ACUTE MYELOID LEUKEMIA (AML) Archives

Acute myeloid leukemia (AML) is a fast-growing form of cancer of the blood and bone marrow. AML is the most common type of acute leukemia and occurs when the bone marrow begins to make blasts, cells that have not yet completely matured. These blasts normally develop into white blood cells, but AML, these cells do not develop and are unable to ward off infections.

In AML, the bone marrow may also make abnormal red blood cells and platelets. The number of these abnormal cells increases rapidly, and the abnormal cells begin to crowd out the normal white blood cells, red blood cells and platelets that the body needs.

How Leukemia is Diagnosed

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Introduction to Leukemia

Cancer and neoplastic lesions are affecting our lives every day. Nearly 40% of the world’s population is affected by cancer—irrespective of age, gender, and ethnicity. Equally detrimental to cancer’s physical manifestations are the psychological influences. However, medical advancement and new research are helping to to combat this life-threatening disease.

Of all the cancers of the body, the most treacherous is Leukemia. It is a cancer of blood cells. Humans have three kinds of blood cells: red blood cells, white blood cells, and platelets. Leukemia involves the malignant proliferation of white blood cells (WBC).

Our white blood cells are major components of our body’s defense mechanism. They play a vital role in fighting against diseases, whether bacterial, viral or fungal in nature. They originate within the bone marrow, spleen and lymph nodes.

A person suffering from Leukemia has poor white blood cell functioning. WBCs start to divide abnormally eventually outgrowing the normal number of cells.

Leukemia has 4 types:

  1. Acute Myelogenous Leukemia (AML)
  2. Chronic Myelogenous Leukemia (CML)
  3. Acute Lymphocytic Leukemia (ACL)
  4. Chronic Lymphocytic Leukemia (CLL)

1. Acute Myelogenous Leukemia (AML)

Acute Myelogenous Leukemia is a heterogeneous clonal disorder. It is characterized by immature myeloid cells and bone marrow failure. It commonly affects children and adults. Studies have suggested the disease arises from recurrent hematopoietic stem cell genetic alterations.

2. Chronic Myelogenous Leukemia (CML)

Chronic Myeloid Leukemia is a myeloproliferative (slow-growing blood cancer) disorder characterized by the existence of a balanced genetic translocation of chromosomes 22 and 9. It mostly affects adults. CML consists of 3 distinct phases: chronic, accelerated, and blast phases.

The history of patients with CML shows 3-5 years of chronic stage proceeding to a fatal blast phase and then progressing to an accelerated phase.

3. Acute Lymphocytic Leukemia (ALL)

Acute Lymphocytic Leukemia is the second most common Leukemia occurring in adults. Like other Leukemias, ALL’s pathophysiology is also based on chromosomal abnormalities and genetic alterations which happen to take place in differentiation and proliferation of lymphoid precursor cells present in the bone marrow and blood. In adults, the precursors of B- lymphocytes are greater in number than the malignant T- lymphocytes.

4. Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia is a tumor of CD5+ B cells that characterizes the deposition of tiny, mature lymphocytes in the blood, bone marrow and lymphoid tissues. Apart from the CD5 cells, other genetic alterations are involved in the pathogenesis of Chronic Lymphocytic Leukemia. Stromal cells, T cells and nurse-like cells in the lymph nodes also predominate.

Causes and risk factors for Leukemia

Although the exact cause of Leukemia is unknown, certain risk factors can contribute to making a person susceptible to it. These include radiation, viruses, exposure to benzene, smoking, genetics, and family history.

1. Ionizing radiations

Exposure to ionizing radiation comes from continuous radiation therapy for treating any pre-existing cancer. Prolonged exposure to X-rays is found mostly in people who work as radiologists and are exposed to persistent radiation. Patients who have received chemotherapy sessions for cancers are also prone to Leukemia. Ionizing radiations damage the DNA and result in the defective genetic makeup of stem cells.

2. Viruses

The Human T-lymphotropic Virus (HTLV-1) has been shown to have an association with Leukemia.

3. Exposure to benzene

Benzene is a toxic solvent used in cleaning chemicals and some hair dyes. Benzene’s toxic effects on the blood and bone marrow include increasing the risk of Acute Myeloid Leukemia (AML), myelodysplastic syndrome, and other hematological malignancies, such as non-Hodgkin’s lymphoma.

4. Smoking

Smoking is not only detrimental for the lungs alone but for the entire body. Although the link between smoking and Leukemia is unclear, studies say it can affect the bone marrow and increase the chances of AML in young adults.

5. Genetic conditions

Chromosomal abnormalities are also responsible for increasing Leukemia susceptibility. Examples include Down syndrome, Klinefelter syndrome, Fanconi anemia, Li-Fraumeni syndrome, Bloom syndrome, Ataxia-telangiectasia, and neurofibromatosis, to name a few.

6. Hereditary

The most common cause of Leukemia is family history. If any family member has had Leukemia it increases the risk for other blood relatives.

Signs and symptoms of Leukemia

The signs and symptoms of Leukemia vary with different forms. They are generally nonspecific and warrant investigations for proper diagnosis.

Acute Myeloid Leukemia (AML)

The signs and symptoms of AML are:

  • Fever
  • Pain in bones and joints
  • Pale skin
  • Easy bruising and contusions
  • Recurrent infections
  • Unusual bleeding, epistaxis, bleeding gums

Chronic Myelogenous Leukemia (CML)

The signs and symptoms of CML are:

  • Fatigue and muscle weakness
  • Shortness of breath
  • Pyrexia
  • Increased sweating mostly during the night
  • Cachexia (weight loss)
  • Abdominal discomfort secondary to spleen enlargement
  • Stomach bloating
  • Itching
  • Pain in joints and bone

Acute Lymphocytic Leukemia (ALL)

The signs and symptoms of ALL are:

  • Joint pain and muscle fatigue
  • Fever
  • Frequent infections
  • Epistaxis (Nose bleed)
  • Lumps felt around the neck, groin and underarms as a result of lymph node swelling.
  • Pale skin
  • Shortness of breath

Chronic Lymphocytic Leukemia (CLL)

The signs and symptoms of CLL are:

  • Nocturnal sweating
  • Fever
  • Recurrent infections
  • Fatigue and constant tiredness
  • Cachexia
  • Loss of appetite
  • Stomach bloating as a result of splenomegaly (enlarged spleen)
  • Shortness of breath
  • Pea-sized swelling or lumps in groin, neck or armpits.

