What is acute lymphocytic leukemia?
Leukemia is an umbrella term that includes many different types of blood cancer, each one of them depending on what cell line is affected. Leukemia is a complex ailment that may include several alterations and severe symptoms that usually require hospitalization until the patient is stable. Acute lymphocytic leukemia, also known as acute lymphoblastic leukemia, is the most common subtype of leukemia, and the most common type of cancer in children.
What is it about? How is it diagnosed and treated? We are going to cover each one of these points in the next paragraphs.
Also known as acute lymphoblastic leukemia or ALL, it is a malignant disease that affects the bone marrow. This is the place where blood cells are formed, starting from lymphoid precursors that become blood cells over time. It features an accelerated growth of lymphoblasts that stay immature and become arrested in their development. As the disease continues and aberrant lymphoblast proliferate further, other blood cells become affected as well.
Even though precursors of red blood cells, neutrophils, and platelets are not affected in acute lymphocytic leukemia, the bone marrow slows down their production to keep on creating aberrant lymphoblasts. Thus, patients will not only have a reduction of fully functional lymphocytes but also a reduction of neutrophils (neutropenia), platelets (thrombocytopenia), and red blood cells (anemia).
Moreover, as it happens in all types of cancer, acute lymphoblastic leukemia may infiltrate to other tissues outside of the bone marrow. The most common sites are lymph nodes, the spleen, and liver, which often results in enlargement of each organ (lymphadenopathy, splenomegaly, and hepatomegaly, respectively).
Causes of acute lymphoblastic leukemia
The majority of studies of acute lymphoblastic leukemia are based on the children population, and investigators have found that many different factors are influencing this type of blood cancer. It is usually a two-step process that includes genetic susceptibility or genetic mutations, and subsequent exposure of the patient to certain infections that trigger exaggerated replication of lymphocyte precursor cells.
In children, acute lymphoblastic leukemia starts in the uterine life, when genes become defective in the bone marrow. This is called a pre-leukemic clone, and it causes leukemia when these genes become activated, which only happens in 1% of the population with a pre-leukemic clone.
With a pre-leukemic clone, the body usually activates leukemia in children with a defective immune response, usually when newborns are not properly exposed to infections during their first weeks. Thus, it is not uncommon to see leukemia in families that are extremely devoted to hygienic measures and cleaning practices.
In adults, ALL does not have identifiable risk factors, and it is not as common as acute myeloid leukemia. It is suspected that certain types of radiations may trigger ALL in adults, as it happened in survivors of the atomic bomb in Hiroshima. Other factors that may be associated with secondary leukemia are other types of cancer, including ovarian cancer, lung cancer, and Hodgkin lymphoma.
Signs and symptoms of acute lymphocytic leukemia
The most relevant signs and symptoms in acute lymphocytic leukemia are as follows:
1. Fever and signs of infection
It is one of the most prevalent symptoms in leukemia, which includes acute lymphocytic leukemia. It is usually a fever of unknown origin that should be investigated thoroughly. Since lymphocytes are affected, and may also give rise to neutrophil alterations, patients are susceptible to infection, but other signs are not always prevalent, and patients will only display fever until the doctor finds out its cause.
2. Anemia and pallor
As noted above, acute lymphocytic leukemia not only affects lymphocytes but may also cause a reduction in other cell lines, including erythrocytes (red blood cells). As such, these patients have diluted blood that does not contain as much hemoglobin as it should. This reduction in hemoglobin level is called anemia, and one of the most frequent signs is pallor. Hemoglobin is what gives its natural red pigment to our blood, especially when it is fully oxygenated. Thus, insufficient hemoglobin in the blood leads to a change of color in the blood and the skin.
3. Hemorrhagic manifestations
Another cell line that is commonly taken in acute lymphocytic leukemia is platelets. These cells continuously circulate throughout the body searching for tears and scratches in the skin, mucosa, or inside the blood vessels. They are essential for coagulation and wound healing. Thus, patients with a reduction in their platelets will have diverse manifestations of hemorrhage, which typically include petechial red dots throughout the body. In some cases, patients develop larger areas of subcutaneous hemorrhage as a result of minor trauma and non-traumatic pressure in the skin.
