Acute Monocytic Leukemia: Clinical features, Diagnosis, and Treatment

Introduction

Acute monocytic leukemia (AML-M5), a subtype of acute myeloid leukemia (AML), is a rare but aggressive blood cancer that requires prompt diagnosis and intervention. AML-M5 primarily affects the myeloid cells in the bone marrow and blood. The rapid proliferation of immature monocytic cells characterizes it. While the exact cause of AML-M5 remains unknown, several risk factors exist, such as exposure to certain chemicals, radiation, and genetic predisposition.

What Are the Clinical Features of Acute Monocytic Leukemia?

The following are the features of acute monocytic leukemia:

• Rapid Proliferation of Immature Monocytic Cells: AML-M5 is characterized by the uncontrolled growth of immature monocytic cells in the bone marrow and blood. These cells fail to mature into healthy white blood cells essential for the body's immune system.

• Fatigue and Weakness: One of the hallmark symptoms of AML-M5 is persistent fatigue and weakness. This occurs because the leukemia cells overcrowd the bone marrow, reducing the production of normal red blood cells and leading to anemia. Anemia results in reduced oxygen delivery to tissues, causing tiredness and weakness.

• Frequent Infections: The proliferation of abnormal monocytic cells can suppress the production of functional white blood cells. This weakened immune system leaves patients vulnerable to frequent infections, which can be severe and difficult to treat.

• Bleeding and Bruising: AML-M5 can lead to low platelet counts, a condition known as thrombocytopenia. Platelets are essential for blood clotting, so that low platelet levels can result in easy bruising and excessive bleeding, even from minor injuries or cuts.

• Bone Pain: The presence of leukemia cells gathering in the bone marrow can result in bone pain and uneasiness. This discomfort is typically characterized as a profound, throbbing sensation and can manifest in different areas of the body, such as the ribs, sternum, and extended bones.

• Enlarged Liver or Spleen: In some cases, patients with AML-M5 may develop an enlarged liver (hepatomegaly) or spleen (splenomegaly). The presence of leukemia cells in these organs can cause them to increase in size, leading to discomfort and other symptoms such as abdominal pain and fullness.

• Other Symptoms: Beyond the common clinical features mentioned above, individuals with AML-M5 may experience additional symptoms, including fever, weight loss, and night sweats. These symptoms are generally associated with the body's response to the leukemia cells and the impact of the disease on various organs and systems.

How Is the Diagnosis of Acute Monocytic Leukemia Done?

Diagnosing AML-M5 involves a comprehensive evaluation of the patient's medical history, physical examination, and several specific tests and examinations to confirm the presence of acute monocytic leukemia.

Blood Tests (Complete Blood Count - CBC):

• A CBC is often one of the initial tests conducted when leukemia is suspected.

• It measures the levels of different blood components.

• In AML-M5, the CBC typically reveals abnormal results. This could involve a notable rise in undeveloped white blood cells, a reduction in normal white blood cells, and a decrease in both red blood cells and platelets. These findings can raise suspicion of leukemia.

Bone Marrow Biopsy and Aspiration:

• This is a crucial diagnostic procedure that provides definitive evidence of leukemia.

• A small sample of bone marrow tissue is extracted during a bone marrow biopsy, usually from the hip bone (pelvic bone).

• The bone marrow sample that has been collected is subsequently scrutinized using a microscope to determine if leukemia cells are present, type (monocytic in this case), and quantity.

• Additionally, the biopsy can help evaluate the degree of involvement of the bone marrow by leukemia cells.

Cytogenetic Testing:

• Cytogenetic testing involves studying the genetic material (chromosomes) within leukemia cells.

• This test can identify specific genetic mutations or chromosomal abnormalities critical for treatment planning.

• Some genetic mutations may have prognostic significance, influencing the choice of therapy and predicting the likelihood of treatment success.

• Examples of relevant genetic mutations in AML-M5 include the presence of certain translocations or mutations in genes like FLT3, NPM1, and CEBPA.

Immunophenotyping (Flow Cytometry):

• Immunophenotyping is a laboratory technique that uses flow cytometry to analyze specific surface markers or antigens present on the surface of leukemia cells.

• By examining these markers, hematologists can classify the subtype of leukemia more precisely, distinguishing AML-M5 from other AML subtypes.

• This information helps tailor treatment strategies, as different subtypes may respond differently to therapies.

How Is Acute Monocytic Leukemia Managed?

Treatment for acute monocytic leukemia (AML-M5) is complex and tailored to the individual patient's specific circumstances, including their age, overall health, and the genetic profile of the leukemia cells.

Chemotherapy:

Chemotherapy is the primary treatment for AML-M5 and is typically administered in multiple phases:

• Induction Therapy: In the first stage of treatment, the primary objective is to attain remission, which involves decreasing the quantity of leukemia cells in the bone marrow and peripheral blood to a point where they cannot be detected under a microscope. This typically involves intensive chemotherapy with a combination of drugs. The goal is to destroy as many leukemia cells as possible and allow normal bone marrow function to recover.

• Consolidation Therapy: After achieving remission, consolidation therapy is given to reduce the risk of relapse further. It involves additional rounds of chemotherapy to eliminate any remaining leukemia cells that may not be detectable but could lead to deterioration.

The specific chemotherapy regimen may vary, but common drugs used in AML-M5 treatment include Cytarabine and anthracyclines (e.g., Daunorubicin or Idarubicin).

Targeted Therapy:

Targeted therapy medications are created to pinpoint particular molecules or pathways that play a role in the development and persistence of leukemia cells. The selection of a targeted therapy is determined by the genetic characteristics of the leukemia cells. For example:

• FLT3 Inhibitors: If the leukemia cells have mutations in the FLT3 gene, drugs like Midostaurin or Gilteritinib may target these mutations.

• IDH Inhibitors: In cases with IDH1 or IDH2 mutations, targeted drugs like Ivosidenib or Enasidenib can be employed.

Stem Cell Transplant (Hematopoietic Stem Cell Transplant - HSCT):

• Stem cell transplant may be considered, particularly for patients with high-risk AML-M5 or those who achieve remission after induction therapy but have a high risk of relapse.

• HSCT (hematopoietic stem cell transplantation) entails substituting the patient's unhealthy bone marrow with viable stem cells sourced from either a compatible donor (allogeneic transplant) or the patient's own body (autologous transplant).

• Allogeneic HSCT offers the advantage of the graft-versus-leukemia effect, where the transplanted immune cells attack and eliminate any remaining leukemia cells.

• Autologous HSCT is less commonly used in AML-M5 and involves collecting the patient's stem cells before high-dose chemotherapy and then reinfusing them after treatment.

Supportive Care:

Supportive care is integral to AML-M5 treatment to manage side effects and complications associated with chemotherapy and the disease itself.

This may include:

• Blood Transfusions: To address anemia and low platelet counts.

• Antibiotics: To prevent and treat infections, a common concern due to a weakened immune system.

• Growth Factors: To stimulate the production of blood cells by the bone marrow.

• Pain Management: To address bone pain and other discomforts.

• Nutritional Support: Ensuring adequate nutrition to maintain strength and energy.

Conclusion

The prognosis for AML-M5 varies based on several factors, including the patient's age, overall health, genetic profile of the leukemia cells, and response to treatment. Remission is a significant milestone, but long-term outcomes depend on preventing relapse.