Diagnosis of Leukemia

Early detection can prevent complications. The earlier the diagnosis the easier treatment is. Medical advancement has made diagnosis easier than ever before. Some of the essentials to reach an accurate and precise diagnosis are enlisted below.

History and examination

A proper and detailed history is the key to an ideal diagnosis. It involves asking relevant questions related to the signs and symptoms that can link to the suspected disease.

Your physician might ask the following questions:

  1. How long have you been feeling a fever?
  2. What is the temperature?
  3. Do you feel a loss of appetite?
  4. Have you experienced prolonged bleeding after a cut?
  5. Have you noticed any changes in weight recently?
  6. When did you notice lumps?
  7. Are these lumps felt, painful and movable?
  8. Did you feel the lumps gradually increasing in size?
  9. Do you face difficulty in breathing?
  10. Do you feel you sweat a lot while sleeping?
  11. Are you taking any medications?
  12. Have any of your family members had any diseases?
  13. When did you feel the need to visit the physician?

The answer to the above questions can lead to the next step, investigations.

Investigations for Leukemia

Investigations are the major component involved in diagnosis as they make the suspected disease clear to understand. These include blood tests, radiology and biopsy.

1. Blood tests

  • Complete Blood Count (CBC)
  • White Blood Cell (WBC) differential
  • Blood smear
  • Tumor markers
  • Cerebrospinal fluid (CSF) analysis
  • BCR ABL1
  • Genetic tests for targeted cancer therapy
  • Chromosome analysis

The most commonly used test is the Complete Blood Count (CBC) which shows a clear picture of the abnormal growth of red blood cells, white blood cells and platelets.

2. Radiology

The excessive proliferation of the cells in the bone marrow leads to marrow expansion and invasion of the cortex which, in later stages, can be seen by radiographic studies. A simple X-ray can reveal any spot bone changes. In some circumstances, a CT-scan may be needed to extensively study the disease and prognosis.

X-ray findings may include:

  • Osteolytic lesions; most commonly seen in Acute Lymphocytic Leukemia seen in small and flat bones, metaphysis of long bones.
  • Metaphyseal bands (classical Leukemia lines)
  • Bone destruction
  • Some pathological fractures
  • Radiological lesions, in later cases, are seen in the form of vertebral collapse, osteolysis of bones and avascular osteonecrosis.

3. Bone marrow biopsy

This is the gold standard investigation to diagnose Leukemia. This invasive procedure is done after the suspicion of Leukemia or when the blood test reports point to a Leukemic picture.

The procedure involves the removal of a small sample of bone marrow from the hipbone. A long, thin is the needle is used to extract the bone marrow. Once the sample has been taken it is sent to the laboratory where the histopathologists study the tissue microscopically.

Prior to examining the histopathologist or the lab technician prepares a slide. During the process, the specimen is then cut into thin slices. The sectioned structure is dyed using different dyes. The dye discriminates against the parts of the cells. The section is then placed on a glass slide and then covered with a slip on the top to keep the specimen intact. The slide is now ready to be placed under the microscope.

The samples examined under the microscope are then studied based on the type of cells, how the cells are arranged, whether the cells are normal or abnormal etc.

The microscopic findings may reveal:

  • Acute Myeloid Leukemia

Increase in bone marrow cellularity, consisting of granulocytic or monocytic forms a number of erythroid precursors

  • Acute Lymphocytic Leukemia

Hypercellular bone marrow with multiple tightly packed lymphoblasts that have undetectable cytoplasm, round irregular shape, divided nuclei, and dispersed chromatin. The bone marrow has B and T lymphoblasts with indistinguishable morphology along with necrosis in some areas.

Treatment for Leukemia

Treating Leukemia challenges all medical practitioners. Its success and failure solely depend on the extent of the disease and how far has it spread within the body.

Following are treatment options that can help fight Leukemia.

1. Chemotherapy

Chemotherapy is the use of anticancer drugs to kill or halt the proliferation of cancer cells. Generally, chemotherapy is administered orally or intravenously. In some patients, the chemotherapeutic agent is given intrathecally, i.e., injected into the CSF (cerebrospinal fluid) that bathes the brain and spinal cord. This is done after performing a lumbar puncture and injecting chemotherapeutic drugs, such as methotrexate. The course is usually repeated every three weeks.

2. Radiotherapy

Compared to chemotherapy that attacks all the cells of the body, including the healthy ones, radiotherapy is a localized treatment regimen. High ionizing-energy radiation emits to destroy cells that have an increased proliferation rate. Radiotherapy can either be given to cure the disease (therapeutic) or to improve the signs and symptoms encountered during the disease course (palliative).

3. Stem cell or bone marrow transplantation

Transplants are widely used in management and treatment of the disease. Bone marrow is transplanted from a patients’ family member, or another person who bears the same type of bone marrow, into the diseased person. The survival rates vary with different factors but the cost and affordability remain the major concern in this treatment modality.

4. Immune therapy

Immune therapy is another set of treatments that has some promising result in managing Leukemia. The immune therapy works by promoting the immune cells of the body to fight against cancer cells. One of the successful regimens in immune therapy is Gleevec, commonly given in Chronic Myeloid Leukemia. CML patients live a long, symptomless life with the daily oral administration of this drug.

Complications with Leukemia

Though Leukemia is curable, treatments may give rise to certain complications–basically the body’s response to the treatment given. The complications mostly arise from chemo and radiation.

They can include:

  • Anemia
  • Skin rashes
  • Altered taste sensations
  • Soreness of the mouth and throat
  • Liver dysfunction
  • Hair loss
  • Diarrhea
  • Fatigue
  • Bleeding
  • Fertility problems
  • Nausea and vomiting
  • Neurological effects
  • Impaired sexual activity

Relapse of the disease may also occur after some years.

Conclusion

The prognosis of Leukemia depends on how far has the disease has spread but the medical advancement has brought in new regimens that can now treat Leukemia at any stage. A person suffering from Leukemia and undergoing its treatment should be dealt with love, care, and pampering

How to help prevent Leukemia

Informational campaigns and awareness programs help people learn about the risk factors of Leukemia. Family members of Leukemia patients should undergo blood screenings to see if they have been affected. A good diet can help improve health status. Limiting use of benzene-infused chemicals can also make the disease less susceptible. Ceasing tobacco smoking can also help keep Leukemia at bay.

