Leukemia is a type of blood cancer that starts in the bone marrow, where blood cells are made. Acute lymphoblastic leukemia (ALL) is a specific type of leukemia that affects the lymphocytes, a type of white blood cell. ALL progresses rapidly and treatment is needed right away. With modern treatments, many patients with ALL can be cured, but not all cases of ALL are curable.
What is ALL?
ALL is a cancer of the lymphocytes, a type of white blood cell made in the bone marrow that is part of the immune system. In ALL, the bone marrow makes many abnormal, immature lymphocytes, which are called lymphoblasts. These lymphoblasts crowd out the healthy blood cells in the bone marrow, leading to anemia, bleeding problems, and infections. The abnormal lymphocytes also spread to the bloodstream and can then spread to other parts of the body including the lymph nodes, liver, spleen, central nervous system, and testicles.
ALL is the most common type of leukemia in children, but it can also occur in adults. It is a fast-growing leukemia that needs treatment right away. With treatment, many patients can be cured, especially children. Overall survival rates for children with ALL are around 90%. For adults, the cure rates tend to be lower, between 30-40% for those under 60 years old.
What causes ALL?
The exact causes of ALL are not fully understood. However, there are some known risk factors that can increase the chances of developing ALL:
- Genetic abnormalities – Certain genetic changes or syndromes can increase ALL risk including Down syndrome, ataxia telangiectasia, Bloom syndrome, neurofibromatosis, Klinefelter syndrome, Fanconi anemia, and Li-Fraumeni syndrome.
- Radiation exposure – Higher levels of radiation exposure from medical treatments, nuclear disasters, or other sources increase ALL risk slightly.
- Chemical exposure – Certain chemicals like benzene and previous chemotherapy drugs may increase the risk of ALL.
- Prior cancer treatment – Children with some other types of cancer have a higher risk of developing ALL later on.
- Age – ALL is most common in young children under 5 years old.
However, in many ALL cases, there are no clear risk factors identified. More research is needed to fully understand the causes and risk factors for ALL.
What are the symptoms of ALL?
The symptoms of ALL result from having too many abnormal lymphocytes and not enough healthy blood cells. Common symptoms can include:
- Fatigue or weakness – Due to anemia from lack of red blood cells
- Bleeding or bruising easily – Due to low platelets
- Frequent infections – From lack of normal white blood cells
- Fever
- Bone or joint pain
- Swollen lymph nodes
- Abdominal pain or fullness
- Coughing or breathlessness
- Headaches
- Rashes
The symptoms may be vague at first and resemble other common illnesses. Seeking prompt medical attention for persistent unexplained symptoms is important, as early diagnosis and treatment of ALL leads to better outcomes.
How is ALL diagnosed?
If ALL is suspected based on symptoms and a physical exam, several tests will be done to confirm the diagnosis:
- Blood tests – A complete blood count can detect abnormalities in white blood cells, hemoglobin and platelets.
- Bone marrow aspiration and biopsy – A sample of bone marrow is taken from the hip bone and examined under a microscope. This test can detect leukemia cells in the bone marrow.
- Lumbar puncture (spinal tap) – A sample of cerebrospinal fluid is taken from the spine and examined for leukemia cells, which can spread to the central nervous system.
- Imaging tests – Ultrasound, CT scan or MRI may detect cancer spread to lymph nodes, liver or spleen.
- Immunophenotyping – Testing identifies certain proteins on the surface of leukemia cells.
- Cytogenetic analysis – Chromosomes of leukemia cells are examined for genetic abnormalities.
These test results confirm the diagnosis of ALL and help classify the subtype of ALL and determine treatment options.
