, a category of blood diseases also referred to as )
BRAVE FACE: Nora Ephron at the 2010 Tribeca Film Festival. She was first diagnosed in 2006 with a type of myelodysplastic syndrome (MDS), a category of blood diseases also referred to as "preleukemia." This later progressed to acute myeloid leukemia (AML).
Image: Courtesy of David Shankbone, via Wikimedia Commons
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Nora Ephron's final act played out in Manhattan on June 26 where the 71-year-old writer and movie director died from pneumonia brought on by acute myeloid leukemia (AML), one of the most common types of leukemia among adults. AML is a cancer caused when abnormal cells grow inside bone marrow and interfere with the production of healthy blood cells. The marrow eventually stops working correctly, leaving a person with an increased risk of bleeding and infections.
Ephron—best known for writing When Harry Met Sally and Sleepless in Seattle—was first diagnosed in 2006 with one of the myelodysplastic syndromes (MDS), a category of blood diseases also referred to as "preleukemia" that can progress into AML if the bone marrow continually fails to produce enough healthy platelets, red blood cells and white blood cells over time. MDS made headlines recently when ABC's Good Morning America anchor Robin Roberts announced she has been diagnosed with the disease.
Some types of leukemia, including AML, develop as a result of exposure to certain chemicals (including herbicides and pesticides), chemotherapy drugs (such as etoposide and a class of drugs known as alkylating agents) and radiation. Typically, however, a doctor is unable to pinpoint the exact cause in individual cases.
Although estimates vary, there are between 10,000 and 12,000 new cases of MDS in the U.S. annually. More than 80 percent of all MDS patients are older than 60. The National Cancer Institute projects that 13,780 men and women—7,350 men and 6,430 women—will be diagnosed with AML and that 10,200 men and women will die of the malady this year.
Scientific American spoke with Bart Scott, a medical oncologist specializing in the treatment of patients with MDS, about syndrome's progression to AML, who is most at risk for this cancer and whether there are any promising treatments on the horizon. Scott is also director of hematology and hematologic malignancies at the Seattle Cancer Care Alliance and an assistant member of the Fred Hutchinson Cancer Research Center's clinical research division.
[An edited transcript of the interview follows.]
What is the typical trajectory for this form of cancer?
The trajectory of myelodysplastic syndrome is highly dependent upon two factors—the bone marrow myeloblast count and the cytogenetics. [A myeloblast is an immature blood cell that will eventually develop into a type of white blood cell.] The higher the bone marrow myeloblast count is at time of diagnosis the more likely a patient is to progress to acute myeloid leukemia. In general, the more abnormal the cytogenetics [a cell's hereditary and functionalm characteristics] are the more likely a patient is to progress to AML, but there are certain abnormalities that have a good prognosis.
Who are the typical victims of this form of leukemia?
The median age of diagnosis of MDS is 72, it is slightly more common in men than women, and there is a correlation between incidence and age. I would say that Ephron's course does seem consistent with MDS progression to AML.
What are the risk factors for this cancer?
They are based on increasing age as well as certain environmental exposures like pesticides and herbicides. This is not casual contact—we are talking about prolonged, persistent exposure. The amount of exposure required to cause the disease is unknown, however.
Given that Ephron lived most of her life in New York City, whose residents are not typically exposed to inordinately large amounts of pesticides or herbicides, what might account for her condition?
Some researchers have tried to understand MDS in terms of clustering, although there is very little clustering data available. The idea is to understand whether MDS tends to cluster in areas of higher exposure to certain toxic agents. In 2007 Xiaomei Ma [an associate professor of epidemiology the Yale School of Public Health] and a team of researchers published a paper in Leukemia Research regarding this phenomenon. They found that cases of MDS in Connecticut were clustered near the western border. In general, clustering supports the idea that environmental exposure is contributory to the development of a disease. This is the only paper that I know of that has demonstrated clustering in MDS.
We are doing a similar study in the state of Washington. Hanford Site is a nuclear production complex near the Tri-Cities area in southeastern Washington [encompassing Kennewick, Pasco and Richland]. We are looking to see if there is clustering in the Tri-Cities area. But these studies are difficult given the mobility of the area's population, unknown exposure time and any delay in the development of MDS after exposure.
What is the usual treatment?
There are three FDA approved treatments. One is azacitidine, approved by the FDA in 2004 and marketed as Vidaza. Decitabine, sold as Dacogen and approved in 2010 to treat MDS, is another option. [The FDA's oncologic drugs advisory panel in February, however, recommended against the approval of Dacogen to treat older patients with AML. The drug's maker wants FDA approval to use Dacogen in AML patients 65 years and older and who are not considered good candidates for high-dose chemotherapy as an initial treatment for AML.] The third is lenalidomide, also known as Revlimid and introduced in 2004.
However, the only curative treatment is stem cell transplantation. Stem cells are infused just like a blood transfusion. Sources of stem cells include cord blood cells, peripheral blood mobilized stem cells or bone marrow. Success depends on the stage of disease. The one-year treatment related mortality is approximately 20 percent. If patients are transplanted in an early stage of the disease, we have a success rate of 80 percent.
