Understanding Leukemia: Types, Causes, Screening, and Treatment Options By Zhang Chenxi
Introduction
Leukemia is a type of cancer that is found in the bone marrow and results from the uncontrolled production of abnormal white blood cells, deviating from its usual function of fighting foreign influences in the body, as well as inhibiting the bone marrow from producing healthy red blood cells and white blood cells. Leukemia can be broadly classified into two categories: acute leukemia and chronic leukemia, each with distinct characteristics. The former progresses rapidly, while the latter worsens slowly with its symptoms remaining undetected for years. As one of the most common cancers in the world, leukemia can affect any demographic with varying types targeting certain age groups more prominently.
Types of Leukemia
Acute Lymphocytic Leukemia (ALL)
Acute lymphocytic leukemia (ALL) is known for being the most common form of leukemia targeting children. It mainly affects the production of lymphocytes, which is a type of white blood cell that is premature. This type of white blood cell proliferates in the body, causing the different types of healthy blood cells in the body to fall below normal levels. For instance, anemia is a result of the shortage of red blood cells to carry oxygen in the body, hence the patient suffers from symptoms of fatigue and shortness of breath. The shortage of platelets also causes blood to clot more slowly, resulting in excessive bleeding. A symptom uniquely associated with ALL is the swelling of the thymus. According to the National Cancer Institute of the United States, the five-year relative survival rate for ALL patients is 69.9%.
Acute Myelogenous Leukemia (AML)
Similar to ALL, the other type of acute leukemia, acute myelogenous leukemia (AML) is the most typical form of aggressive leukemia in adults. While it is quite similar to ALL in the way in which it affects the levels of other healthy blood cell levels in the body, AML causes the body to produce excess numbers of myeloid cells. Both types of acute leukemias have similar symptoms, resulting in a weaker immune system. The five-year relative survival rate of AML patients is 29.8%.
Chronic Lymphocytic Leukemia (CLL)
Known as the most prevalent type of slow-growing leukemia, chronic lymphocytic leukemia (CLL) commonly affects the elderly the most. Unlike acute leukemia, leukemia cells in the body build up slowly, and the white blood cells can mature partially. It often takes up to years before chronic leukemia starts to cause problems in the body, though it can be harder to cure than acute leukemia. Furthermore, the progressive nature of CLL means that most patients do not possess any symptoms at the point of diagnosis, and it can only be detected through blood tests including high numbers of lymphocytes. The symptoms of CLL are often vague, such as fatigue, weight loss, and chills, which can often be wrongly diagnosed as other diseases. The five-year relative survival rate of CLL patients is 85%, which is higher given the time for the disease to deteriorate.
Causes and Risk Factors
In current research, the definite cause of leukemia is not known. However, there are certain common risk factors that make people more vulnerable to developing leukemia. Like any other cancer, exposure to chemicals such as benzene and formaldehyde puts patients at a higher risk of developing acute leukemia or CLL. Furthermore, genetic disorders like Down syndrome and Bloom syndrome can also increase one’s susceptibility to developing leukemia. Specifically for CML, the abnormal ‘Philadelphia’ chromosome which is found in the leucocytes of leukemia patients causes the mutations of leukemia cells. This is often linked to exposure to intense radiation.
In addition, there are certain inexplicable demographic factors that put an individual at greater risk of developing leukemia. Males develop leukemia more commonly than females do, though the exact cause is not yet known. Age also increases one’s risk of developing chronic leukemia and the weakened immune system causes the relative survival rates at a higher age group to decrease.
Screening for Leukemia
In the preliminary stage of diagnosis, a physical examination is required to detect for presence of swollen lymph nodes to detect high levels of lymphocytes, or bleeding gums this can be an indication of low platelet levels. For a more comprehensive diagnosis to be done, a blood test is required to test for levels of white blood cells, red blood cells, and platelets to verify if the white blood cell count is higher than normal. Flow cytometry, peripheral blood smear, and bone marrow biopsy are methods used to detect the presence of leukemia cells, which are an indicator of the specific type of leukemia developed. Other forms of screening in essential organs like the chest and spinal cords may be ordered to observe the progress of leukemia. Leukemia cells in the central nervous system are often harder to treat subsequently.
Existing Treatment Options
Based on the doctor’s diagnosis, the treatment that a leukemia patient receives is contingent on their age, health, as well as the type of leukemia they suffer from. As there is no definite cure for leukemia, the patient receives treatment that is an amalgamation of the common methods below to increase their chances of survival.
