Diagnosis and Treatment of ALL
Acute Lymphoblastic Leukemia: Diagnosis and Treatment
Acute lymphocytic leukemia (ALL), also known as acute lymphoblastic leukemia, is a type of bone marrow and blood cancer that progresses rapidly. The word “acute” signifies that it progresses and spreads very quickly, and “lymphocytic” refers to lymphocytes, which are a type of white blood cells.
It first starts in the bone marrow and affects blood cells and other parts of the body very quickly. And since ALL is a rapidly progressing disease, prompt diagnosis and the appropriate treatment are extremely important.
So here is everything you need to know about the diagnosis and treatment for acute lymphocytic leukemia.
Diagnosing any type of cancer, including ALL, requires a series of multiple tests. These tests will allow the medical professional to reach the exact diagnosis which will, in turn, help them to decide which treatment would be the best for the patient.
So, in order to reach an ALL diagnosis, the doctor will have to perform the following tests.
Doing a blood test is usually the first step in diagnosing any disease because it helps medical professionals determine many different things. For example, it can show the amount of white and red blood cells as well as platelets a patient has.
There are two different types of blood tests a doctor will order if they suspect a patient is suffering from ALL: complete blood count (CBC) with differential and a peripheral blood smear.
Complete Blood Count (CBC) with Differential
A complete blood count (CBC) with a differential is used to measure the number of red and white blood cells as well as platelets in the patient’s body. It includes a differential that measures all the blood cells.
If a patient has ALL, the number of their white blood cells is higher than normal but they have fewer platelets and red blood cells.
Peripheral Blood Smear
A peripheral blood smear is also used to examine the patient’s red and white blood cells and platelets. However, what makes this blood test different from others is that it doesn’t use a machine to analyze the blood.
Instead, a team of healthcare providers observes the blood under a microscope and looks for any abnormalities.
To perform a PBS, the medical professionals will spread a drop of the patient’s blood on a glass plate, turn it into a thin film, and then treat it with chemicals. These chemicals highlight the specific characteristics of the blood and make them easier to see.
Bone Marrow Aspiration and Biopsy
Even though a blood test can determine a potential issue the patient may have, it can’t help a doctor make a complete diagnosis. And so the next stage of diagnosing acute lymphoblastic leukemia is bone marrow aspiration and biopsy.
Since ALL first starts in the bone marrow, this test is crucial in the diagnosis stage.
For a bone marrow aspiration and biopsy, a medical professional will remove part of the bone marrow, a piece of bone, and some blood from the patient’s body. This is done by inserting a needle into either the breastbone or the hipbone.
Afterward, a pathologist will examine the bone, bone marrow and blood under a microscope. While doing this, they will look for anything that could be a sign or indication of cancer.
If a doctor wants to diagnose acute lymphocytic leukemia and/or determine what specific subtype of ALL a patient has, they will order one or more of the following lab tests.
A cytochemistry lab test is done exactly what type of leukemia a patient suffers from.
To perform this test, a medical professional will put the patient’s cells on a slide and expose them to certain dyes known as chemical stains. And when in contact with these stains, cells have a reaction and change their color.
What’s interesting about cytochemistry is that it stains certain types of cells while leaving the others untouched, which can be of great help to the pathologist looking at them.
For example, there is one particular stain that won’t have any effect on most ALL cells, but it will turn parts of acute myeloid leukemia (AML) cells black.
Flow Cytometry and Immunohistochemistry
Flow cytometry and immunohistochemistry are very similar types of lab tests, and their purpose is the same. For these two types of tests, medical professionals use antibodies to treat cell samples.
These antibodies are proteins that only stick to certain cells or other proteins. With these two techniques, doctors can detect antigens that are located either on the surface or inside of cells, and this helps determine whether a disease is present.
However, there are a few differences between these two tests. The biggest difference is that flow cytometry is a laser-based technique and immunohistochemistry microscopy-based technique. Additionally, flow cytometry uses a laser beam and immunohistochemistry uses antibodies.
Both of these tests have their advantages and they can both be used to detect and diagnose ALL, and the doctor who is in charge of treating the patient will determine which one of these two tests would be better suited for their individual needs.
Chromosomes are long strands of DNA that are found inside cells. When a person is healthy and doesn’t have any issues, their cells contain a total of 23 pairs of chromosomes. However, that’s not the case for those suffering from acute lymphocytic leukemia.
