHL revealed that ever drinkers, compared penias of unclear etiology in cancer patients to botanical supplements
with never drinkers, had a 17% lower risk of NHL, a finding the that they are taking, particularly traditional Chinese medicine herbs.
investigators attributed to a possible beneficial effect of moderate It is critical that the use of Chinese herbal products is accompanied
alcohol consumption on immune function. A cohort study in by a certificate of authenticity to ensure purity and absence of
126,293 multiethnic adults used lifelong abstainers and infrequent contamination.
drinkers as the referent and reported a relative risk of 0.5 for the Warfarin is a frequently prescribed anticoagulant, itself derived
development of both lymphocytic and myeloid leukemias in those from a botanical, which can be impacted in a number of ways by diet
consuming three or more drinks daily without any contribution of and dietary supplements. Inappropriate control of anticoagulation
choice of beverage (wine, beer, or liquor). With regard to patients because of fluctuation in warfarin effect exposes the patient to risks
already diagnosed, a cohort of 575 female NHL cases in Connecticut of increased bleeding or thromboembolic complications. Warfarin is
was followed for a median of 7.75 years. Compared with never metabolized by the cytochrome p450 system isoforms, including
drinkers, wine drinkers experienced better overall survival (75% vs. CYP3A4. In addition, it is also highly protein bound and hence can
69% five-year survival; p = .030) and disease-free survival (70% vs. interact with medications or supplements that are also highly protein
67%; p = .049). The favorable effect for wine drinkers was seen bound, resulting in displacement and causing increases in inter-
mainly in patients with diffuse large B-cell lymphoma. Resveratrol, a national normalized ratio (INR) and necessitating warfarin dose
red-wine polyphenol known for its potential cardioprotective effects, reduction. Finally, the anticoagulant effect of warfarin can be antago-
is also believed to have potential in cancer risk reduction and perhaps nized by vitamin K intake. Patients prescribed warfarin are often