Leukemia

Aspartame is linked to leukemia and lymphoma in new landmark study on humans

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As few as one diet soda daily may increase the risk for leukemia in men and women, and for multiple myeloma and non-Hodgkin lymphoma in men, according to new results from the longest-ever running study on aspartame as a carcinogen in humans. Importantly, this is the most comprehensive, long-term study ever completed on this topic, so it holds more weight than other past studies which appeared to show no risk. And disturbingly, it may also open the door for further similar findings on other cancers in future studies.

The most thorough study yet on aspartame – Over two million person-years

For this study, researchers prospectively analyzed data from the Nurses’ Health Study and the Health Professionals Follow-Up Study for a 22-year period. A total of 77,218 women and 47,810 men were included in the analysis, for a total of 2,278,396 person-years of data. Apart from sheer size, what makes this study superior to other past studies is the thoroughness with which aspartame intake was assessed. Every two years, participants were given a detailed dietary questionnaire, and their diets were reassessed every four years. Previous studies which found no link to cancer only ever assessed participants’ aspartame intake at one point in time, which could be a major weakness affecting their accuracy.

One diet soda a day increases leukemia, multiple myeloma and non-Hodgkin lymphomas

The combined results of this new study showed that just one 12-fl oz. can (355 ml) of diet soda daily leads to:

– 42 percent higher leukemia risk in men and women (pooled analysis)
– 102 percent higher multiple myeloma risk (in men only)
– 31 percent higher non-Hodgkin lymphoma risk (in men only)

These results were based on multi-variable relative risk models, all in comparison to participants who drank no diet soda. It is unknown why only men drinking higher amounts of diet soda showed increased risk for multiple myeloma and non-Hodgkin lymphoma. Note that diet soda is the largest dietary source of aspartame (by far) in the U.S. Every year, Americans consume about 5,250 tons of aspartame in total, of which about 86 percent (4,500 tons) is found in diet sodas.

Confirmation of previous high quality research on animals

This new study shows the importance of the quality of research. Most of the past studies showing no link between aspartame and cancer have been criticized for being too short in duration and too inaccurate in assessing long-term aspartame intake. This new study solves both of those issues. The fact that it also shows a positive link to cancer should come as no surprise, because a previous best-in-class research study done on animals (900 rats over their entire natural lifetimes) showed strikingly similar results back in 2006: aspartame significantly increased the risk for lymphomas and leukemia in both males and females. More worrying is the follow on mega-study, which started aspartame exposure of the rats at the fetal stage. Increased lymphoma and leukemia risks were confirmed, and this time the female rats also showed significantly increased breast (mammary) cancer rates. This raises a critical question: will future, high-quality studies uncover links to the other cancers in which aspartame has been implicated (brain, breast, prostate, etc.)?

There is now more reason than ever to completely avoid aspartame in our daily diet. For those who are tempted to go back to sugary sodas as a “healthy” alternative, this study had a surprise finding: men consuming one or more sugar-sweetened sodas daily saw a 66 percent increase in non-Hodgkin lymphoma (even worse than for diet soda). Perhaps the healthiest soda is no soda at all.

New Diagnostic Test for Blood Cancers Will Help doctors.

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Pictured: Ross Levine
Physician-scientist Ross Levine

A new diagnostic test that identifies genetic alterations in blood cancers will enable physicians to match patients with the best treatments for leukemias, lymphomas, and myelomas. Co-developed by Memorial Sloan-Kettering and cancer genomics company Foundation Medicine, the test analyzes samples from patients with the blood diseases and provides information about hundreds of genes known to be associated with these disorders.

The genetic profile will help physicians make more-accurate prognoses and also guide them in treatment recommendations — from deciding whether to take an intensive approach with existing drugs such as chemotherapy to enrolling patients in clinical trials investigating novel therapies. The new test is produced commercially by Foundation Medicine and is expected to be available by the end of this year.

Medical oncologist Ross Levine, who led research at Memorial Sloan-Kettering contributing to the development of the test along with physician-scientists Marcel van den Brink, Ahmet Dogan, and Scott Armstrong, presented results demonstrating its accuracy today at the annual meeting of the American Society of Hematology in New Orleans.

A Tool with Broad Impact

The test will play an essential role in the clinical care of most patients with blood disorders at Memorial Sloan-Kettering and, it is expected, in the care of patients throughout the United States. According to the Leukemia and Lymphoma Society, an estimated 1.1 million people in the nation are currently living with, or in remission from, leukemia, lymphoma, and myeloma, and an estimated combined total of more than 148,000 will be diagnosed with one of these diseases in 2013.

“Our hope is that this test becomes available to all patients in the country with these malignancies,” Dr. Levine says. “We were particularly excited that we weren’t just developing a tool for the relatively small number of people who are treated at our institution, but providing access to state-of-the-art cancer genomics more broadly.”

The diagnostic test was developed and validated using more than 400 samples from Memorial Sloan-Kettering patients with the three blood disorders. Dr. Levine explains that it is far more comprehensive than existing tests, which focus on a small number of genetic mutations associated with specific blood cancer types. The new test analyzes more than 400 cancer-related genes, and unlike most standard tests, it looks for alterations in both DNA and RNA.

Sequencing RNA along with DNA is especially useful in the detection of certain kinds of genetic alterations that commonly occur in blood cancers. These include translocations (which occur when pieces of DNA are exchanged between two chromosomes) and fusion genes (new genes that include parts of two different genes). In addition to improving the treatment of patients, Memorial Sloan-Kettering will use information gleaned from the test to further advance research into blood cancers.

