Atypical chronic myeloid leukemia (aCML) is a blood and bone marrow cancer. A person with aCML has a disorder in the bone marrow cells responsible for producing blood cells, but doctors do not know why this happens.
Myelodysplastic/myeloproliferative (MDS/MPN) neoplasms are a group of blood and bone marrow diseases. ACML is one of the conditions in this group.
In people with aCML, their bone marrow cells reproduce excessively, resulting in many abnormal, immature white blood cells, known as blasts.
Any type of white blood cell can reproduce in aCML. However, it is typically a specific granulocyte called neutrophils that uncontrollably multiplies in people with aCML.
Neutrophils are the most common white blood cells, accounting for 40–60% of all white blood cells. Neutrophils are responsible for protecting the body from infection and inflammation.
In this article, we examine aCML and its symptoms. We also discuss how aCML differs from CML and the potential treatments.
The condition known as aCML involves the bone marrow and the peripheral blood. The considerable number of abnormal, immature bone marrow cells that occur with aCML prevents the bone marrow from producing enough healthy blood cells.
It causes anemia and thrombocytopenia, and related symptoms, due to the reduced number of healthy blood cells. People may also experience spleen enlargement.
Symptoms of aCML include:
- difficulty breathing
- pale appearance
- bruising and bleeding
- pinpoint spots under the skin
- pain below the ribs on the left side
Unexplained weight loss, night sweats, and poor appetite can also be symptoms of aCML.
Both aCML and CML share similar clinical features, but they have some differences, such as:
Under a microscope, the leukemia cells in aCML and CML look alike. However, a particular chromosome change in CML, known as the Philadelphia chromosome, is absent in aCML.
Each cell contains 23 pairs of chromosomes made of DNA with the instructions for every cell in the body. The Philadelphia chromosome is a specific gene abnormality where chromosome 9 and chromosome 22 break and exchange portions. This results in an abnormally small chromosome 22 and a new set of cell instructions that lead a person to develop CML.
Hypercellular bone marrow
Normally, the ratio of myeloid cells to erythroid precursor cells (M:E) in the bone marrow is around 1.2:1 to 5:1. In people with CML, this rises to an M:E ratio of 10:1 to 30:1. This increased production of cell lineages means that the bone marrow has an abnormal excess of cells, known as being hypercellular.
Although the bone marrow is also hypercellular in aCML, the M:E ratio is usually less than 10:1.
Basophilia occurs less often in aCML compared with CML. A basophil is a type of white blood cell, and basophilia means too many basophils in someone’s blood.
The average age of diagnosis with CML is around 64 years, while the age of diagnosis for aCML tends to be about 73 years.
ACML is a more aggressive disease, which can progress within 2 years, compared to CML, which develops gradually and progresses slowly. People with aCML may develop acute leukemia or bone marrow failure.
Doctors diagnose aCML by taking blood and bone marrow samples. They may use diagnostic tests, such as:
- a complete blood count (CBC) with a differential WBC count
- bone marrow aspiration and biopsy
- chromosome analysis
- imaging tests, such as a CT scan, MRI, or ultrasound
There is no existing standard of care or established guidelines currently to manage aCML. However, some research suggests hematopoietic stem cell transplantation (HSCT) may
A 2020 review states that doctors may use several treatment strategies for aCML, including:
- Erythropoiesis stimulating agents (ESAs): ESAs stimulate red blood cell (RBC) production to counter anemia.
- Hypomethylating agents (HMAs): HMAs are a bridging therapy for people having HSCT and stand-alone treatment for those who are not eligible for transplants.
- Acute myeloid anemia (AML) induction therapy: This therapy induces remissions to treat acute leukemia.
- Hydroxyurea (HU): Treats cancer by stopping cancer cell growth.
- Pegylated interferon alfa: This contains interferon, naturally occurring proteins in the body that inhibit viruses from multiplying and growing, and polyethylene glycol, which enhances the effect of interferon in the body.
- Targeted therapies: These therapies use targeted agents like JAK inhibitors and tyrosine kinase inhibitors to attack specific abnormalities in cancer cells without harming healthy cells. Doctors only give these to individuals if they detect the relevant gene mutations from mutation analysis.
A 2019 case report mentions that AML-like chemotherapy with HSCT is the only treatment option to cure aCML.
People with aCML often need lifelong treatment and require continuous follow-up with several doctors within a treatment team. Treatment for aCML is expensive, even if an individual has insurance.
Individuals also need to cope with the side effects that come with medications.
As with other types of cancer, people with aCML have an increased risk of having depression and anxiety.
Since aCML is a rare condition, there are currently limited studies on treatment strategies for the disease.
The outlook for people with aCML depends on the number of red blood cells and platelets in their blood.
The average survival for people with aCML is 10.8 to 25 months. Several studies suggest that aCML may develop into AML.
ACML is a rare leukemic disorder with an unknown cause. There is currently no existing standard of care, and treatment results vary. As researchers conduct more studies on the condition and its potential treatments, the outlook for people with aCML may improve.
Individuals need to discuss their options with healthcare professionals in their care team to reach a treatment plan that best meets their needs.