Hope for Acute Myeloid Leukemia: Facts and Options
- AML is the most common type of acute leukemia in adults.
- Despite advances in the scientific understanding of this cancer, survival has not markedly increased over the last 3 decades.
- Understanding AML, its risk factors, treatment options and integrative approaches can help you learn which questions to ask your doctors and how to stack the deck in your favor.
by Dr. John Neustadt
When people learn they or a loved one has cancer, one of their first questions is usually about survival. Fortunately, more people are now surviving many cancers that used to be death sentences. The American Cancer Society’s Cancer Statistics reports that death rates have continued to decline for all four major cancer sites: lung, colon and rectum (colorectal), breast, and prostate. The drops are evidence of the power of prevention and early detection. Decreases in deaths from these cancers were primarily due to reductions in smoking for lung cancer and to improvements in early detection and treatment for colorectal, breast, and prostate cancers.
However, while increased survival rates for people with those cancers is encouraging, those advances have not extended to acute myeloid leukemia (AML). Acute Myeloid Leukemia (AML) is a cancer of the bone marrow in which growing white blood cells are stuck in an early stage of development. Frequently AML develops from Myelodysplastic Syndrome (MDS). While there are different diagnostic criteria for MDS and AML, they are the same disease process and are differentiated primarily their severity.
MDS and AML are diseases of deficient blood production. A blast cell is an immature white blood cells produced in bone marrow. There are different subtypes of AML, which are distinguished from other related blood disorders by the presence of more than 20% blast cells in the bone marrow. MDS is differentiated by AML by having a lower percentage of blast cells. The underlying development of AML and MDS consists of bone marrow cells getting stuck in the earliest stages of development.
This inability for the bone marrow to produce healthy blood cells results in two disease processes. First, the production of normal blood cells markedly decreases, which results in varying degrees of anemia, thrombocytopenia (low platelets), and neutropenia (low neutrophils). Second, the natural life cycle of the cells is interrupted. Cell typically die and are regenerated at regular intervals. But with cancer, including AML, this process of programmed cell death (apoptosis) doesn’t happen. Instead of cells dying and being recycled by the body, these cells accumulate in the bone marrow, blood, and, frequently, the spleen and liver.
AML is the most common type of acute leukemia in adults. Decades of research looking at the development and prognosis of AML have made revolutionary progress. However, despite an increase in the ability to diagnose AML and a greater understanding of the disease process, improvements in patient outcomes have not paralleled the increases in basic scientific understanding.
According to the National Cancer Institute (NCI), mortality from AML has not decreased. To the contrary, for both men and women, the death rate from AML over the last three decades has gone up. This may partially be due to the fact that treatment for other cancers using chemotherapy and radiation can cause MDS and AML to develop years later. These types of MDS and AML are called therapy-related MDS (t-MDS) and therapy-related AML (t-AML) and they are more aggressive forms of cancer.
Tragically, two-thirds of all adult AML cases cannot be cured. Even with aggressive treatment, the average time to death after diagnosis with AML is one year, and about 10% of patients die from the initial round of AML therapy. Thus, new strategies to promote health in people with AML are desperately needed. Healthcare providers trained in integrative oncology are now using dietary recommendations, lifestyle changes and nutrition in conjunction with conventional approaches to help reduce chemotherapy and radiation therapy side effects, promote the immune system, and improve quality of life and feelings of well-being, energy and mood.
Fortunately, more and more studies are evaluating the potential benefits of using nutrients to help promote health in people with AML and other cancers. MK4 is an example of the potential benefits of an integrative approach. As a supportive nutrient, MK4 is the only form of vitamin K shown to help. Fourteen clinical trials and case reports evaluated the ability of MK4 to promote healthy cells in nearly 600 people with cancer. Additionally, laboratory research has studied MK4’s effects on isolated cancer cells. Conclusions of this research showing the potential benefits of this nutrient for people with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) liver cancer (hepatocellular carcinoma) and acute promyelocytic leukemia have been published in more than 15 medical journals.
