In most cases of ALL, the cause is unknown, but several risk factors have been identified, including:

• Being a child or an adult over age 50
• Male gender
• Radiation exposure (e.g., radiation therapy, X-rays, nuclear radiation)
• Past chemotherapy treatment
• Having certain genetic syndromes including Down syndrome, neurofibromatosis type 1, Bloom syndrome, and ataxia-telangiectasia, among others
• Having inherited certain gene or chromosome variants
• Certain viral infections (e.g., Epstein-Barr Virus, Human Immunodeficiency Virus (HIV))
• Pesticide exposure

Symptoms of ALL may include:

• Feeling tired
• Weakness
• Fever and/or night sweats
• Shortness of breath
• Easy bruising and/or bleeding
• Nosebleeds and/or bleeding gums
• Unintentional weight loss/loss of appetite
• Pale skin
• Tiny red spots on skin (known as petechiae)
• Abdominal pain and swelling
• Swollen lymph nodes
• Bone and/or joint pain
• Frequent infections

To diagnose ALL, doctors will review the patient’s medical history, perform a physical exam, and order additional tests.

The doctor will ask about symptoms and risk factors for ALL. During the physical exam, he or she will feel the lymph nodes and abdomen to check for swelling, and also examine the skin for signs indicative of ALL. For men, a testicular exam may be performed.

To confirm a diagnosis, the following additional tests may be ordered:

• Blood tests. A complete blood count (CBC) and a peripheral blood smear may be ordered. The CBC test is used to measure the numbers of different types of blood cells. In the blood smear, blood is smeared on a slide then examined under a microscope to check for abnormalities.
• Bone marrow aspiration and biopsy. In a bone marrow aspiration, a doctor inserts a needle into the hip bone and uses it to remove a fluid sample from the bone marrow. For a bone marrow biopsy, a doctor uses a needle to remove a small piece of the spongy bone marrow from the hip bone. These procedures are often performed together. A pathologist examines the tissue samples under a microscope to check for the presence of cancer cells.
• Molecular and genetic testing. These tests help doctors establish the type of leukemia cells involved and their genetic characteristics. Determining the specific type of ALL helps doctors choose the best course of treatment for each patient.
  • Cytogenetic testing. In cytogenetic testing, doctors examine leukemia cells under a microscope to check for chromosome abnormalities.
  • Molecular genetic testing. Other genetic tests can help determine if the leukemia cells have any genetic changes linked to different types of ALL.
  • Immunophenotyping. Lab tests, including flow cytometry and immunohistochemistry, are used to identify molecular markers on ALL cells.
    
Molecular and genetic testing are also employed in tracking very low levels of leukemia cells, called “measurable residual disease” or MRD, during the course of treatment.

Additional tests may be used to determine whether and how ALL is affecting the central nervous system, lymph nodes, or other parts of the body.

• Lumbar puncture (spinal tap). A spinal tap is used to determine if ALL cells have spread to the tissues around the brain and spinal cord.
• Lymph node biopsy. In this procedure, a surgeon will remove a lymph node or part of a lymph node. A pathologist then analyzes the tissue under a microscope. 
• Imaging tests. Imaging tests such as computed tomography (CT) scans, magnetic resonance imaging (MRI), PET scans, or ultrasounds may be used to determine whether and how ALL is affecting the organs, lungs, brain, or other areas of the body. 

Doctors tailor ALL treatment for each patient based on a number of factors, including the patient’s age and overall health, and the subtype of ALL involved.

The results of molecular and genetic testing will also considered. If present, the Philadelphia chromosome may mean that a targeted therapy, called tyrosine kinase inhibitor (TKI), will be a part of the treatment. TKIs targeting the Philadelphia chromosome include imatinib, dasatinib, nilotinib, bosutinib, and ponatinib.  

In nearly all cases, treatment of ALL is divided into three phases:

• Induction of remission. In this phase, the goal is put the cancer into complete remission by killing as many leukemia cells as possible. Complete remission means that conventional diagnostic tests are no longer able to detect leukemia cells and the patient does not have any symptoms. This phase typically involves the use of combinations of chemotherapy and other drugs, including corticosteroids and, in some cases, immunotherapy (drugs that boost or suppress the patient’s immune system to better fight the cancer). In Philadelphia chromosome positive ALL, the TKI is used in combination with chemotherapy and/or corticosteroids.
  
  During this phase of treatment, what’s called “prophylaxis of the central nervous system (CNS)” is used. In this process, patients are treated with injections of chemotherapy drugs into their cerebrospinal fluid (CSF), which bathes the spinal cord, to prevent leukemia cells from spreading to the tissue around the brain and spinal cord—or to destroy leukemia cells that have already spread to this area. In the latter case, radiation therapy may also be employed. 
  
• Consolidation therapy. Once remission is achieved, patients begin the next phase, which is intended to kill any remaining leukemia cells. Patients continue CNS prophylaxis. But depending on the subtype of ALL and specific treatment program for a particular patient, consolidation therapy may consist of high-dose chemotherapy treatments taken at regular intervals over the course of several weeks, as well as immunotherapy, and/or targeted therapy. 
  
  People with a subtype of ALL that has a high risk of returning may also be treated with a stem cell transplantation.
  
  
• Remission maintenance therapy. In the last phase of treatment, patients continue one or more drugs for, on average, two to three years.

After remission maintenance therapy, there is a chance that ALL will return, and sometimes, the leukemia cells do not respond well to medications, making remission difficult to achieve. In these cases, doctors may use different or higher-dose chemotherapy, monoclonal antibodies, CAR T-cell therapy, targeted therapy, or a stem cell transplantation to treat the cancer. Doctors may also offer patients the opportunity to join a clinical trial with a new treatment—or begin palliative treatment.

The outlook for people with ALL varies based on several factors, among them the age and overall health of the patient, as well as the subtype of ALL.

The prognosis for children, adolescents, and young adults with ALL is generally very good. Remission occurs in around 98% of cases in people aged 18 or under, and the five-year survival rate for this age group is over 90%.

Young adults, with good overall health, can have a favorable prognosis similar to pediatric patients when treated with regimens inspired by pediatric protocols. Outcomes for older adults are not as good as those of children and adolescents/young adults.

After completing initial treatment for ALL, people should continue to see their doctor regularly to monitor their health and a possible recurrence of the leukemia.

“At Yale, patients with ALL receive personalized care from a team that includes physicians, advanced practice providers, nurses, clinical trial personnel, social workers, and nutritionists who are experienced in the treatment of this rare leukemia,” says Dr. Mendez. “State-of-the-art technology is used to characterize the subtype of ALL at diagnosis and to monitor the response to treatment. We offer a range of treatments that are tailored to the individual and the subtype of ALL, ranging from chemotherapy and targeted therapy, to cellular therapies including allogeneic stem cell transplantation and CAR-T therapy. Novel therapies and treatment regimens for ALL that are under investigation are offered through clinical trials.”