Diagnosing CML

Sometimes, people with CML are diagnosed (without presenting any symptoms) because their doctor decided to order more tests after noticing something unusual on a blood test performed for another reason or as part of a routine health screening.

"Way back when I was chief resident and later on, as the assistant chairman of medicine at Memorial Sloan Kettering in NYC, when we saw a patient with CML, they were usually very ill," Dr. Arena recalls. "We didn't pick up the disease as quickly as we now do. These days, every person who comes in for a routine physical or for some type of checkup gets a blood count."

"I can't tell you how many times a week someone is referred to me because their white blood cell count is elevated."

When a blood test is suspicious, further screening is advised, which may include a Complete Blood Count (CBC), bone marrow samples, and/or genetic testing.

Complete Blood Count (CBC)

Before symptoms develop, as Dr. Arena said, most people who have CML find out by having a routine blood test called a CBC or complete blood count. A CBC sees how many different kinds of cells are in your blood: red blood cells, white blood cells, and platelets (which are pieces of very large cells in the bone marrow called megakaryocytes). People with CML often have low numbers of red blood cells or blood platelets. If your blood test results show a high number of white blood cells it's an indication that you might have CML.

From there, other screening tests will be recommended by your healthcare provider. This may include bone marrow samples or genetic tests.

Bone Marrow Samples

Since leukemia begins in the bone marrow, checking to see if the patient has CML with a marrow sample is a crucial step. People with CML often have bone marrow that is hypercellular meaning it has more blood-forming cells than a normal sample would contain. These two tests are usually done at the same time:

1. Bone marrow aspiration For this procedure, a doctor or nurse makes a small incision in your skin while you're lying on your side or on your stomach. A hollow needle is inserted into the bone and into the bone marrow, usually collected from the top ridge of the hipbone. Using a syringe attached to the needle, a sample of the liquid portion of the bone marrow is withdrawn.
2. Bone marrow biopsy This procedure is most often done immediately following the bone marrow aspiration. A slightly bigger needle is pushed down into the bone and a small piece of both bone and marrow is removed.

Dr. Tiffany Tanaka, a hematologist/medical oncologist at UC San Diego, explains the purpose of a bone marrow biopsy.

Genetic Tests

Gene testing to look for the BCR-ABL gene or for the Philadelphia chromosome is recommended. Genetic testing for both the BCR-ABL gene and the Philadelphia chromosome is done by analyzing blood samples.

1. Testing for the Philadelphia chromosome Normal cells have 23 pairs of chromosomes and each is a certain size, but it is common for the cells in CML patients to have an abnormal chromosome called the Philadelphia (Ph) chromosome. Screening for the Ph chromosome helps the doctor to diagnose CML.
2. Conventional Cytogenetics It's often recommended to have sample of chromosome (pieces of DNA) examined under a microscope to look for any changes. Since chromosomes can be seen most clearly when they are in the process of dividing, a sample of either your bone marrow or blood is grown in a laboratory to get the cells to begin to divide. The drawback to this test is that it takes time (usually around 30 days) and doesn't always work.
3. Fluorescent in situ hybridization (FISH) Using fluorescent dyes that only attach to specific genes or parts of chromosomes, this test looks for specific pieces of the BCR-ABL gene. It can be done using regular blood or bone marrow samples without needing to grow the cells in a lab.
4. Polymerase chain reaction (PCR) This test is designed to not only find the BCR-ABLE gene in CML cells but it also measures how much is there. Using blood or bone marrow samples, the test is so sensitive that is able to detect small amounts of BCR-ABL, even when cytogenetic testing doesn't find the Philadelphia chromosome in bone marrow cells.

Treatment for Chronic Myeloid Leukemia

The main treatment for CML is targeted cancer drugs (known as tyrosine kinase inhibitors). Other possible treatments include chemotherapy and a stem cell transplant.

Different treatment approaches will be used in different situations:

• Targeted Treatment: For most people, CML is treated with an oral medication, called a tyrosine kinase inhibitor (TKI). This medication blocks the effects of BCR:ABL1 (the abnormal protein found in people with CML).
• Chemotherapy: These drugs carry toxic substances that inhibit the cancer cells. These are mostly used when TKIs aren't effective, or they cause intolerable side effects. (ex. Omacetaxine – brand name: Synribo).
• Stem cell transplantation: Also called bone marrow transplantation, this is usually used after the disease stops responding or relapses during treatment with a TKI.
• Symptom control: Certain chemotherapy medications (hydroxyurea, busulfan, or interferon alfa) may be used to reduce symptoms of CML in special circumstances, although they do not cure the disease.

Dr. Javier Pinilla, a hematologist/oncologist at Moffitt Cancer Center, explains how TKIs are used to treat CML.

How Do TKIs Work?

Targeted cancer drugs can change the way that cells work and help the body control the growth of cancer. The main type for CML are tyrosine kinase inhibitors. TKIs are an oral medication and they are the initial treatment of choice for most people with CML.