 

References

Acute Lymphoblastic Leukemia

Leukemia: an overview for primary care

Acute Myeloid Leukemia: diagnosis and management based on current molecular genetics approach

Treatment of acute myeloid leukemia

Clonal hematopoiesis and preleukemia-genetics, biology, and clinical implications

No free rides: management of toxicities of novel immunotherapies in ALL, including financial

Adult Acute Myeloid Leukemia Treatment

Acute Lymphocytic Leukemia

Genetics and prognosis of ALL in children vs adults

Etiology of leukemia. A review

Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records

Acute lymphoblastic leukemia: a comprehensive review and 2017 update

Acute myeloid leukaemia: optimal management and recent developments

Overall Health and Mindfulness Improves Treatment Response: An Expert Explains

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Dr. Sangmin Lee shares the benefits of meditation and yoga and explains how mindfulness can affect your overall health.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital.

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Transcript:

Patricia:

How about this one? A positive attitude and mindfulness can improve treatment response.

Dr. Lee:

Absolutely. Absolutely. Treatment for leukemia can be tough. Some of the treatment involves intense chemotherapy. Treatment for leukemia can involve stem cell transplant. And a key important aspect of treatment is being healthy and being optimistic about treatment, because a lot of treatment can have side effects, and side effects can be not as apparent if you are physically more active, and in a good state. So, I think that having a positive outlook is very, very important.

Patricia:

Quality of life issues are difficult for some people. How do you talk with your patients about their quality of life, and staying healthy during their treatment?

Dr. Lee:

So, quality of life is absolutely important. I mean, the whole point of treating leukemia and any other treatment is not only to address the leukemia, but also have good quality of life. So, when discussing treatment options, you always have to balance the quality of life and side effects versus potential benefits. So, that’s always on our mind when discussing potential treatment options, and how it impacts the quality of life. Throughout the treatment process, we always tell our patients that being active, and having a good quality of life, and having good nutrition, is absolutely important, because that’s a key aspect of treatment for leukemia.

Patricia:

What about meditation and yoga for coping with anxiety around cancer diagnosis and treatment? Mindfulness.

Dr. Lee:

Absolutely, absolutely. Those can help. Especially having leukemia, it’s very life-changing, so a typical way that patients are diagnosed with acute leukemia is patients live a normal life, and then they develop, all of a sudden, abnormalities. And they’re diagnosed with acute leukemia, and it can be very sudden. And it can be very difficult. So, that can understandably make patients have anxiety, and other issues.

And I believe that meditation, and yoga, and other exercises can absolutely help cope with this.

Patricia:

And there’s tons of resources for meditation and yoga out there, that are reliable.

Dr. Lee:

Yes. Yeah.

Patricia:

Yeah. Should patients regard yoga and meditation as part of their treatment, as part of their self-care, during this process?

Dr. Lee:

Absolutely, absolutely, if the patients are into meditation and yoga. Meditation is very harmless, and it can absolutely help in terms of guiding their mind through their treatment journey. Yoga is good if you’re physically able to do it. So, one caution is that, if you’re not someone who does yoga normally, then you should start off slow, and not push yourself as aggressively.

Does Cannabis Oil Have a Role in Cancer Treatment?

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Is it just a trend or could cannabis oil truly have a role in cancer care and treatment? Dr. Sangmin Lee share his perspective.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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Transcript:

Patricia:

The use of cannabis oil is becoming prevalent. Does this have a role in cancer care and treatment?

Dr. Lee:

Absolutely. So, we use it for a lot of side effect management. So, cannabis can be helpful, in terms of appetite and nausea, for example. So, we often use it in conjunction to manage some of the side effects that patients can have throughout their treatment.

You should consult with your medical team, and of course, I should say that laws differ state by state, so it doesn’t apply to every state. But when it’s available, it can be a valuable addition.

Patricia:

Sure. Discuss that with your physician.

Sugar Feeds Cancer: Fact or Fiction?

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Does sugar feed cancer? Dr. Sangmin Lee addresses the rumored connection between sugar and cancer.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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Transcript:

Patricia:

Okay, a little more fact or fiction, here. This is what we’ve heard from patients who have AML about cures, okay? Sugar feeds cancer, and severely restricting my diet will treat my AML.

Dr. Lee:

That’s not proven so far. There are some laboratory studies, especially with keto diets, showing some promise, maybe. But then it hasn’t been proven in humans, yet. The most important thing about AML treatment is actually nutrition. As patients go through AML treatment, it’s very important to stay healthy, and part of that is nutrition.

So, starvation, in general, is not recommended, because nutrition is so important, in terms of being able to undergo the treatment, as well as treatment visits, and everything. So, we recommend that nutrition is very important.

Are Clinical Trial Participants Monitored More Closely?

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Dr. Sangmin Lee discusses the monitoring of clinical trial participants and the measures taken for patient safety.

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Transcript:

Patricia:

How about this next one? I am monitored more closely in a clinical trial.

Dr. Lee:

In some cases, it’s true. Clinical trials do have certain monitoring visits, in terms of doctor’s visits, laboratory tests, and physical exams.

The purpose of that is to make sure that it is safe. So, the purpose of monitoring closely, in a lot of cases, is for the patient’s safety. We are testing drugs in a lot of clinical trials, for which the complete safety profile, as well as efficacy profile, is not known. So, the purpose of closer monitoring is to make sure whatever we’re doing is safe, and if there are any unexpected side effects, then it allows us to address the side effects, as well. So, it’s mainly for patients’ safety.

Will Clinical Trials Cost You? The Facts.

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Dr. Sangmin Lee reviews the financial impact associated with clinical trials, including a discussion of what expenses are covered for participants.

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Transcript:

Patricia:

All right, how about this one: I may have unexpected costs if I join a clinical trial.

Dr. Lee:

So, typically, that’s actually, usually not true, because how it works is that the clinical trial drugs, and that there may be extra procedures or visits associated with clinical trials.

And what usually happens is that the sponsor of the clinical trial provides the cost of the drug, intervention, and anything extra that are required for the clinical trial. So, in the end, the cost of participating in a clinical trial should not be any more than receiving standard care treatment.

In some rare cases, there may be stipends associated with the clinical trial, especially with travel. So, if you participate in a clinical trial, and you live far away, then you should ask to see if there is any stipends available, especially for travel.

The Truth About Clinical Trials in AML

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Dr. Sangmin Lee reviews common misconceptions about clinical trials and shares examples of how these studies are changing the landscape of AML treatment. Want to learn more? Download the Program Resource Guide here.

Dr. Sangmin Lee is a hematologist-oncologist specializing in blood disorders and blood cancers at Weill Cornell Medicine and New York Presbyterian Hospital. 