ALL classification systems
There are a few different classification systems used for ALL to determine the subtype:
Cell type
ALL starts in early forms of lymphocytes. There are 2 main cell types:
- B-cell ALL – Starts in early B cell lymphocytes, about 85% of childhood and 75% of adult ALL cases
- T-cell ALL – Starts in early T cell lymphocytes, about 15% of childhood and 25% of adult ALL cases
Genetic abnormalities
Specific genetic changes in the chromosomes of the leukemia cells are identified. Some common abnormalities include:
- Hyperdiploidy – Extra chromosomes
- Hypodiploidy – Missing chromosomes
- Philadelphia chromosome – Translocation between chromosomes 9 and 22
- MLL gene rearrangement
- TEL-AML1 fusion
- E2A-PBX1 fusion
Risk level
Based on test results, ALL is classified into a risk level:
- Standard risk – Younger than 50 years, lower white blood cell count, no genetic abnormalities. About 85% of children and 50% of young adults.
- High risk – Older age, high white blood cell count, genetic changes like Philadelphia chromosome. About 15% of children and 50% of young adults.
The risk level helps determine appropriate treatment intensity.
How is ALL treated?
Treatment for ALL has three main phases: induction therapy, consolidation therapy, and maintenance therapy. The goal is to get the leukemia into remission and then continue treatment to prevent recurrence.
Induction therapy (4-6 weeks)
The first phase uses chemotherapy drugs to kill leukemia cells and restore normal blood cell levels. Types of drugs used may include:
- Vincristine
- Doxorubicin
- Dexamethasone
- Asparaginase
- Cyclophosphamide
- Cytarabine
- Methotrexate
- Etoposide
Up to 3-4 drugs are used together. For high-risk ALL, more intense regimens may be used. Radiation to the brain and/or spinal cord may be done to prevent spread to the central nervous system. About 95% of children and 75-80% of adults will reach remission after induction therapy.
Consolidation therapy (several months)
This phase uses chemotherapy to destroy any remaining leukemia cells in the body. Usually the same drugs are used as in induction therapy. Those with standard risk ALL may receive 2-4 cycles of consolidation chemo. High risk patients receive more cycles with more drug combinations. Additional radiation may be used. Consolidation therapy reduces the chance the ALL will come back.
Maintenance therapy (2 years)
During this phase, chemotherapy is given in lower doses over a prolonged period to prevent recurrence of leukemia. Drugs like 6-mercaptopurine, methotrexate, vincristine and prednisone are used. Spinal taps to deliver chemo into the spinal fluid may be done periodically. Maintenance therapy lasts about 2 years for most patients.
Stem cell transplant
Some high risk patients may undergo a stem cell transplant as part of consolidation therapy. This intensive treatment first uses high dose chemo (sometimes radiation) to destroy the remaining ALL cells, then the patient receives a transplant of blood-forming stem cells to restore their bone marrow function. Stem cells may come from a donor or the patient’s own cells. Stem cell transplant has more risks of serious side effects but may reduce the chance of recurrence in high risk leukemia.
Targeted therapy
Newer targeted drugs that specifically attack cancer cells while sparing normal cells are now being used in some ALL patients. These include:
- Tyrosine kinase inhibitors like imatinib – for Philadelphia chromosome positive ALL
- Blinatumomab – Bispecific monoclonal antibody that enables the immune system to recognize and attack ALL cells
- Inotuzumab ozogamicin – Antibody drug conjugate that targets CD22 protein on leukemia cells
- Chimeric antigen receptor (CAR) T-cell therapy – Patient’s own T cells are genetically engineered to target leukemia cells
These types of targeted therapies are allowing more personalized treatment based on the specific ALL genetics.
What is the prognosis and survival rates for ALL?
The prognosis for ALL depends on several factors, including age, leukemia cell type, genetics, initial white blood cell count, and how well the leukemia responds to the initial phases of treatment.
Some approximate overall survival rates by risk group:
| Risk Group | Children | Adults under 60 |
|---|---|---|
| Standard risk ALL | 90-95% | 50-70% |
| High risk ALL | 80-90% | 35-50% |
Survival rates have improved dramatically over the past several decades thanks to advances in chemotherapy regimens, better monitoring for recurrence, improved supportive care, and the use of stem cell transplants. Childhood ALL was once fatal in nearly all cases, but now has overall survival over 90%. However, outcomes in adult ALL remain somewhat lower.