Clinically Relevant Mutations

Dr. Levine explains that Memorial Sloan-Kettering researchers worked with Massachusetts-based Foundation Medicine to annotate, or define, every gene in the panel to correlate it with clinical data and to provide insight into how this information can be used to guide clinical decision making.

“What’s vital about the test is that it’s not just reporting the presence of specific alterations but also indicating how a particular genetic event detected in a patient can guide either prognosis or therapy,” he says. “We identified clinically relevant mutations that were not found using standard tests. These mutations are ‘actionable,’ meaning that targeting them can change the course of the disease, including directing patients to innovative clinical trials.”

Initially, the goal for the test is to produce the full genetic profile from a patient sample within three to four weeks. “With the exception of someone who has very acute leukemia that requires immediate treatment decisions, this test is going to be valuable in clinical care,” Dr. Levine says.

 

Vaccine stirs immune activity against advanced, hard-to-treat leukemia.

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Novel treatment boosted selective immune attack on leukemia cells in post-transplant patients

Patients with advanced chronic lymphocytic leukemia (CLL) often receive donor transplants that effectively “reboot” their own immune defenses, which then attack and potentially cure the hard-to-treat disease. However, there is a high rate of relapse in these patients, and the transplanted immune cells may also harm normal tissues, causing graft-versus-host disease (GVHD).

Now, scientists at Dana-Farber Cancer Institute report in the Journal of Clinical Investigation that they observed a strong and selective immune response in some patients who received, shortly after the transplant, several doses of a “personalized” tumor vaccine composed of their own inactivated leukemia cells combined with an immune stimulant, GM-CSF. Thus the vaccine boosted the power of the transplanted immune system’s ability to attack the cancer – known as the graft-versus-leukemia (GvL) effect.

“Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control” following transplants from donors, saidCatherine Wu, MD, senior author. “Although this was a phase 1 study and not powered to look at questions of clinical efficacy, we did see promising clinical activity.”

There are few treatment options for advanced CLL. Standard transplants, which involve powerful doses of pre-transplant chemotherapy to wipe out as much of the leukemia as possible, have proven too toxic for older patients and those with co-existing diseases. Over the past decade, researchers have developed reduced-intensity conditioning (RIC) regimens, using lower chemotherapy doses that are more tolerable but which rely entirely on the activity of the transplanted immune cells to battle the leukemia. Usually this is insufficient to keep the cancer at bay long-term and the disease progresses.

Furthermore, research has shown that the identifying antigens on the surface of CLL cells in individual patients may differ – that is, they have “personal tumor antigens,” the scientists said. “Based on these principles, vaccination with autologous [the patient’s own stored leukemia cells] irradiated leukemia cells is an attractive approach to expand leukemia-reactive T cells, since this vaccine formulation reliably includes personal tumor antigens.”

To make the vaccine, the researchers mixed the patients’ irradiated leukemia cells with cells that produce GM-CSF (granulocyte-macrophage colony-stimulating factor) and then injected them back into the patient. The combination stirs up a strong response by immune T cells, and the distinctive antigens on the injected leukemia cells direct the T cells to attack similar leukemia cells wherever they are present in the body.

In the phase 1 trial, the vaccine was administered between 30 and 100 days after the transplant, with some patients receiving as many as six vaccine doses. The study enrolled 22 patients with advanced, aggressive CLL. Thirteen of the patients had evidence of the leukemia in their bone marrow at the time of transplant.

Four patients did not receive the vaccine because they developed GVHD following the transplant. The remaining 18 received at least one vaccine dose; seven patients stopped receiving the vaccine after they developed GVHD.

When examined six months post-transplant, the majority of patients showed evidence of clinical response: 10 had complete remissions and six had partial remissions. After a median follow-up of 2.9 years, 13 patients (72 percent) had remained in continuous complete remission; one patient had stable disease, three patients developed progressive disease and two of those patients died.

The results support the safety and biological activity of whole tumor-cell vaccination in hematological malignancies, said the authors, and that giving the vaccine shortly after transplant may have been critical in its effectiveness. In addition, they said a key to the vaccine’s potency was the development by Dana-Farber scientists of GM-CSF-secreting “bystander” cells that can be used against lymphoid malignancies – which was not possible previously.

However, the authors noted that further randomized studies in larger patient groups will be necessary to determine if this strategy “will translate into a true clinical benefit for patients with advanced CLL.”

Source:DFCI

Genomic Studies Allow Better Classification of Leukemias, Endometrial Tumors.

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Two studies, one of leukemia and the other of endometrial tumors, show the usefulness of genomics studies in finding unsuspected classifications, possibly useful for treating these cancers.

One study, published in the New England Journal of Medicine, examined 200 cases of acute myeloid leukemia. Genomic studies allowed the researchers to discern nine distinct categories, revealing “many potentially important biologic relationships.” For instance, certain mutations were associated with distinct patterns of RNA activity. The authors point out that the significance of such findings “is not yet clear.”

Another study, in Nature, of some 375 endometrial cancers found four distinct classes of the disease, as opposed to the two commonly used to stage treatment. In Journal Watch Oncology and Hematology, Virginia Kaklamani observes that breast cancer was the first to use molecular subtypes to guide treatment. The Nature study, she writes, is “a huge step toward applying this technique in other malignancies.”

Source:NEJM