In some cases, ALL causes chromosomal changes within the cells, and while there can be multiple different changes that occur, the most common one is translocation.
Translocation causes chromosome 22, also known as the Philadelphia chromosome, to become shorter. This is a common occurrence with acute lymphoblastic leukemia and it affects approximately 25% of adults with ALL.
Since ALL may cause chromosomal changes and disorders, a chromosome test is used as part of the diagnostic process.
For a cytogenetics chromosome test, cells are grown in a lab dish inside a sterile environment until they start dividing. Once they do, a medical professional examines the chromosomes under a microscope to see whether there are any abnormalities or changes.
Fluorescent in Situ Hybridization (FISH)
The second way to perform a chromosome test is via a fluorescent in situ hybridization, or FISH for short, is a type of test that’s performed using special fluorescent dyes. These dyes only attract certain chromosomes or genes.
This test can detect most chromosomal changes that occur due to ALL which are visible under a microscope just like during a cytogenetics test, but it can also detect the changes that are too small to be caught with cytogenetic testing.
Lumbar Puncture (Spinal Tap)
ALL spreads very quickly, and it can easily reach the area around the brain and spinal cord. Doctors check whether the tumor has reached this area by testing a sample.
To perform a spinal tap, a doctor will place a small and hollow needle between two spinal bones and insert it into the area surrounding the spinal bone. They will then collect fluid to be tested.
In some cases, the doctor will also inject some chemotherapy drugs during the patient’s lumbar puncture to start treating leukemia that has already spread or even prevent it.
Imaging tests aren’t as useful for diagnosing leukemia as they are for diagnosing other kinds of cancer, and that is because leukemia usually doesn’t create tumors. However, imaging tests can be used to determine if it’s spread to other parts of the body, the extent of the disease, and if a different issue occurred.
If a doctor suspects the patient’s leukemia led to a lung infection, they will order a chest X-ray. This imaging test is also used to check for the presence of enlarged lymph nodes in the patient’s chest.
Computed Tomography (CT) Scan
A CT scan creates cross-sectional images of the patient’s body with the use of X-rays and it shows whether any organs or lymph nodes in the patient’s body are enlarged. A CT scan isn’t done to diagnose leukemia but it can show whether leukemia cells are growing inside an organ.
Magnetic Resonance Imaging (MRI)
MRI scans create detailed images of the patient’s body with the help of strong magnets and radio waves, and they are often used when a medical professional wants to examine the spinal cord or brain.
Positron Emission Tomography (PET) Scan
Positron emission tomography scans are seldom used by themselves for ALL, but they can sometimes be used in conjunction with CT scans.
PET scans allow doctors to determine whether there is increased cell activity in a specific area and the CT scan will provide more detail in that area. This allows doctors to pinpoint tumors more easily, but it also exposes the patient to more radiation than necessary.
An ultrasound is an imaging test that can be used to observe lymph nodes that are located near the body’s surface. It can also allow the doctor to look for any enlarged abdominal organs; these include the liver, kidneys and spleen.
Getting Diagnostic Results
After the doctor performs all the necessary tests and determines that their patient is suffering from ALL, they will give them the diagnosis.
Getting diagnostic results is not easy for any disease, especially cancer. However, if you get an ALL diagnosis, your doctor will guide you through what that diagnosis entails, what you can expect and what your treatment will look like.
When the time comes to receive treatment for ALL, the doctor will discuss all the different treatment options with the patient as well as what they can expect.
Factors That Affect Prognosis and Treatment
A patient’s prognosis is the description of the overall forecast or outlook of their leukemia. Some of the things that factor into the prognosis include the patient’s symptoms, treatment requirements and recovery.
There are also a variety of factors that will affect what kind of treatment the patient will receive and how aggressive it will have to be.
These factors include:
- Age: ALL is a disease that mostly affects children between the ages of 1 and 9, but it can still occur in patients of all ages. And the age of the patient when they’re diagnosed will influence their chances of survival and the type of treatment that should be used.
- The state of chromosomes: As we already mentioned, a healthy human body has 46 chromosomes, but those suffering from ALL can have more or fewer. The patient’s outlook will greatly depend on the number of chromosomes they have as well as the condition they’re in.
- The ALL subtype: There are a couple of different subtypes of acute lymphoblastic leukemia, and all of them require different treatments.