These studies were also evaluated by the U.S. FDA’s Office of Orphan Products Development (OOPD). The term orphan as used by the FDA means a rare condition. The FDA evaluates data on products that might have the potential to help people. If FDA scientists agree that the studies submitted support the potential use of the product, they approve a special status called Orphan Designation.
Dr. John Neustadt submitted the data to the FDA on MK4 to help people with AML, MDS, liver cancer and promyelocytic leukemia, and FDA scientists agreed that for all of these designations, MK4 has the potential to help people. The FDA granted Orphan Designation for MK4. And while MK4 is not approved as a medication and is not a drug approved for treating or preventing any disease, it is available as a natural product in dietary supplements to help promote healthy cell division and support healthy blood production.
But before people consider if an integrative approach to their healthcare is best for them, it’s important to understand how conventional medicine treats AML. Armed with information, people can better understand which questions to ask their doctors so they can fully grasp their options and make the best decisions possible for their health.
Causes of AML
AML is caused by DNA damage to cells in the bone marrow. In most cases, it’s not clear what causes the DNA mutations that lead to leukemia. However, previous cancer treatments and environmental pollution both cause AML, MDS and other cancers.
Previous Cancer Treatments
Cancer is caused by cumulative DNA damage. Earlier detection of cancers has led to earlier treatment with chemotherapy and radiation therapy, which causes further DNA damage. While people are surviving longer with many cancers due to more aggressive treatments, the treatments themselves can cause MDS and AML to develop years later. When MDS and AML are caused by treatment of a previous cancer they are called therapy-related MDS (t-MDS) and therapy-related AML (t-AML). It’s estimated that up to 20% of AML cases are caused by previous cancer treatments. More than 70% of patients who develop therapy-related leukemia develop t-MDS first.
And when t-MDS/t-AML develops, it’s a more aggressive form of cancer and tends to be resistant to treatment. The median survival in one study of t-MDS/t-AML patients was eight months and only 10% of patients were alive after five years.
Of those people t-AML caused by previous cancer therapy, breast cancer was the most common initial cancer diagnosis. In one study, 52% of new therapy-related AML diagnoses were in women who had been previously treated for breast cancer. AML typically developed four years after breast cancer treatment. Up to 14% of lymphoma and Hodgkins patients who undergo autolagous bone marrow transplant develop t-MDS/t-AML as early as three years after the procedure. This may be due to chemotherapy, total body irradiation, and the extensive cellular proliferation which occurs during the transplant.
The time between the initial cancer treatment and development of t-MDS/t-AML varies from approximately two years to eleven years, depending on the type of treatment used. While patients can be diagnosed with t-MDS/t-AML at any age, the median age at diagnosis is 61 years.
Toxins in our environment are known causes of MDS and AML. Exposure to the chemical benzene causes AML. Benzene is used as a solvent and is found in petroleum products and used in the rubber industry. It’s also present in cigarettes, which may explain why smokers are three times more likely to develop AML than non-smokers.
Radon is a naturally occurring radioactive gas. It’s produced from the breakdown of uranium in soil and rocks. When the gas is released outdoors it can dissipate and is harmless. However, if homes sit on top of deposits that release radon gas, it can concentrate in homes and cause problems. In addition to radon gas is a known risk factor for lung cancer, it has also been shown to increase AML risk.
As with therapy-related leukemia, exposure to high levels of environmental radiation is also a risk factor. People who spend long periods of time in airplanes may also be more at risk because the high altitude provides less protection against the sun’s radiation. Commercial airline pilots were shown in one study to have an increased risk of AML due to their increased radiation exposure.
Frequently there are no symptoms at first and leukemia may be a chance finding on a blood test. When symptoms do appear, they may be vague and non-specific, similar to a flu-like illness.
- Generalized weakness and fatigue
- Anemia and the person may appear pale, weak and tired.