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Transcript:

Patricia:                      

I’ll tell you a few things that we’ve heard from AML patients, and you tell me if this is fact or fiction. Okay, Dr. Lee?

Dr. Lee:

Yeah.

Patricia:

Clinical trials are the last resort treatment option.

Dr. Lee:

That’s actually not true in a lot of cases, because, yes, there are a lot of clinical trials after you have tried all of the standard therapy. But then, standard therapy in AML, like any other condition, are not perfect. So, there are many clinical trials where, even if you’re diagnosed with new AML, because standard care is not perfect, there are trials to try to improve upon the standard of care.

So, there may be clinical trials when you’re first diagnosed with AML, as well.

Patricia:

Yeah. How about this one: I feel like a guinea pig.

Dr. Lee:

Well, the clinical trial is to test drugs in humans. So, in a way, you are a test subject. But then, you have to remember that all of the drugs that we are testing have a rationale.

They all show promise, in terms of laboratory testing to kill leukemia cells in the test tube. And the problem is that, just because they are killed leukemia cells in the test tube, or in an animal model, doesn’t actually mean that it works in humans, or we know the safety profile. So, we need to do these testings to demonstrate that these drugs, which seem promising, actually work in humans.

Patricia:

Right. Well, then, that’s a good segue to this thing we’ve heard: Treatments being studied today may be the future standard of care.

Dr. Lee:

That is absolutely true, because all of the new developments that have come out, including Venetoclax, or IDH inhibitors, or other inhibitors, that are approved today, came through the clinical trial process. One example I like to include is a patient of mine, who, five years ago, had very, very aggressive leukemia, and she happened to have an IDH2 mutation.

It was four or five years ago. And she has a very refractory, aggressive leukemia, and it was life-threatening. And she had an IDH2 mutation. And we enrolled her in a clinical trial involving ivosidenib, which was in clinical trial at the time.

Ever since then, she became – she went into remission, and she has a normal blood count. And, to this day, she’s on this medicine, which is now approved, and she remains healthy with a normal blood count, in remission. So, yes. Clinical trials do include promising drugs, and if they show really good efficacy and promise, they will become standard of care down the road.

The advantage of clinical trial is that you may get early access to drugs that may become standard care down the road. So, it’s a way to get early access to potentially promising drugs.

Patricia:                      

How do you counsel your patients about joining clinical trials? What are you thinking about when you’re talking with them?

Dr. Lee:                       

So, in terms of clinical trials, we all look at clinical trials, and they exist for a reason, because we think that an intervention or drug can do better than standard of care. So, how I approach it is that, depending on the situation, if we can improve upon what is available, or if there are no other options, then it definitely is a great option to improve upon what would otherwise be standard.

Patricia:                      

I’ve got one more. Once I enroll, I am locked into the trial, and I can’t change course.

Dr. Lee: 

Absolutely not true. So, clinical trial participation is always voluntary. So, if you sign a clinical – So, what happens is you typically sign a consent to participate in a clinical trial.

And if you change your mind at any time, you can decide not to participate in a clinical trial. It’s not a binding agreement, so you can decide not to participate at any time.

Patricia:

Great. And that’s obviously a decision you should make with your healthcare provider before withdrawing.

Dr. Lee: 

Oh, absolutely. Absolutely, absolutely. But you should always remember that just because you sign up for a clinical trial, it’s not a binding requirement to stay on it.

Patricia:                      

Okay, okay. And let’s talk for just one moment, if you have a second again, about why patients – why it’s important for patients to participate in clinical trials.

Dr. Lee:                       

Why it’s important? It’s because the drugs we test could become the standard care in a few years. And you might have early access to a promising drug that may change treatment of AML. One prime example is Venetoclax. Venetoclax, when it was in clinical trial, was very promising, but before we started treatment, we had no idea how well it was going to work.

So, the patients receiving Venetoclax obviously benefitted from it, and they had early access to a drug that would have become standard of care a few years down the road.

Is It Safe? Breaking Down the Clinical Trial Process

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The idea of a clinical trial can be intimidating and confusing for many patients. Dr. Sangmin Lee explains the phases of clinical trials, including the safety protocols in place to protect patients.

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Transcript:

Patricia:

What is the process for getting medicine to patients during clinical trials?

Dr. Lee:

So, clinical trials are basically what’s needed to prove that drugs work. So, a lot of times, we test drugs in a test tube in AML cell lines, and they show great promise. But just because a drug works in a test tube setting, doesn’t actually mean that it will work in humans, because human bodies are much more complicated. So, we need to test promising drugs in humans to make sure they are safe and effective.

And that’s what the purpose of clinical trials are. Once they demonstrate safety and efficacy, then a drug then gets to be approved, and is available commercially. So, that’s the purpose of clinical trials.

To be involved in clinical trials, what it involves is, basically, you have to meet a sort of criteria, called eligibility, because different clinical trials have different criteria for selection. So, we have to look into that. And then, once you fit an eligibility or selection criteria, then you typically undergo certain diagnostic tests to enroll on a clinical study. And then, you get whatever drug or intervention that is designed to test in that setting.

So, there are numerous steps to actually enroll in a clinical study.

Patricia:

And like you mentioned, there’s a long way between rat studies and human trials. What are the phases of clinical trials?

Dr. Lee:

So, there are three phases for clinical trials, commonly. There’s phase one, and phase two, and phase three. Phase one is the earliest part of the clinical trial process. So, goal of a phase one study is to make sure a drug is safe in a human. So, phase one studies are usually the first time that you are testing the drug in humans, and the main purpose is to demonstrate that it’s safe. So, typically, in a phase one study, typically, you test a drug at a lower dose or dose levels to demonstrate safety. What it means is that you’re enrolling a few patients at a time.

Once a drug is proven to be safe, then you move on to phase two, which is basically testing the drug in more patients. And the purpose of phase two is to get a preliminary assessment of how effective a treatment would be.

So, typically, a phase two study involves many more patients in that setting. And then, if a phase two study shows that a drug is very promising, then the drug may move on to phase three, where, basically, in phrase three, you are comparing one intervention or a drug compared to the standard of care. And, typically, in a phase three setting, a computer decides randomly which intervention you get, whether it’s an intervention or new drug versus standard of care. And standard of care may include either placebo or chemotherapy intervention, that is standard of care. So, it’s not always placebo in phase three.

AML Treatment Advances: What’s New for YOU?

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 AML specialist and researcher, Dr. Sangmin Lee, breaks down the recent advances in AML treatment and how targeted therapies are improving patient care.

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Transcript:

Patricia:

Dr. Lee, thanks so much for joining us, again. Can you please give us an overview of the field of AML research?