- White blood cell count: The patient’s blood cell count can in some cases determine how aggressive their treatment needs to be. For example, those who have a high number of white blood cells will require a more aggressive form of treatment.
Staging refers to how far the disease has progressed, and these are the stages of acute lymphoblastic leukemia:
- Untreated ALL: Untreated ALL means that the leukemia was just diagnosed and the patient hasn’t gone through treatment yet. Untreated adult ALL and untreated childhood ALL are both defined by a low number of blood cells and platelets and more than 5% leukemia cells in the patient’s bone marrow.
- ALL in remission: When leukemia is in remission, the ALL has been treated and the complete blood count has returned to normal, and there are less than 5% leukemia cells in the bone marrow. This is true for both untreated adult ALL and untreated childhood ALL.
- Recurrent ALL: After the disease has been treated and the patient has gone through remission, the disease could come back. This is defined as recurrent adult ALL, or recurrent childhood ALL, depending on the age of the patient.
ALL Treatment Phases
When a patient gets diagnosed with acute lymphoblastic leukemia, they will receive their treatment in four different phases.
Treatment for ALL starts soon after the patient receives their diagnosis, typically within a couple of days, and the first phase of treatment is induction chemotherapy. This process usually lasts for approximately 4 weeks.
As the name suggests, during this phase of treatment, the patient will receive rounds of chemotherapy accompanied by intensive supportive care. The goal of induction chemotherapy is to return the patient’s blood counts to normal and significantly lower the number of leukemia cells in the bone marrow.
ALL can easily spread to the spinal fluid, and if that happens, the patient will have to receive chemotherapy directly into the fluid.
This is known as CNS treatment, and it involves the doctor inserting a needle between the vertebrae that are located in the lower back and infusing the chemotherapy drugs. During this treatment, the patient will receive six or more injections.
Consolidation Therapy (Intensification)
For more aggressive forms of ALL, the patient will most likely have to receive consolidation therapy, also known as intensification.
Consolidation therapy involves giving the patient multiple rounds of intensive chemotherapy for about 6-9 months. During this time, the patient will require frequent hospitalization and intensive supportive care.
After going through intensive chemotherapy, the patient will have to take oral chemotherapy pills as part of their maintenance therapy. This can last for anywhere from 18 to 24 months and during this time the patient will get blood tests once a month.
ALL Treatment Options
Treatment options refer to the type of treatment the patient receives. Even though chemotherapy is the most common treatment option for this and other types of cancer, it’s not the only one.
Chemotherapy is the most common treatment option for acute lymphoblastic leukemia and it involves the use of special drugs to target and destroy cancer cells. The therapy is administered by either an oncologist or a hematologist.
Chemotherapy can be given intravenously or orally in pill/capsule form, and the patient will have to go through multiple rounds of chemotherapy throughout their treatment.
Radiation therapy, also known as radiotherapy, is the process of destroying cancerous cells with the use of high-energy X-rays. It is performed by a radiation oncologist and is administered for a set period of time and in multiple rounds, just like chemotherapy.
Radiotherapy is often used instead of chemotherapy when the cancer is still in its early stages and only affects some smaller areas.
Targeted therapy is a treatment option that stops cancer cells from growing and spreading, and it does so by targeting the specific proteins, genes or tissue environment of the cancer.
For ALL, targeted therapy is often used in combination with chemotherapy because these two combined treatment options have the biggest chance of a successful outcome.
Bone Marrow Transplant
Since acute lymphoblastic leukemia appears in the bone marrow, this treatment option is often necessary.
A bone marrow transplant is a special medical procedure during which the infected bone marrow that has leukemia cells in it is destroyed and then replaced with healthy and specialized stem cells. Over time, these cells make their way into the bloodstream and afterward into the bone marrow.
After a patient has gone through all stages of ALL and has been successfully treated for the disease, the next step is follow-up care.
If you choose to seek treatment at Sheba Medical Center, not only will you receive the best possible treatment, but we will also ensure your follow-up care is as smooth and pleasant as possible.
During follow-up care, you will receive regular medical checkups, be given the chance to talk about your physical and emotional issues and simply receive the support you need during this time.
Dr. Ofer Margalit completed M.D. degree, as part of an M.D.-
Specializing in breast cancer treatment, Dr. Tal Shapira-Rot
Dr. Meital Levartovsky is a senior oncologist in GU Unit at
Dr. Moran Gadot is a senior oncologist in GU unit at the Can
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