Leukemia in the Elderly: A Clinical Aspect

Introduction:

In normal conditions, every function of the body cells is regulated by several factors. Not only this but the normal cellular characteristics are also maintained. However, in certain situations, the normal form and the functions of the cells are lost. This is associated with abnormal cell divisions. This condition is known as cancer. Cancer is one of the most dangerous illnesses of modern times. It is known for major changes in the quality of life, health status, and deaths.

What Is Leukemia in the Elderly?

In the United States of America, each year, almost 43000 elderly individuals are affected by leukemia. The most common leukemia seen in elderly patients is acute myeloid leukemia. The causative factors associated with this are;

1. Genetics plays a vital role in the onset of acute myeloid leukemia in elderly people. The most commonly affected genes in elderly acute myeloid leukemia are TET2, DNMT3A, NPM1, SRSF2, and ASXL1. Other than this, mutations of TP53 and IDH are also seen in such cases.

2. Another causative factor that is associated with the onset of acute myeloid leukemia in the elderly is the presence of disorder-like antecedent myelodysplastic syndrome (MDS, a group of bone marrow disorders). Around 22 of 100000 people over the age of 70 suffer from this condition. Such conditions are mainly caused by the abnormality of the bone marrow. Aging is the primary cause of pathological changes in the bone marrow. Apart from this, factors like systemic disorders, malnutrition, smoking, alcoholism, and exposure to environmental carcinogens are associated with such complications. This condition is responsible for abnormal functioning of the bone marrow, pathological changes in the marrow cells, and decreased functioning of the bone marrow.

3. Retrovirus infection, such as the human T-cell leukemia virus, is also associated with chronic lymphocytic leukemia in the elderly. However, the incidence of this complication is extremely rare. Such cases are only seen in southern Japan and the Caribbean.

Needless to say, the characterization of acute myeloid leukemia is different from that of elderly leukemia. The cellular abnormality in cases of elderly acute myeloid leukemia is more pronounced. Features like the presence of an abnormal number of chromosomes in cells, chromosomal abnormality, and abnormality in the nucleus in cells are more common in the elderly. Also, abnormalities in chromosomes 5 and 7 are more common in the elderly with acute myeloid leukemia. Also, elderly leukemia is multidrug-resistant. This is attributed to the involvement of the MDR-1 gene, which is responsible for abnormal functioning and the expression of Pgp (a type of glycoprotein).

What Are the Symptoms of Leukemia in the Elderly?

During the initial phases of leukemia, the symptoms appear slowly and may go unnoticed initially. Also, as the condition advances, the symptoms deteriorate. Occasionally, an individual may harbor the disease for several years without experiencing any apparent symptoms. In the case of acute leukemia, the affected person typically feels unwell to the extent that they seek medical attention. The usual symptoms are;

1. Pain and swelling of the joints.

2. Recurrent episode of fever.

3. Significant loss of weight over a very short duration. Also, weakness and fatigue are observed.

4. Swelling of the lymph nodes in various parts of the body is seen.

5. Recurrent infections can be observed due to a drop in the immune functions.

6. Bruises and pallor can be observed. Microbleeding spots in various portions of the skin are noticed.

7. Enlargements of the spleen can be observed.

The diagnostic process begins with a thorough history and physical examination, which includes chest X-rays and laboratory tests, including blood examination of white blood cells (WBCs), red blood cells (RBCs), and platelet counts. White blood cell counts are often elevated, while platelet and hemoglobin levels are decreased. However, in certain cases, the white blood cell count may be within normal limits or unusually low. Additionally, a bone marrow aspiration or biopsy may be conducted to confirm the diagnosis. Typically, these procedures reveal an increase in bone marrow cell numbers and the percentage of immature cells. A spinal tap may also be performed to determine the extent of leukemia cell dissemination.

What Are the Treatment Options of Leukemia in the Elderly?

The treatment option for acute myeloid leukemia depends on various factors. These factors are the staging of the diseases, the systemic health of the patient, and the presence of different chronic illnesses. In most cases, chemotherapeutic drugs are used to treat such patients. This treatment regime includes an infusion of Cytarabine and an Anthracycline. However, recent studies have shown that, in elderly people such treatment options make it difficult to achieve the desired result due to the mutation of the tp53 gene. Also, leukemia due to antecedent myelodysplastic syndrome (MD- a group of bone marrow disorders) makes it difficult to treat with the help of traditional treatment options. The modern treatment options include;

1. Low-dose cytarabine (Ara-c) is used in combination with other therapies. This drug has cytotoxic effects and inhibits the DNA synthesis of the cancer cells. However, the side effects of this drug are severe, and it is associated with a longer duration of hospital stay.

2. Hypomethylating agents (HMAs) are popular treatment options in such cases. These drugs prevent the formation of tumor cells by suppressing tumor suppressor genes through DNA methylation. The two most commonly used drugs for this purpose are Azacitidine (AZA) and Decitabine (DAC).

3. Gemtuzumab ozogamicin (GO) is a monoclonal antibody. It is formed by humanized CD33 monoclonal antibody conjugated to calicheamicin. This drug acts to cleave the double-stranded DNA.

4. Venetoclax is a drug that inhibits BCL-2 protein. This protein is responsible for which is responsible for anti-apoptotic actions and is responsible for hematologic malignancies. These drugs are often combined with hypomethylating agents (HMAs) and low-dose cytarabine (Ara-c). These combinations are approved by the latest FDA approval as these combination therapies can be effective in cases of TP53, IDH, FMS-like tyrosine kinase 3 (FLT3) or Nucleophosmin-1 (NPM1) mutation.

5. Glasdegib is a new-age drug that prevents the pathways responsible for cancer cell formation in acute myeloid leukemia. However, this drug is responsible for cardiac complications.

6. In modern days, targeted therapies are used to treat elderly individuals. These therapies include the application of drugs like Ivosidenib and Olutasidenib. These two drugs inhibit the mutation of IDH1, which is responsible for acute myeloid leukemia. Enasidenib, another drug belonging to this group, acts on the mutation of IDH2. This drug is effective in the treatment of relapsed cases.

Hematopoietic cell transplantation is advised for patients who are not responding to the traditional forms of treatment. However, such treatment options increase the chances of cytotoxicity and may even cause death.

Conclusion:

Leukemia is a type of blood cancer that affects the elderly population. The common leukemia seen in elderly people is acute myeloid leukemia. Genetic factors and age-related changes in the bone marrow are responsible for such conditions. Different chemotherapeutic drugs are used for treating such conditions.