Dr. Lee:

So, AML research is evolving very rapidly, and there’s a lot of promising new drugs that have come out in AML. As with any other cancers, we’re getting more sophisticated in characterizing AML in terms of molecular mutations, and characterizing AML stem cells, so –

The field is moving very rapidly in that regard. There have been a number of promising and effective drugs that have been approved in the last few years, as well. For example, Venetoclax has been a game changer in treatment of AML, especially in the elderly population. And there are several targeted agents that have been FDA approved in the recent years, as well. So, definitely since about three to five years ago, there have been new drugs that have come out for AML that is very exciting for treatment of AML.

Patricia:

Let’s talk a little bit about genetic testing. How is that changing the landscape for AML patients?

Dr. Lee:

So, genetic testing has become standard in AML patients, in terms of – at their diagnosis and relapse. And part of that is, we can use that information to guide prognosis, how well or not well a patient is expected to do.

But more importantly, there are actually drugs that can target specific mutations. For example, there are new drugs that target a mutation called IDH1 and 2 that have been approved recently for patients with AML, as well as new drugs that target mutation called FLT-3, or FLT3 mutation, as well. So, genetic testing has become standard, not only to tell you prognostic information, but also used in therapy for AML patients.

Patricia:

You mentioned a few treatments that were advancing. What other therapies are showing promise for AML?

Dr. Lee:

So, there are a number of treatments that are ongoing. Venetoclax has been game-changing, and now, although Venetoclax has improved outlook, in terms of AML treatment, compared to conventional therapy, there’s still resistance to Venetoclax and the response is not durable.

So, there is research looking at resistance mechanisms to Venetoclax, for example. The other exciting field is, there are some advances in immunotherapy, with clinical trials underway. Like in other malignancies, there are clinical trials involving CAR T-cell, or other ways of engaging your own T cell immune system to approach and attack the AML.

AML Research: What’s New in Treatment?

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 AML expert, Dr. Jessica Altman, discusses the future of AML research, and new learnings that continue to improve current treatment approaches.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about Dr. Altman here.

See More From The Fact or Fiction? AML Series

Related Resources

Misconceptions in Clinical Trials: What’s Fact and What Fiction?

AML Treatment Options: What’s Available?

AML Treatment Treatment Side Effects: What’s Fact and What’s Fiction?

Transcript:

Patricia:            

Are there any new treatments on the horizon that you can talk about, Dr. Altman?

Dr. Altman: 

Absolutely. So, I love to talk about new therapies in AML. Until the last couple of years – it had been 40 years since we approved a sustained treatment in the marketplace in AML. We had been treating the disease the same. And over the last couple of years there have been a growth of therapies. We’re now trying to sort out exactly when we’re using one over another. We also have clinical trials where we’re combining novel therapies for adults with either newly diagnosed disease or relapsed and refractory disease. 

We are in an era of looking out at antibody therapy in AML – that’s one of the new waves of treatment. We are still exploring targeting therapies in the sense of inhibition of FLT3, IDH, and other mutations. So, it’s an era where there’s lots of excitement, and I’m hopeful for our patients.

Patricia:     

Yeah. Tell me what makes you most hopeful about the future of research in this area, and treatment?

Dr. Altman: 

So, I think that’s a great question. I think the fact that we now – the deeper the understanding we have of the biology of the AML, why AML happens, what mutations drive the disease, and then how to target those mutations with individual therapies is what excites me the most. So, our basic science research has exploded, and that occurs at a very quick pace, and that’s allowing us to develop therapies at a much faster rate than I would have anticipated before.

Patricia:

What a wonderful way to end our chat. Thank you so much, Dr. Altman, for taking the time to join us today.

Dr. Altman: 

It’s a pleasure to be here. Thank you so much.

Misconceptions in Clinical Trials: What’s Fact and What’s Fiction?

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AML expert, Dr. Jessica Altman, addresses common misconceptions patients have about clinical trials regarding treatments, regulations, and standards of care. Want to learn more? Download the Program Resource Guide here.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about Dr. Altman here.

See More From The Fact or Fiction? AML Series

Related Resources

 

How Is an AML Treatment Approach Determined?

  

Understanding and Managing AML Treatment Side Effects

  

Addressing Common Myths About AML Treatment

Transcript:

Patricia:            

What about clinical trials? What common misconceptions do patients have about enrolling in trials?

Dr. Altman: 

So, I think the misconceptions regarding clinical trials can be very masked. And I think it really depends on the intent of a clinical trial and the phase of the clinical trial. I think that a well-designed clinical trial is almost always the right choice for a patient with acute leukemia at any stage in their therapy. 

That is a bias as a clinical trialist. I think it’s the right bias, but it is still my bias. I think patients frequently worry that they’re being treated as a guinea pig, or they’re not getting an appropriate treatment. What I can tell you is the clinical trials that we and my colleagues across the country and across the world participate in are clinical trials where the patients are getting at least what we consider a standard of care for that phase of their disease, and they may be getting something in addition to that or something that is slightly different, but expected to have a similar response rate. 

We have this phrase in clinical trials, something called equipoise, that if there’s a randomization between options that we need to feel, as the practitioner and as the clinical trialist, that each option is at least as good as the other.  

Patricia:

That kind of goes back to the vetting of treatments before they go to a clinical trial. Tell me a little bit about history. How can we make patients feel more comfortable?

Dr. Altman: 

I want to make sure that I understand the question.

Patricia:

So, how thoroughly are treatments vetted before they go to a clinical trial?

Dr. Altman: 

Great. So, the way that agents get into early phase clinical trials and then later phase studies are these are compounds that have been studied in the laboratory, then studied in small animals, then larger animals. And then, frequently, a drug is started in a patient with relapsed and refractory Acute Myeloid Leukemia and found to be safe – that’s what we call a Phase I study. 

Once we know the right dose and the associated side effects from an early phase clinical trial, later phase studies – i.e. Phase II, where the goal is to determine the efficacy and response rate is conducted. And then, if that appears and looks like it’s promising, a larger, randomized, three-phase study is frequently conducted, where we compare a standard of care to the new approach. 

Patricia:

So, patients should be comfortable that the clinical trial that they’re going through has been thoroughly vetted, has gone through multiple stages before human trials occur?

Dr. Altman: 

That is accurate in terms of compounds get through animal studies, and then depending on the way that the trial is being connected, will then be studied in patients either with relapsed or refractory disease or very high-risk disease. But it’s also very important to mention that these pharmaceutical companies and physicians are not making these decisions alone. 

