Acute lymphoblastic leukemia (ALL) is a malignancy involving the uncontrolled proliferation of immature lymphocytes, leading to the replacement of bone marrow elements and other lymphoid organs. In the U.S., ALL is the most widespread form of leukemia and cancer among children. The understanding of the biology of ALL has advanced significantly over the past few decades, leading to notable advancements in diagnosis, therapy, and monitoring. Since the introduction of chemotherapy, ALL has served as a testing ground for novel strategies that can be applied to cancer in general.
Etiology
Acute lymphocytic leukemia’s cause is unknown, but environmental factors like benzene exposure and chemotherapy can increase the risk. Genetic studies show somatic variants and rare mutations in genes like ARD5B, IKZF1, and CDKN2A are associated with increased risk. No screening programs exist for childhood. There are no screening programs set up to check for acute lymphoblastic leukemia in children, and the disease is not thought to be inherited.
Pathophysiology
It has been proposed that DNA damage leads to an uncontrolled growth and dissemination of lymphoid cells throughout the body, which in turn produces acute lymphocytic leukemia. The accumulation of platelets and lymphocytes in the spleen and liver causes splenomegaly and hepatomegaly; the spleen reacts to the abnormal white blood cells by working to eliminate them from circulation.
Signs and Symptoms
Acute lymphocytic leukemia (ALL) symptoms are nonspecific and difficult to distinguish from childhood diseases. Over half of children have palpable liver, spleen, pallor, fever, or bruising. Patients often experience night sweats, bruising, skin pallor, lymphadenopathy, weakness, weight loss, hepatosplenomegaly, difficulty breathing, superior vena cava syndrome, bone pain, mental changes, and peripheral blood cell abnormalities.
Current Survival Rates for Acute Lymphoblastic Leukemia
Over 65 percent of people with ALL survive for five years or more after diagnosis, with younger individuals generally having a better prognosis. Younger individuals, aged 15-39, have a survival rate of almost 90%, while those aged 40 or older have a survival rate of around 20%. Age affects treatment response.
Factors Affecting ALL Prognosis:
Good prognostic criteria include:
- Under 30 years old
- No cytogenetic anomalies
- less than 30,000 WBCs
- Total remission in four weeks
- Children with 51–65 chromosomes have high hyperdiploidy (t (12; 21) (p13; q22).
Among the poor prognostic variables are:
- Over 60 years old
- Abnormal cytogenetics are present (t (9:22), t (4:11).
- No remission in four weeks
- B-cell precursors greater than 100,000
Related: Early Signs of Leukemia in Blood Work
Advances in Treatments for Improved Outcomes
- Chemotherapy uses drugs to stop cancer cell growth. Systemic chemotherapy enters the bloodstream, while intrathecal chemotherapy reduces leukemia cell spread to the brain and spinal cord.
- Radiation Therapy: Uses high-energy X-rays or radiation to kill cancer cells. External radiation therapy treats ALL that has spread to the brain and spinal cord. Total-body irradiation prepares for a stem cell transplant.
- Chemotherapy with Stem Cell Transplant: This treatment replaces blood-forming cells; reinfused stem cells grow into the body’s blood cells.
- Targeted Therapy: Identifies and attacks specific cancer cells, with biomarker tests for response prediction.
- Immunotherapy: Helps the immune system fight cancer; uses blinatumomab, inotuzumab ozogamicin, and CAR T-cell therapy.
Summary
Acute leukemia management involves an interprofessional team including oncologists, internists, infectious disease experts, and hematologists. Primary care providers and nurse practitioners monitor patients for infections, coagulation dyscrasias, and relapse. Team conferences are held during treatment.
References:
Pagliaro, L., Chen, S. J., Herranz, D., et al. (2024). Acute lymphoblastic leukaemia. Nature Reviews Disease Primers, 10(41). https://doi.org/10.1038/s41572-024-00525-x.
Puckett, Y., & Chan, O. (2023). Acute lymphocytic leukemia. In StatPearls. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK459149/.