4. Enlarged lymph nodes and organs
As noted before, aberrant lymphocytes not only stay in the blood marrow and the blood. They migrate to other organs and deposit in lymph nodes, the spleen, and the liver. As they do so, lymph nodes become swollen, and your doctor may also detect an increase in the size of your liver and spleen. This is detected either by physical examination or imaging studies when it is a mild enlargement.
5. Skin rash
There are different types of rash associated with acute lymphocytic leukemia. They can be either hemorrhagic (as noted above), infectious, or associated with leukemia itself. Infectious rash is usually caused by viruses and may also respond to fungal infections. We can also have infiltration of aberrant lymphocytes in the skin, resulting in additional sources of skin rash.
Diagnosis
Diagnosing leukemia is not always easy, but doctors need to pay extra attention to the signs and symptoms noted above, and their combination. Patients usually come to the doctor with signs and symptoms of infiltration in various organs or abnormal production of bone marrow elements.
The most common symptom is fever with no other sign of infection. These patients require an urgent assessment to treat any infection because they tend to be fatal in the late stages of the disease.
A series of tests are made for diagnosis, which includes a complete blood cell count, and there should be an emphasis on physical examination. The most important tests are as follows:
• Complete blood count
• Peripheral smear
• Fibrinogen, prothrombin time, and activated partial thromboplastin time
• Renal and liver function tests
• Chest radiography and chest computed tomography depending on the symptoms
• Blood cultures and bone marrow aspiration biopsies when there is a high suspicion, and doctors need to have a definite diagnosis.
In blood tests, patients usually have a neutrophil count that is lower than the average, and the total white blood cell count may be either normal, elevated, or lower than normal. Another common finding is anemia (a reduction of hemoglobin in the blood), which correlates with symptoms such as pallor, dizziness, palpitations, and difficulty breathing.
Physical examination typically includes lymphadenopathy (enlarged lymph nodes), and some patients may even have a mediastinal mass that is detected through imaging studies. Another manifestation of the disease is bone pain, which typically results from the infiltration of cells in the bone tissue.
In advanced cases, patients may even come to the emergency room with an altered mental status and respiratory distress. That only happens when there is an excessive number of lymphoblasts in the blood.
Treatment
A specialist on the field should treat acute lymphoblastic leukemia. These patients have very especial needs and may require supportive care through transfusion of blood products, hydration, and isolation to prevent infections. After ALL is diagnosed, patients should stay hospitalized to start the first doses of chemotherapy as soon as possible. This is called induction chemotherapy, and include both chemotherapeutic drugs and steroid drugs depending on each individual patient.
Then, consolidation therapy is started to give patients an increased chance of survival after 3 years. When patients improve their condition. Another option would be a transplant, which is why not many patients need maintenance therapy.
In treating ALL, we should not only care about the number of aberrant lymphocytes but also other diseases that may be triggered by leukemia. Since meningeal leukemia is very prevalent in patients with a relapse, doctors may choose to administer intrathecal chemotherapy to prevent the involvement of the central nervous system. We should also reduce the risk of infection through antibiotic and antifungal prophylaxis, and keep an eye on the blood values of patients to guide supportive therapy.
Even when patients are stable, it is essential to maintain long-term monitoring as an outpatient. Some of them have a higher risk of relapse and should be treated with itraconazole and antifungal therapy while others have a higher risk of Pneumocystis jiroveci pneumonia, and should be treated with trimethoprim-sulfamethoxazole.
References
Brisson, G. D., Alves, L. R., & Pombo-de-Oliveira, M. S. (2015). Genetic susceptibility in childhood acute leukaemias: a systematic review. Ecancermedicalscience, 9.
O’Donnell, M. R., Tallman, M. S., Abboud, C. N., Altman, J. K., Appelbaum, F. R., Arber, D. A., … & De Lima, M. (2017). Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network, 15(7), 926-957.
O’Donnell, M. R., Abboud, C. N., Altman, J., Appelbaum, F. R., Arber, D. A., Attar, E., … & Lancet, J. (2012). Acute myeloid leukemia. Journal of the National Comprehensive Cancer Network, 10(8), 984-1021.
Kantarjian, H. (2016). Acute myeloid leukemia—major progress over four decades and glimpses into the future. American journal of hematology, 91(1), 131-145.