The clinical trials are all reviewed by scientific review committees through the cancer centers, which are other investigators making sure that everything appears appropriate. In addition, there are institutional review boards at every university whose goal it is to keep patients and research subjects in well-done clinical trials safe. That is their primary goal. And the IRBs – institutional review boards – are very involved with making sure that clinical trials are appropriate and that the conduct of clinical trials is appropriate.

Addressing Common Myths About AML Treatment

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AML expert, Dr. Jessica Altman, discusses common myths surrounding available AML treatment options, stem cell transplant and how leukemias are classified.

Dr. Jessica Altman is Director of the Acute Leukemia Program at Robert H. Lurie Comprehensive Cancer Center of Northwestern University. More about Dr. Altman here.

See More From The Fact or Fiction? AML Series

Related Resources

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AML Treatment and Side Effects Program Resource Guide

Transcript:

Patricia:            

Dr. Altman, let’s talk about some AML treatment myths floating around. I’ll throw some stuff out there, you let me know if you’ve heard this. “Leukemia is one disease.”

Dr. Altman: 

So, I have heard that. Leukemia is actually a number of different diseases, and it’s very heterogenous. There are acute and chronic leukemias. The acute versus chronic really depends on a couple of factors. The biologic factor is the presence or absence of 20% loss or more in the bone marrow, but that also coincides with how patients present clinically. Acute leukemias tend to present more acutely, more rapidly. And chronic leukemias tend to be a bit more indirect. And the treatments are very different for those entities. 

There are also myeloid or lymphoid leukemias, so there’s Chronic Myeloid Leukemia and Acute Myeloid Leukemia and Chronic Lymphocytic Leukemia and Acute Lymphoblastic Leukemia. So, those are the four major categories. We’re talking about Acute Myeloid Leukemia today. Within Acute Myeloid Leukemia, there are multiple different types of Acute Myeloid Leukemia that are really now best categorized by history – patient history – and the molecular and cytogenetic abnormalities of the disease. 

Patricia:

Now, we’ve already learned about a bunch of them. So, “There are limited treatment options” is definitely a myth. Correct, Dr. Altman?

Dr. Altman: 

So, we have had a major growth of the number of treatment options available for Acute Myeloid Leukemia really in the last couple of years. It’s been a very exciting time for practitioners and for our patients that we have now a number of new therapies. So, there is not just one treatment available. In fact, the conversation regarding treatment options becomes quite extensive with patients and their families, because there are choices. And that’s why consideration of goals in the intent of treatment becomes even more important. 

Patricia:

Here’s another one: “Stem cell transplant – the only chance for cure.”

  Stem Cell Transplant, also called a bone marrow transplant, is a procedure in which healthy blood stem cells are used to replace damaged or diseased bone marrow. This procedure can be used to treat certain types of blood cancers.

Dr. Altman: 

Okay. So, that is also a myth. There are certain types of Acute Myeloid Leukemia where stem cell transplant is the most appropriate treatment once the disease is in remission if the goal of the patient is of curative intent. Stem cell transplant is not appropriate for every individual, and for some types of Acute Myeloid Leukemia, stem cell transplant is not considered. 

Patricia:

What kinds of things do you think about when you’re considering a stem cell transplant with a patient? 

Dr. Altman: 

So, again, I go back to patient goals and understanding their goals of treatment. A stem cell transplant is among the most medically intensive procedures that we have. It is also not just a treatment that occurs over a short time. While the actual transplant is a relatively limited hospitalization and the administration and infusion of stem cells and preparative chemotherapy, it is something that can continue to have side effects and alterations in life quality that can persist for months to years afterwards. 

So, that’s one aspect of things that we talk about regarding stem cell transplant. And really understanding what the benefit of transplant is in terms of a survival advantage, versus what the risk and the cost in terms of toxicities are. And that’s the basis of a lot of the conversations we have.

Patricia:

Sure. Here’s one more: “AML patients require immediate treatment.”

Dr. Altman: 

Sometimes AML patients require immediate treatment, and sometimes they don’t. And that depends on the biology of the disease. How high is the white blood count when the patient comes in? What are the best of the blood counts? Is the patient having immediate life-threatening complications of their acute leukemia? 

And there’s some forms of acute leukemia that require immediate therapy to prevent complications, and there’s some forms of acute leukemia who present an extreme distress from their disease, but there are many patients who present with acute leukemia, and we have time to get all of the ancillary studies back – the studies of genetics and the molecular studies1 – to help further refine the conversation, and further design an appropriate treatment strategy. 

Patricia:

What else? What do you hear from your patients that you feel is maybe a misconception or something they’re not quite understanding about the AML?

Dr. Altman: 

So, I think one of the biggest things that I would like to mention is that response rate and cure are not the same. So, it is possible for one to be treated for Acute Myeloid Leukemia and the disease to enter remission, and yet still not be cured of their disease. 

Acute Myeloid Leukemia is a disease that frequently requires additional cycles of treatment or a stem cell transplant after the initial induction therapy to be able to have the best chance for a long-term cure. So, response and cure are not the same thing.

Acute Myeloid Leukemia: Your AML, Your Treatment, Your Decision

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Acute Myeloid Leukemia: Your AML, Your Treatment, Your Decision from Patient Empowerment Network on Vimeo.

AML experts Dr. Pinkal Desai, Assistant Professor of Medicine at Weill Cornell Medical College and Assistant Attending Physician at the New York-Presbyterian Hospital, and Dr. Tapan M. Kadia Associate Professor, Department of Leukemia at The University of Texas MD Anderson Cancer Center, share research-based insight on how AML is diagnosed, including the symptoms and recommended tests, and disease management strategies.
 
These experts give an overview of currently approved AML therapies and share clinical trial updates on treatments in development. The panel discusses AML management and how you can ask questions and talk to your doctor to feel confident with your care. Additionally, you will hear from an AML patient who shares their experience and advice for approaching the decision-making process.
 

What is Acute Myeloid Leukemia?

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Introduction to Acute Myeloid Leukemia

If you have been diagnosed with Acute Myeloid Leukemia, or someone close to your heart has been, you may be understandably concerned or fretful. Regardless of the type or where it appears in the body, cancer is one of the greatest causes of concern.

Cancer is the accumulation of abnormally proliferating cells that form an abnormally growing mass called a tumor. The cancer cells in a tumor grow and divide rapidly and are no more under regulation by the normal signaling mechanism.