Are there any promising treatments in late-stage testing?
Yes, there are several drugs being investigated in phase II and phase III trials. We currently have a phase III trial open with a drug called rigosertib for patients who have failed prior treatment with azacitidine or decitabine, which are known as demethylating agents. The proposed mechanism of action for these drugs is that they alter gene expression profiles in the cancer cells and increase their susceptibility to death. Rigosertib is a cell cycle inhibitor and would prevent the cancer cells from growing and induce direct damage to the cancer cells, causing their death.
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16 Comments
Add CommentOnce again, Oncological Terrain-Dependent Inherited Real Risk of cancer, both solid and liquid, I discovered 10 years ago, is overlooked (Ask Google.com or see Bibliography in my website: Login is not requested!). Present at birth and bedside recognised with a stethoscope in one second in quantitative manner, every Inherited Real Risk disappears "generally", i.e., almost all, under no expensive treatment, illustrated now in a large Literature.
Reply | Report Abuse | Link to thisOne thing which is common to both ageing and leukemia is the metal iron. Ageing leads to 'age-related iron accumulation'.
Reply | Report Abuse | Link to this"Iron accumulates with senescence in several organs"
Leukemia and the iron loading disease polycythemia are closely related.
"Progression to acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) is a possible evolution of polycythemia"
Leukemia and the iron loading disease aplastic anemia are closely related.
"PRCA can evolve into aplastic anemia and acute myelogenous leukemia"
Targeting of iron leads to full recovery in aplastic anemia.
"Complete recovery after iron chelation in aplastic anemia"
Iron reduction / phlebotomy is the treatment for polycythemia.
"Phlebotomy or bloodletting has been the mainstay of therapy for the polycythemia vera (PV) disease process for a long time"
The first order of business would be to discover whether increased storage of iron is what leads to leukemia ?
What would be the rate of leukemia in those with the iron disease , hemochromatosis ?
"This suggests that the increased cancer risk is more likely due to the effects of iron"
Iron loading parallels the risk of cancer? Well. But what accounts for the reason only a small percentage of people accumulate Iron, suffering from Iron loading and perhaps they are at risk of cancer?
Reply | Report Abuse | Link to thisQuote: But what accounts for the reason only a small percentage of people accumulate Iron
Reply | Report Abuse | Link to thisAnswer: Actually , it is reaching "epidemic proportions".
Older people are KNOWN to be iron overloaded.
"Elderly people in Taiwan are an iron-replete population with a high prevalence of elevated iron stores and a low prevalence of iron deficiency"
"Excessive body iron or iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which are reaching epidemic levels worldwide."
Quote: perhaps they are at risk of cancer?
Answer: Yes. Iron chelators are being used and developed as we speak.
"Iron chelators in cancer chemotherapy"
"The role of iron chelation in cancer therapy"
In my one Country, Italy, the majority of old population, including myself, show a perfect Iron metabolism. In addition, Cancer can involve individuals with Oncological Terrain.
Reply | Report Abuse | Link to thisThis study shows by targeting the iron , leads to targeting of the progenitors , which means , targeting the iron results in targeting the beginning OF the leukemia.
Reply | Report Abuse | Link to this"Selective toxicity towards myelodysplastic hematopoietic progenitors – Another rationale for iron chelation in MDS"
THIS study , coincidentally , shows a child on the verge of death , recovering , by targeting the iron.
"Complete hematopoietic recovery after continuous iron chelation therapy in a patient with severe aplastic anemia with secondary hemochromatosis"
Quote: In my one Country, Italy, the majority of old population, including myself, show a perfect Iron metabolism
Reply | Report Abuse | Link to thisAnswer: Thalassemia is very big in Italy.
"Because of its high prevalence in Italy, thalassemia is officially considered a disease of major social importance"
I suspect you are incorrect in your assessment of the iron in your country.
My dear, Italy is more than Sardegna and Sicilia! In addition, according to you, is thalassemia a risk factor of cancer?
Reply | Report Abuse | Link to thisYes , Thalassemia is an iron loading disease.
Reply | Report Abuse | Link to this"Thalassemia patients overproduce a protein called GDF15, which suppresses the production of a liver protein, hepcidin, which in turn leads to an increase in the uptake of dietary iron in the gut"
Increased iron leads to increased cancer.
"Hepatocellular carcinoma in thalassemia: A critical review."
Iron reduced people did not progress to hepatocellular carcinoma.
"Normalization of Elevated Hepatic 8-Hydroxy-2'-Deoxyguanosine Levels in Chronic Hepatitis C Patients by Phlebotomy and Low Iron Diet"
"None of these patients developed hepatocellular carcinoma"
Cancer is more than a problem of Iron pathological deposit in tissue. Cancer is today's growing epidemics, in spite of Iron metabolism impairment. Cancer can occur exclusively in presence of Oncological Terrain-dependent Inherited Real Risk, even in individuals showing normal, physiological Iron metabolism.