Chemotherapy
Chemotherapy for Leukemia typically utilizes cytotoxic drugs that are circulated throughout the body via the bloodstream to induce apoptosis (programmed cell death) in labile cells. Common chemotherapy drugs for Leukemia include hydroxycarbamide for Chronic Myelogenous Leukemia and Vincristine (Marqibo), Daunorubicin (Daunomycin), and PEG-L-asparaginase (Oncaspar) for Acute Lymphocytic Leukemia, taken in the form of oral capsules or intravenously, which reduces white blood cell count to slow the progress of cancer cell metastasis, shrink tumor sizes in preparation for radiation treatments and relieve cancer-related symptoms.
On the other hand, while chemo drugs efficiently lower white blood cell count in leukemia patients, their drug action is non-specific and can induce apoptosis in other labile cells (cells that undergo rapid cellular mitosis) such as skin cells, intestinal cells, bone marrow cells, red blood cells, and hair follicle stem cells. Common side effects of chemotherapy include Fatigue, Hair Loss, Loss of Appetite, and Nausea. Reduction of platelets may also lead to patients becoming more prone to bruising and bleeding while lowering of white blood cell count can increase the risk of serious infections. In view of this, typical chemotherapy routines are conducted with 7-day infusions followed by 3 treatment-free weeks where patients are monitored for possible side effects due to the treatment.
Peripheral Blood Stem Cell/Bone Marrow Transplantation
The other procedure for leukemia is the donation of healthy stem cells to the patient’s bone marrow, often from another donor, known as allogeneic treatment, or the patient’s own body, known as autologous treatment. Since hematopoietic stem cells which turn into healthy blood cells are damaged in leukemia, hematopoietic stem cells are transplanted to restore the body’s ability to create normal blood cells. Furthermore, cancer treatment can also damage the stem cells and immune system. Therefore, for patients who wish to receive autologous treatment, their stem cells have to be removed prior to receiving treatment. For patients who wish to receive allogeneic treatment, it is essential that there is a match between the stem cells of the donor and the stem cells of the patient. Otherwise, the patient may suffer from the side effect of Graft-versus-host disease (GVHD), in which the donor cells attack the immune system and may cause serious health complications.
Radiation Therapy
Radiotherapy for leukemia uses high levels of radiation to kill the leukemia cells in the body. It is used to treat leukemia which has spread out of the bone marrow to more essential parts of the body, such as spinal fluids or the brain. It can also alleviate the pain in an area of the bone where leukemia cells have spread to. A common type of radiation therapy is the external beam radiation therapy, which utilises radiation from an external machine to target specific cancer cells. In other cases, a total body irradiation is carried out before a transplantation to reduce leukemia cells in the body. While the process itself is painless, there are notable side effects of the radiation on body such as hair loss, burnt skin and physical discomfort like nausea, vomiting and diarrhea.
TKI Therapy
Tyrosine Kinase Inhibitors often come in the form of oral tablets prescribed in a patient-specific manner. It is a form of targeted therapy that selectively attacks specific mutant-BCR-ABL1 protein while avoiding possible side effects to normal cells. For the case of Chronic Myelogenous Leukemia, TKI drugs are often prescribed to patients as the First-line treatment via its downregulation mutant-BCR-ABL1 oncogenes responsible for the uncontrolled growth of CML Cells. Presently approved TKI drugs include First Generation Imatinib mesylate (Gleevec), Second Generation Dasatinib (Sprycel), Nilotinib (Tasigna), and Bosutinib (Bosulif); other approved TKI medication for patients with the T315I mutation include Third Generation Asciminib (Scemblix) and Ponatinib (Iclusig).
However, clinical trials have revealed that long-term prescriptions of TKI-drugs have led to patients developing drug resistance due to further mutations in the BCR-ABL1 Kinase domain, with others experiencing high levels of intolerance (severe side-effects) towards the drugs leading to the discontinuation of long term treatments, necessitating the follow-up of Second-line treatment options like Chemotherapy and Stem-Cell Transplants.
Conclusion/ Analysis
Developments and breakthroughs in leukemia mainly revolve around developing new forms of treatments to curb the spread of leukemia cells in the body. Newer forms of treatment include the pill Revumenib, which has eradicated the cancer in one-third of the participants in the clinical trial, even seeing complete disappearance of the leukemia cells from the bone marrow of the participants. Such a result makes scientists extremely hopeful of a new possible cure for leukemia, as it is possibly the biggest breakthrough for leukemia research in the past decade. Meanwhile, other forms of existing treatments are also being fine-tuned to reduce the possible side effects, especially for children who suffer from ALL.
While the scientific community pools their collective knowledge to come up with inventive treatments for leukemia patients, we can do our part together too in saving a life. The donation of blood stem cells has little implications on the donor’s own long-term health, but it can mean so much to a patient suffering from terminal leukemia – a scintillating glimmer of hope and a rejuvenation of their lives all over again. It does not take much; register to be a blood stem cell donor and go to www.bethematch.org to order a collection kit which will be promptly sent to your house. The choice is yours and be the change you want to see in the world.
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