Typically, cancer may be either benign or malignant. Benign cancer cells remain confined to the area of origin (such as a skin wart). Malignant cancer means the unregulated cells invade the surrounding structures and eventually spread throughout the body via the circulatory or lymphatic system. Eventually, malignant cancer compresses vital structures and compromises their functions.

What is Acute Myeloid Leukemia?

Acute Myeloid Leukemia (AML) is a cancer of the blood and bone marrow, as suggested by the term Leukemia. Bone marrow is the spongy tissue within the bone where blood cells are produced.

In this cancer, too many immature white blood cells form and interfere with normal blood cells. AML affects myeloid cells, a group of blood-forming progenitor cells that mature into various blood cells such as Erythrocytes (red blood cells that supply oxygen, the platelets that clot blood after an injury), Monocytes, Basophils, Macrophages, and more.

AML is a malignant blood cancer. It is referred to as “acute” because the condition progresses rapidly.

You might hear your doctor refer your condition with names other than AML. Don’t get confused if your healthcare practitioner refers to it with the following names—all secondary terms for the same condition, Acute Myeloid Leukemia:

  • Acute myelogenous leukemia
  • Acute myelocytic leukemia
  • Acute granulocytic leukemia
  • Acute non-lymphocytic leukemia

The 5-year survival rate of AML is approximately 24% for people over 20 and about 10-15% in patients age 60 years and above. For people younger than 20, the 5-year survival rate is about 67%. Once diagnosed with AML, seek treatment as soon as possible because this is a rapidly deteriorating condition that spreads quickly to other parts of the body such as:

  • Spleen
  • Lymph nodes
  • Liver
  • Brain and spinal cord
  • Testicles

Now that you’ve understood what AML is, let’s talk about what causes AML, the symptoms associated with it, its treatment and post-treatment effects.

Causes and risk factors of AML

The exact reason why someone develops AML is not completely understood. However, researchers claim certain risk factors predispose a person to the condition, including:

  • Increasing age
  • Gender (males are susceptible to developing AML than females)
  • Exposure to toxins such as tobacco smoke
  • Exposure to certain chemicals like benzene (a solvent present in industrial emissions and petroleum refinery waste), detergents, pesticides, etc.
  • Exposure to Ionizing radiation
  • History of autoimmune disease (e.g., Psoriasis, Rheumatoid Arthritis, Autoimmune Hemolytic Anemia, Aplastic Anemia, etc.)
  • Medications of autoimmune disease (e.g., corticosteroids, anti-inflammatory agents, and immunosuppressive agents)
  • Chemotherapy for the treatment of other malignancies
  • Pre-existing disease or syndrome (e.g., Down’s Syndrome)
  • Infections (tuberculosis, pneumonia, intestinal infections, septicemia, hepatitis C, etc.)
  • Underlying genetic predisposition (e.g., family history of AML)

Signs and symptoms of Acute Myeloid Leukemia

The World Health Organization (WHO) classifies and categorizes AML and its symptoms into different groups based on the affected cell type and the causative factors. Early symptoms are generally flu-like and include:

  • Fatigue
  • Anemia
  • Anorexia
  • Fever
  • Lost appetite
  • Weight loss
  • Sweating at night

AML can involve the red blood cell line and may have the following additional symptoms:

  • Dizziness
  • Weakness
  • Pale skin
  • Irregular heartbeat
  • Cold peripheries
  • Shortness of breath
  • Headache

If you have the type of AML that affects the white blood cells, you will be vulnerable to serious infections that take a long time to treat. The following symptoms will be noted:

  • Fever
  • Weakness
  • Muscle aches
  • Diarrhea

Having AML with malfunctioning platelets leads to inappropriate blood clotting with the following symptoms:

  • Easy bruising
  • Bleeding gums
  • Bleeding that is hard to impede
  • Small red spots under your skin caused by bleeding
  • Nose bleeding
  • Sores that are difficult to heal

Invading leukemia spreads to other body parts, impairing their function too. The symptoms of AML in later stages are:

  • Balance issues
  • Blurring of vision
  • Bone or joint pain
  • Numbness in your face
  • Seizures
  • Spots or a rash on your skin
  • Swelling in your belly
  • Bleeding gums
  • Swollen glands in your groin, underarms, neck or superior to your collarbone

If you have any of the symptoms above, set an appointment with your healthcare professional as soon as possible. You might be suffering only from influenza or some other minor condition, but you should always rule out serious causes of concern. Explain your symptoms to your doctor who will take all the necessary steps to screen you for AML.

Diagnosis of AML

Your doctor may recommend specific tests to screen you for AML, as follows.

1.   Blood tests

Patients with AML have increased numbers of white blood cells (WBCs) and reduced numbers of red blood cells (RBCs) and platelets. Immature cells called blast cells (myeloblasts) that are normally present in bone marrow but not in blood are also detected.

2.   Bone marrow test

For the confirmation of diagnosis, your doctor will recommend a bone marrow test. In this biopsy a sample is taken from your marrow using a needle (commonly from the hipbone) and sent to a lab for testing.

3.   Other tests

Other tests such as the lumbar puncture (spinal tap) and genomic testing might also be required. The WHO classification of AML guides diagnosis and directs the treatment plan.

If your doctor confirms that you have AML, you may need to undergo further tests to determine its subtype and the extent of the spread of cancer in your body. The subtype of AML is established by examining the appearance of your cells under a microscope. Another special laboratory test may also be needed to identify the characteristics of your cells. Determination of your AML subtype directs the doctor for the type of treatment you will need.

Treatment plan for AML

The treatment of AML depends upon factors like your age, overall health status, the subtype of AML and your tolerance status. Although AML was previously an incurable condition, it is now cured in 35-40% of patients who are younger than 60 years of age. For the elderly, the prognosis is still evolving with time. The treatment is pursued in two phases.

1.   Induction therapy

In the first phase, the leukemic cells in the blood and bone marrow are targeted. The aim of this phase is to achieve complete remission (CR) of cancer cells. Intensive treatment is given using an anthracycline and cytarabine regimen. Daunorubicin or Idarubicin is given at a typical dose of 60-90mg/m2 and 10-12 mg/m2 respectively on days 1, 2 and 3 of the treatment along with a cytarabine infusion (100 mg/m2/daily for seven days (days 1 to 7). However, your oncologist will determine the exact dose needed for you.

Remission Induction Therapy, on the other hand, does not eliminate all the cancerous cells altogether. This makes further treatment imperative to prevent a relapse of the condition. It has been found that in 65%–73% of young patients complete remission is achieved with this standard induction therapy while 38%–62% of patients over 60 years achieve CR. Patients having a mutation in FLT3 are treated with FLT3 inhibitor midostaurin along with the standard induction therapy.