Reply | Report Abuse | Link to thisQuote: even in individuals showing normal, physiological Iron metabolism
Reply | Report Abuse | Link to thisAnswer: THAT is where we disagree. Noone , who eats meat , is IN this state of 'normal, physiological Iron metabolism'.
The human controls the iron levels in the body at the point of absorption. The human body has no effective method of decreasing iron in the body. Meat iron / heme iron , that iron found in blood , slips in the 'back door' so to speak and is absorbed at all times of iron status. Meaning , even though the body is trying to NOT absorb iron , enough on board , this blood iron slips right on past and begins to build in the body, IE: age-related iron accumulation. EVERY meat eater has elevated iron levels.
Evidence based medicine , IE: recovery , gives evidence to the Herbivore Hypothesis . If iron reduction , targeting iron works , it works. Can't get around it.
The reason you believe there IS such a thing as a
Reply | Report Abuse | Link to this"normal, physiological Iron metabolism" in people who eat meat is because of what the medical profession believes IS a state of 'normal, physiological Iron metabolism'.
Wrong thinking.
What the medical profession has accepted as low normal hemoglobin is , in fact , normal.
All people who are diagnosed iron deficient are either normal or in a state of 'anemia of chronic disease' in which the body withholds iron to prevent an 'enemy' , virus , bacteria , parasites from acquiring the iron. Lactoferrin is the iron remover. When saturated or partially saturated with iron the lactoferrin cannot do its' job of removing the iron , efficiently ENOUGH.
"Antimicrobial and antiinflammatory effect of lactoferrin by chelation of iron"
THIS is an example of the difference meat causes , increased hemoglobin , compared to a vegetarian.
"Re-introduction of beef into the diets of the beef group increased hemoglobin concentration and hematocrit compared with the vegetarian group"
http://www.ncbi.nlm.nih.gov/pubmed/12728219
The higher the hemoglobin , is NOT "better". Oxygenation of the blood is carried about by vitamin E , it governs the amount of oxygen carried in the red blood cell. So , technically , a man with plenty of vitamin E , but no red blood cells , would carry more oxygen than a man with more red blood cells but no vitamin E. This 'paradox' has been shown in long distance runners who with a hemoglobin of 9 beat everyone in the race and are shown to have increased oxygen carrying capacity.
Doctors have a 'window' in which a person is normal for hemoglobin , low normal to high. The 'high' is governed by a statistic , which would rule out 'false positives' for hemoglobin too high. The problem being higher hemoglobin , what is accepted as normal , kills dialysis patients , PROVING , to me at least , normal hemoglobin is bad. But that's just me.
12.5 kills and normal is 13.
"Haemoglobin above 125 g/l is associated with an increase in mortality"
"Normal hemoglobin levels are 120 to 160 g/L for adult women and 130 to 180 for men (equivalent American values are 12 to 16 g/dL for women and 13 to 18 g/dL for males)."
This is a recent study of children. You will notice the hemoglobin accepted as normal in the boys is only two notches below diagnosing of polycythemia in a full grown man and also is two and half notches above being dead if on dialysis ? "14.9 ± 1.1 g/dL" versus death at 12.5 ± 1.1 g/dL ?
Reply | Report Abuse | Link to this"We demonstrated that Hb levels in boys increased with age during childhood and adolescence (from 13.1 ± 0.7 g/dL in 7 year olds to 14.9 ± 1.1 g/dL in 15 year olds); in girls, Hb levels peaked at menarche (13.7 ± 0.8 g/dL in 12 year olds), decreasing slightly thereafter (13.4 ± 1.1 g/dL in 15 year olds)."
http://www.ncbi.nlm.nih.gov/pubmed/22791127
"You may have eaten the equivalent of one whole I-beam from the Brooklyn Bridge."
Reply | Report Abuse | Link to thishttp://www.kidsneedusnow.org/public_html/kids_pages/cereal_magnets.html
"WALL STREET JOURNAL-MAY 17,1994"
"Since 1983, researchers have warned us to avoid supplements that contain iron may be a primary cause of free radical induced degenerative disease.
In a study in the March 29,1994 issue of the Proceedings of the National Academy of Sciences, Japanese researchers found that iron caused tubular
necrosis (kidney damage), leading to a high incidence of renal adenocarcinoma (kidney cancer).
This is not an isolated study - just another of the multitude of studies showing that iron is a cause of the diseases that kill us.
The FDA requires that food companies fortify many products with iron, which causes most Americans to get too much iron from their diet."
Hi,
Reply | Report Abuse | Link to thisThis an awesome information found here about Nora Ephron's health. Really great post. I liked it.
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Regards,
Marc
Although mainly overlooked, Oncological Terrain-Dependent, Inherited Real Risk of leukemia does really exist. It is bedside diagnosed,i.e., with a simple stethoscope, from birth and now almost always eliminated with Quantum Therapy:Simone Caramel and Sergio Stagnaro Quantum Biophysical Semeiotics of Oncological Inherited Real Risk of Myelopathy: The diagnostic role of glycocalyx. http://www.sisbq.org/uploads/5/6/8/7/5687930/qbs_myelopathy_glycocalyx_english.pdf
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