- Frequent infections, fevers, chills or flu-like symptoms
- Weight loss
- Excessive or easy bruising or bleeding
- Pain in the bones and joints
- Easily becoming out of breath
- Enlarged lymph nodes, liver and/or spleen tender to the touch
- Abdominal discomfort
- Night sweats
- In men, swollen testicles
- Headaches, seizures and vomiting can occur if the spinal column is affected
Different types of leukemia develop in different ways. Acute leukemias progress rapidly, whereas in chronic leukemia the symptoms take longer to develop and the physical decline people experience is slower.
Conventional Approaches to AML
There are three general categories of AML treatment phases: Induction, Consolidation, and Maintenance therapies. The treatment of patients with AML includes at least one course of intensive myelosuppressive induction chemotherapy. Myelosuppressive means that substances are given to decrease the production of blood cells in the bone marrow.
Cytarabine (AraC) is the cornerstone of induction therapy and consolidation therapy for AML. A standard form of induction therapy consists of AraC (100–200 mg/m2), administered by a continuous infusion for 7 days, combined with daunorubicin, administered intravenously for 3 days (the 3+7 induction regimen). This therapy has been reported to induce a complete remission (CR) in 65% to 75% of patients aged 18 to 60 years. This approach results in a long-term disease-free survival of ~30%, with a treatment-related mortality (ie, the percentage of patients who died during induction) of 5% to 10%.
In an effort to improve outcomes of induction therapy, some trials have included alternative anthracyclines or anthracenodiones, incorporated high-dose AraC (HDAraC), or added other agents such as purine nucleoside analogues (PNA), etoposide, fludarabine, or cladribine. However, presently there is no conclusive evidence to recommend one 3+7 induction regimen over another. However, the results of these studies clearly support the claim that further intensification of the induction regimen is not associated with an increased complete remission (CR) rate.
Despite substantial progress in the treatment of newly diagnosed AML, 20% to 40% of patients do not achieve remission with the standard induction chemotherapy, and 50% to 70% of first CR patients are expected to relapse within three years. The optimum strategy at the time of relapse, or for patients with the resistant disease, remains uncertain.
Stem cell transplantation has been established as the most effective form of therapy in patients with AML in first or subsequent remission. Unfortunately, not everyone is a candidate for stem cell transplantation therapy. Doctors are using molecular markers from the cancer cells to help define potential treatment options for additional subgroups of AML patients. Despite the fact that researchers have now defined more 30 AML subtypes of AML, this approach has yet to show any overall survival benefit.
Consolidation therapy comprises treatment with additional courses of intensive chemotherapy after the patient has achieved a CR, usually with higher doses of the same drugs as were used during the induction period. The median disease-free survival for patients who received only the induction therapy is four to eight months. However, 35% to 50% of adults aged <60 years who receive consolidation treatment survive 2 to 3 years. High-dose AraC (2–3 g/m2) is now a standard consolidation therapy for patients aged <60 years.
Maintenance therapy, which is considered to suppress bone marrow activity less than the induction and consolidation forms of treatment, is used in patients who have previously obtained clinical remission. It is a strategy to further reduce the number of residual leukemic cells and prevent a relapse. However, its role in the routine management of AML patients is controversial and depends mainly on the intensity of the induction and consolidation therapies.
How Successful is the Conventional Approach?
Despite the substantial progress in the treatment of newly diagnosed AML, 20% to 40% of patients still do not achieve remission with standard induction chemotherapy, and 50% to 70% of first clinical remission patients are expected to relapse over 3 years.
The prognosis for patients with AML who do not respond to first-line treatment or in those who relapse is generally poor, and optimum strategy at the time of relapse or for patients with resistant disease remains uncertain. Use of stem cell transplantation may be curative for a minority of patients who achieve a second CR and who have an available donor. There is no single regimen or approach that is considered the standard of care in relapsed and refractory AML.
What are People to Do?