With current treatments, 60-90% of all ALL patients will reach a long-term first remission. However, there remains a risk of relapse in which the leukemia returns after treatment. This risk is 15-20% in children and 40-50% in adults. Second remissions are more difficult to achieve, so preventing relapse during the first remission is critical.
What are the side effects of ALL treatment?
Because the necessary treatments for ALL are quite intensive, there are acute and long-term side effects possible:
Acute side effects
- Nausea, vomiting – Common chemo side effect
- Hair loss – Temporary from intensive chemo
- Fatigue – From anemia and treatment intensity
- Bleeding/bruising – Due to low platelet counts
- Mouth sores – From chemotherapy
- Diarrhea – Caused by some treatments
- Infections – From low white blood cell counts
Long-term side effects
- Infertility – Chemotherapy impairs reproductive cells
- Growth issues – In children treated at young ages
- Learning problems – Caused by treatments affecting the brain
- Heart problems – Resulting from some drugs or radiation therapy
- Kidney issues – From certain medications
- Lung problems – Pulmonary fibrosis from medications
- Bone issues – Osteoporosis risk from steroids
- Cataracts or other vision changes – Due to steroids
- Hormonal issues – Resulting from effects on endocrine glands
- Neuropathy – Nerve damage from drugs affecting nervous system
- Fatigue
- Secondary cancers – Slightly increased risks later in life
Monitoring and prompt management of any side effects is important. Before treatment, discuss options like egg/sperm banking, ovarian transposition surgery, hormone replacement, and learning support services that may help reduce long-term effects.
What happens after ALL treatment?
Regular monitoring is extremely important after finishing ALL therapy. Frequent complete blood counts, bone marrow evaluations, and possibly lumbar punctures should be done to watch closely for any signs of leukemia recurrence. Monitoring is most frequent in the first 1-2 years after treatment when relapse risk is highest.
Routine cancer screening should be continued based on the treatment received – for example, breast cancer or skin cancer screening after radiation therapy. Monitoring for late effects and screening for other health issues related to previous treatments should be carried out under the direction of a primary care doctor.
After successful ALL treatment, leading an active, healthy lifestyle can help manage any long-term side effects. Maintaining follow-up care and reporting any concerning symptoms to your doctors can allow prompt treatment of any leukemia recurrence or late effects if they arise.
What is the latest research for ALL treatment?
Key areas of current ALL research include:
- New targeted therapies – More antibody and immunotherapy drugs are being studied to improve effectiveness and reduce toxicity compared to standard chemo drugs. These include blinatumomab, inotuzumab ozogamicin, CAR T-cell therapy, and bispecific T-cell engagers.
- Minimal residual disease monitoring – Improved testing methods to detect very low levels of residual leukemia cells after treatment may help guide further therapy and prevent relapse.
- Genetic studies – Gene sequencing of leukemia cells helps identify prognostic factors and new potential treatment targets.
- Supportive care – Studies on growth factors, transfusions, and antibiotics aim to improve blood counts and reduce infection risks during treatment.
- Reduced intensity chemo – For older adults, using lower doses, fewer drugs, or shorter durations may reduce side effects.
- Survivorship care – Research on preventing, detecting, and managing long-term effects of treatment.
By building on past treatment advances and discoveries, current research continues to move toward the ultimate goal of curing all patients with ALL while reducing treatment side effects as much as possible.
Conclusion
Major progress has been made in ALL treatment, dramatically improving the cure rate from near zero to up to 90% in children with current standard chemotherapy regimens and other therapies. However, ALL remains a serious diagnosis with intense demands of treatment. Not every patient can yet be cured of ALL, especially higher risk patients who relapse or don’t respond well to initial treatment.
Continued research to fine-tune therapy, develop targeted drugs with less toxicity, detect recurrence earlier, and improve access to care will help working toward the ideal future where every ALL patient can be cured, regardless of age or disease characteristics. Staying up-to-date on the latest advances provides hope that this dream could become reality soon.