In elderly patients, hypomethylating agents including decitabine and azacitidine are found to be beneficial as initial induction therapy and for relapse. Two to four cycles of this therapy are needed on an average to achieve an optimal response.

Patients who are suspected of acute promyelocytic leukemia (APL) are to be treated with all-trans retinoic acid (ATRA) even before confirmation of the diagnosis. This will prevent the development of coagulopathy and disseminated intravascular coagulation (DIC) induced by APL. The outcomes of complete remission are even better if arsenic (ATO) is used in combination. Chemotherapy should also be started as soon as the diagnosis is confirmed.

During this phase, the levels of WBC and fibrinogen, prothrombin time and partial thromboplastin time should be monitored at least twice a day, supported by aggressive transfusion if needed. In patients having a high WBC count, steroids should be given prophylactically particularly when ATRA-ATO combination therapy is being used to prevent differentiation syndrome.

2.   Post-Induction therapy

The second phase is called post-induction therapy, consolidation therapy, maintenance therapy or intensification. It aims to get rid of the remaining cancerous cells of AML and is critical to prevent a recurrence.

In general, two main approaches to consolidation therapy exist:

  1. ChemotherapyChemotherapy is used in both the phases of AML treatment. Medicines are used to kill cancer cells. In this process, normal blood cells are also destroyed so a hospital stay is crucial for close observation and management of the patient.For patients younger than 60 years, four cycles of intermediate-dose of cytarabine is given at 1.5 g/m2 two times a day, on days 1, 3 and 5. This will effectively prolong remission and improve survival. However, transplantation is only reserved for a relapse.For patients more than 60 years, the standard dose of cytarabine used is 500–1000 mg/m2.
  2. Hematopoietic stem cell transplantation (bone marrow transplantation)A bone marrow transplant is typically done for particularly fit patients with intermediate to high-risk disease after complete remission. This remains the most effective long-term treatment for those who successfully get cured in the first round. Transplantation is considered for patients who:- Do not have any other co-morbidities
    – Have successfully achieved complete remission
    – Have a suitable donor available

The oncologist decides whether to opt for consolidation therapy or transplant, a decision largely individualized to each patient. Consolidation itself poses a risk of mortality or morbidity. A reduced-intensity allogeneic hematopoietic stem cell transplant may be considered for patients who are ineligible for a myeloablative transplant. This strategy has been found effective in older eligible patients and is becoming more common and clinically more accepted.

Relapse

Relapse occurs when major or minor remnants of leukemic cells expand that were present at the time of diagnosis or through newly developed mutations over time. Early relapse (within six months of the first complete remission), has a poor survival rate.

The prognosis is better for a second complete remission with late relapse, for those at a young age and in those with favorable genetics. A relapse therapy called salvage chemotherapy is done using Cytarabine, Fludarabine, Idarubicin as well as an MEC combination (including Mitoxantrone, Etoposide, and Cytarabine). For APL, the standard re-induction therapy includes the use of arsenic with or without ATRA.

What side effects should you expect?

Chemotherapeutic drugs work by killing rapidly dividing cells in your body. Unfortunately, these drugs also affect and destroy normal healthy cells. This affects the normal functioning of every organ in the body. The expected side effects are as follows:

  • Nausea and vomiting
  • Fatigue
  • Diarrhea and constipation
  • Hair loss
  • Mouth sores
  • Loss of appetite
  • Easy bruising
  • Increased risk for infections

Fortunately, these side effects are temporary and go away once the treatment is complete. Your doctor will treat you symptomatically to ease out side effects as possible.

Further, post-transplant immunosuppressive drugs help you avoid rejection and further complications. A suppressed immune system makes you vulnerable to other sprouting illnesses like infections, poor wound healing, and so on. Be watchful of your environment.

Coping with AML

Coping with cancer is extremely difficult in itself. On top of that, facing the world is another dilemma you need to face. Try to accept your condition and talk to your family and friends about your diagnosis. Let out your fear and gather yourself back. Stay composed and work things out so that everything falls in place in the best possible way for you.

Keep yourself protected from pollution and from people who can be potential sources of transmitted infections like flu, cough, tuberculosis (TB), and so forth. Viral infections would further complicate your already debilitating health. Some ways to avoid these complications are to use a face mask while going out, wear gloves before touching any potentially contaminated surface, wash your hands often, and eat whole organic foods.

Lastly, have faith in yourself and never stop fighting. Remember that after a deep dark night, there can be sunshine.

 

 

 

References

Cancer.net Editorial Board, (01/2019) Leukemia – Acute Myeloid – AML: Statistics. Obtained from: https://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml/statistics

Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Development and Causes of Cancer. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9963/

De Kouchkovsky, I., & Abdul-Hay, M. (2016). ‘Acute myeloid leukemia: a comprehensive review and 2016 update’. Blood cancer journal, 6(7), e441. doi:10.1038/bcj.2016.50

Döhner, H., Estey, E., Grimwade, D., Amadori, S., Appelbaum, F. R., Büchner, T., … Bloomfield, C. D. (2017). Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood, 129(4), 424–447. doi:10.1182/blood-2016-08-733196

Döhner, H., Estey, E., Grimwade, D., Amadori, S., Appelbaum, F. R., Büchner, T., … Bloomfield, C. D. (2017). Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood, 129(4), 424–447. doi:10.1182/blood-2016-08-733196

Estey E, Döhner H. Acute myeloid leukaemia.Lancet. 2006 Nov 25;368(9550):1894-907. DOI: 10.1016/S0140-6736(06)69780-8

Kawamoto H, Minato N. Myeloid cells. Int J Biochem Cell Biol. 2004 Aug;36(8):1374-9. DOI: 10.1016/j.biocel.2004.01.020

Kristinsson, S. Y., Björkholm, M., Hultcrantz, M., Derolf, Å. R., Landgren, O., & Goldin, L. R. (2011). Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 29(21), 2897–2903. doi:10.1200/JCO.2011.34.8540

Rachel Nall, Christina Chun. Survival Rates and Outlook for Acute Myeloid Leukemia (AML). Obtained from: https://www.healthline.com/health/acute-myeloid-leukemia-survival-rates-outlook

Saultz, J. N., & Garzon, R. (2016). Acute Myeloid Leukemia: A Concise Review. Journal of clinical medicine, 5(3), 33. doi:10.3390/jcm5030033

 

AML Research and Internet Claims Program Resource Guide

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