The Philadelphia chromosome, which is a defining characteristic of CML, produces an abnormal protein called BCR-ABL1. TKI treatment blocks the effects of BCR-ABL1, which rapidly kills CML cells.

More than two-thirds of patients with chronic phase CML achieve long-term control of the disease with TKIs. Although TKIs have not been proven to cure CML, people who have an excellent response to TKI therapy have expectations for survival that are similar to age-matched individuals without CML. The rates of progression have reduced significantly from over 20% in the pre-TKI era to less than 5% now.

There are several different kids of TKIs used for CML, including:

• Imatinib mesylate (brand name: Gleevec)
• Dasatinib (brand name: Sprycel)
• Nilotinib (brand name: Tasigna)
• Bosutinib (brand name: Bosulif)
• Ponatinib (brand name: Iclusig)
• Asciminib (brand name: Scemblix)

Sometimes the CML cells are tested to see if they have genetic changes (mutations) that may mean that a certain TKI is more or less likely to work. Two newer TKIs, Scemblix® (asciminib) and Iclusig® (Ponatinib), are sometimes used for patients who have not responded to other TKI treatment.

TKI Side Effects

The decision of which TKI to use is usually based on potential side effects, your medical history, and cost. Most people can return to their usual daily activities after starting treatment with a TKI. The side effects of tyrosine kinase inhibitors are usually mild and should improve with time. They can include:

• Fatigue (feeling and being sick/tiredness)
• Headaches
• Abdominal (tummy) pain
• Swelling in the face and lower legs
• Muscle cramps/pain
• Rash
• Diarrhea

Regular blood tests and occasional tests of your bone marrow will be carried out to check whether the treatment is working. If it does work, it will usually be taken for life.

The primary goals of treatment are to relieve symptoms, help you live as long as possible, and prevent your CML from progressing to the blast phase. Achieving these goals generally requires markedly reducing the number of cells that contain the abnormal “Philadelphia chromosome” and enabling the return of normal (non-leukemic) blood cells.

Living With CML

If you have recently started TKI treatment, you will need to be regularly monitored to ensure you are tolerating the drugs and they are working in the way they are supposed to.

"When someone starts a TKI, what's nice is you can take this pill at home, but it does require a good deal of work for the patient to do. It really does require a diligent patient and a diligent physician to follow up on the labs," Dr. Tiffany Tanaka, hematologist/medical oncologist at UC San Diego, tells SurvivorNet. Initially this could mean undergoing tests every week.

Dr. Tiffany Tanaka, hematologist/medical oncologist at UC San Diego, explains how CML patients are monitored after beginning TKI treatment. 

Response to these drugs can be measured in many ways, including using hematologic (complete blood count, or CBC), cytogenetics, or molecular analyses.

• CBC distinguishes between partial and complete hematologic responses to treatment (how close blood counts have returned to normal).
• When gauging treatment response cytogenetically, the percentage of the marrow and blood cells with Ph chromosomes dictates the patient response level.
• A molecular response is measured using a very sensitive test called the quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) test to measure the levels of the BCR-ABL1 fusion gene within the blood or bone marrow.

A combination of CBC, cytogenetics and Q-RT-PCR is recommended at regular time intervals to monitor treatment response. During the first year, treatment response is evaluated every 3 months. After the first year, testing can be spaced out more for patients with a good response.

Navigating the Cost of Treatment

While there has been major progress in treating CML (with TKIs), the cost of treatment still remains an issue. Other than the medication itself, the cost also includes necessary follow-up, regular blood work, management of side effects from the treatments, and future need for chemotherapy or bone marrow transplants.

Most health insurance companies will cover CML medication and treatment costs, but your policy may not always cover everything. For example, some insurance companies will cover only one type of TKI. However, there are other options patients can consider if they are having issues with their insurance (or they do not have insurance).

"Can you imagine covering 80% of a drug that causes a hundred thousand per year? So that's the reason that companies and, Leukemia & Lymphoma Society, and other societies such as CML Society try to help patients to overcome these financial problems," Dr. Javier Pinilla, head of the Lymphoma Section at Moffitt Cancer Center, explains.

Dr. Javier Pinilla, a hematologist/oncologist at Moffitt Cancer Center, discusses how CML patients can get help paying for cancer treatment. 

There are several options patients struggling to pay for treatment can consider, including:

• Asking for a financial counselor, social worker, and/or nurse navigator (at your cancer center) who can create a plan that works for you.
• Looking into your coverage to determine how much copays and other out-of-pocket costs may be beforehand.
• Discussing generic drug options with your doctor.
• Discussing the need to get prior authorization request with your doctor to determine whether the drug is covered.
• If your claim is denied, your doctor may also need to file an appeal with the insurance company. This can happen if you are prescribed a newer generation of TKI.
• You may be eligible for Medicare Part D or Medicaid even if you have health insurance.