The more risk factors people can eliminate from their lives the better. If you are being exposed to benzene or other toxic chemicals known to cause cancer, seek ways to remove them from your life. Radon gas is more common in certain areas than others. Testing for radon gas is easy and if there are toxic levels in your home steps can be taken to eliminate the risk. If you’ve been diagnosed with AML or MDS, working with a conventional oncologist along with a naturopathic or medical doctor board certified in integrative oncology will give you a wide range of evidence-based options. And following a balanced lifestyle with stress reduction, eating an immune-boosting whole foods diet and getting healthy sleep and exercise can promote your immune system and overall health and are important components of a holistic approach.
Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447. [Article] Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007. Blood. 2012;119(1):34-43. [Article] Estey E, Dohner H. Acute myeloid leukaemia. Lancet. 2006;368(9550):1894-1907. [Article] Evrard, AS, Hemon, D, Billon, S et al. Childhood leukemia incidence and exposure to indoor radon, terrestrial and cosmic gamma radiation. Health Phys. 2006;90:569–579. [Article] Giles FJ, Koeffler HP. Secondary myelodysplastic syndromes and leukemias. Current opinion in hematology. 1994;1(4):256-260. [Article] Hake CR, Graubert TA, Fenske TS. Does autologous transplantation directly increase the risk of secondary leukemia in lymphoma patients? Bone marrow transplantation. 2007;39(2):59-70. [Article] Howlader N NA, Krapcho M, Miller D, Bishop K, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA, ed SEER Cancer Statistics Review, 1975-2014. based on November 2016 SEER data submission, posted to the SEER web site, April 2017. Bethesda, MD: National Cancer Institute. [Report] Jabbour EJ, Estey E, Kantarjian HM. Adult acute myeloid leukemia. Mayo Clin Proc. 2006;81(2):247-260. [Article] Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2003:82-101. [Article] Mato AR, Morgans A, Luger SM. Novel strategies for relapsed and refractory acute myeloid leukemia. Current opinion in hematology. 2008;15(2):108-114. [Article]
O’Donnell MR, Tallman MS, Abboud CN, et al. Acute Myeloid Leukemia, Version 3.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017;15(7):926-957. [Article] Ravandi F, Burnett AK, Agura ED, Kantarjian HM. Progress in the treatment of acute myeloid leukemia. Cancer. 2007;110(9):1900-1910. [Article] Robak T, Wierzbowska A. Current and emerging therapies for acute myeloid leukemia. Clin Ther. 2009;31 Pt 2:2349-2370. [Article] Robak T, Wrzesien-Kus A. The search for optimal treatment in relapsed and refractory acute myeloid leukemia. Leuk Lymphoma. 2002;43(2):281-291. [Article] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. [Article] Smith MA, Rubinstein L, Anderson JR, et al. Secondary leukemia or myelodysplastic syndrome after treatment with epipodophyllotoxins. J Clin Oncol. 1999;17(2):569-577. [Article] Smith SM, Le Beau MM, Huo D, et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood. 2003;102(1):43-52. [Article] Takeyama K, Seto M, Uike N, et al. Therapy-related leukemia and myelodysplastic syndrome: a large-scale Japanese study of clinical and cytogenetic features as well as prognostic factors. Int J Hematol. 2000;71(2):144-152. [Article] Tallman MS, Gilliland DG, Rowe JM. Drug therapy for acute myeloid leukemia. Blood. 2005;106(4):1154-1163. [Article] Valentini CG, Fianchi L, Voso MT, Caira M, Leone G, Pagano L. Incidence of acute myeloid leukemia after breast cancer. Mediterr J Hematol Infect Dis. 2011;3(1):e2011069. [Article] Zhu X, Ma Y, Liu D. Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. Journal of Hematology & Oncology. 2010;3(1):17. [Article]
Lab testing is part of many doctors’ appointment. The complete blood count (CBC) is a routine blood test that healthcare providers order on annual exams and as a general screening test for anemia.
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