Overview of Acute Lymphoblastic Leukaemia in Teenagers and Young Adults
Acute lymphoblastic leukaemia (ALL) is an aggressive cancer of the blood and bone marrow caused by the uncontrolled proliferation of immature lymphoid cells, known as lymphoblasts. While ALL is most common in young children, it also affects teenagers and young adults (TYA), typically aged 15–39, where it often presents with different biological characteristics and treatment responses compared to childhood ALL.
In this age group, ALL can be more challenging to treat, and outcomes are historically less favorable than in younger children, though survival rates have improved significantly with pediatric-inspired treatment protocols. Early diagnosis and aggressive therapy are key to achieving remission and long-term survival.
Commonly Associated with Acute Lymphoblastic Leukaemia in Teenagers and Young Adults
ALL in teenagers and young adults is associated with several risk factors and conditions, including:
- Age 15–39 years, with a peak in late adolescence and early adulthood
- Male gender, as ALL is slightly more frequent in males
- Genetic abnormalities, such as the Philadelphia chromosome (t[9;22]), MLL rearrangements, or iAMP21
- Inherited genetic syndromes, including Down syndrome and Li-Fraumeni syndrome
- Previous exposure to radiation or chemotherapy
- Environmental exposures to chemicals like benzene
- Obesity, which has been linked to increased risk and poorer outcomes
Causes of Acute Lymphoblastic Leukaemia in Teenagers and Young Adults
The precise cause of ALL remains unclear, but it develops due to genetic mutations in lymphoid progenitor cells that lead to uncontrolled growth and impaired differentiation. Factors contributing to these mutations include:
- Chromosomal translocations (e.g., BCR-ABL1 fusion from t[9;22]) that activate oncogenes
- Inherited predisposition to DNA damage or impaired immune regulation
- Prior cancer therapies, which may cause DNA mutations
- Environmental exposures such as ionizing radiation or toxic chemicals
- Spontaneous DNA errors during normal immune cell development
In teenagers and young adults, the disease may exhibit different biological features from childhood ALL, often involving more aggressive subtypes and a higher prevalence of high-risk genetic lesions.
Symptoms of Acute Lymphoblastic Leukaemia in Teenagers and Young Adults
Symptoms often develop rapidly over weeks and result from bone marrow failure and infiltration of leukemic cells into other organs. Common signs include:
- Anemia symptoms: Fatigue, pallor, dizziness, shortness of breath
- Infection susceptibility: Recurrent fevers, sore throats, and infections
- Bleeding tendencies: Easy bruising, petechiae, gum bleeding, nosebleeds
- Bone and joint pain: Especially in long bones and joints
- Swollen lymph nodes, liver, or spleen
- Unexplained weight loss and night sweats
- Mediastinal masses, particularly in T-cell ALL, causing chest pain or breathing difficulty
- Neurological symptoms: Headaches, nausea, or vision changes if the central nervous system is affected
Teenagers and young adults may present later in the disease course than children, sometimes delaying diagnosis.
Exams & Tests for Acute Lymphoblastic Leukaemia in Teenagers and Young Adults
Diagnosis involves detailed clinical, hematologic, and molecular testing:
- Complete blood count (CBC): Often reveals anemia, thrombocytopenia, and abnormal white blood cells.
- Peripheral blood smear: Shows circulating lymphoblasts.
- Bone marrow aspiration and biopsy: Confirms diagnosis with >20% blasts.
- Immunophenotyping (flow cytometry): Differentiates B-cell from T-cell ALL and guides treatment.
- Cytogenetic and molecular tests: Identify chromosomal abnormalities (e.g., BCR-ABL1, MLL rearrangements) crucial for risk stratification.
- Lumbar puncture: Checks for central nervous system involvement.
- Imaging (chest X-ray/CT): Detects mediastinal masses, especially in T-cell ALL.
Treatment of Acute Lymphoblastic Leukaemia in Teenagers and Young Adults
Treatment in teenagers and young adults has evolved significantly, with pediatric-inspired regimens now considered the standard of care due to improved outcomes compared to traditional adult protocols. Therapy is typically multi-phased:
1. Induction Therapy:
- Goal: Achieve complete remission by eradicating leukemic cells.
- Regimen: Combination chemotherapy (vincristine, corticosteroids, anthracyclines, asparaginase).
2. Consolidation (Intensification) Therapy:
- Goal: Eliminate residual disease and reduce relapse risk.
- Regimen: High-dose chemotherapy ± targeted agents.
3. Maintenance Therapy:
- Goal: Sustain remission over 2–3 years.
- Regimen: Low-dose oral chemotherapy (methotrexate, mercaptopurine).
4. Central Nervous System (CNS) Prophylaxis:
- Intrathecal chemotherapy ± cranial irradiation to prevent CNS relapse.
5. Targeted Therapies and Immunotherapies:
- Tyrosine kinase inhibitors (e.g., imatinib, dasatinib) for Philadelphia chromosome-positive ALL.
- Monoclonal antibodies (e.g., blinatumomab, inotuzumab) and CAR T-cell therapy for relapsed/refractory disease.
6. Stem Cell Transplantation:
- Considered for high-risk patients or those with relapsed disease.
Supportive care, including infection prevention, blood transfusions, and psychological support, is essential. Fertility preservation discussions should occur before treatment initiation due to potential impacts on reproductive health.
Source
- Stock W, et al. “Acute lymphoblastic leukemia in adolescents and young adults.” Hematology Am Soc Hematol Educ Program 2010; 2010(1):21–29.
- Boissel N, et al. “Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults?” Blood 2003; 102(2):427–434.
- National Cancer Institute. “Adolescent and Young Adult Acute Lymphoblastic Leukemia Treatment (PDQ®) – Health Professional Version.” NCI, 2024.
