What is Acute Lymphoblastic Leukemia?

Acute lymphoblastic leukemia (ALL) is a type of cancer that originates in the bone marrow, where it leads to the overproduction of immature lymphocytes, a type of white blood cell. This condition is more commonly diagnosed in children, but it also affects adults, where the prognosis tends to be less favorable^1,2,3.

The image is taken from IHH Healthcare Singapore

Causes and Risk Factors

The exact causes of ALL are not fully understood, but several risk factors have been identified. These include genetic factors, such as the presence of certain chromosomal abnormalities like the Philadelphia chromosome, and environmental exposures, such as radiation and certain chemicals like benzene^4,5. Previous chemotherapy or radiation therapy for other cancers also increases the risk ⁵.

Symptoms

The symptoms of acute lymphoblastic leukemia (ALL) in adults can vary but generally include a range of signs that may initially resemble those of the flu or other common, less serious conditions. Some symptoms result from the leukemia cells interfering with the development and maturation of normal blood cells in the bone marrow, leading to a shortage of normal blood cells. Other symptoms are related to the direct toxicity of cancer cells to various organs and tissues. 

The main symptoms include:

• Weakness or feeling tired, usually due to anemia because of low red blood cells^1,2,3
• Fever or night sweats, so-called “B” symptoms, common for blood cancers^1,2,3
• Easy bruising or bleeding, due to low platelets ^1,2,3
• Petechiae (flat, pinpoint spots under the skin caused by bleeding)¹
• Wheezing, coughing, painful breathing, and shortness of breath^1,3
• Weight loss or loss of appetite^2,3
• Pain in the bones or stomach¹
• Pain or feeling of fullness below the ribs, usually due to liver and/or spleen enlargement¹
• Swollen lymph nodes, which may be noticed as painless lumps in the neck, underarm, stomach, or groin^1,2
• Frequent infections, due to the low number of mature lymphocytes and other immune cells^1,2,3
• Pale skin, due to anemia (low red blood cell count)^2,3
• Dizziness or feeling lightheaded^2,3
• Frequent or severe nosebleeds, Bleeding gums^2,3

It’s important to note that these symptoms are not exclusive to ALL and can be caused by other conditions. Therefore, if someone experiences these symptoms, it’s crucial to consult a healthcare provider for a proper diagnosis and treatment plan.

Diagnosis and Types

The diagnosis of acute lymphoblastic leukemia (ALL) involves a series of tests that examine the blood and bone marrow to confirm the presence of leukemic cells and to identify the subtype of ALL. An accurate diagnosis of the subtype is crucial as it influences the treatment approach and prognosis².

Diagnostic tests for Acute lymphoblastic leukemia (ALL)

1. Blood Tests: A Complete Blood Count (CBC) with differential is often the first step in diagnosing ALL. These tests can reveal abnormal levels of white blood cells, red blood cells, and platelets, which may suggest leukemia^3,4.
2. Bone Marrow Tests: Bone marrow aspiration and biopsy are critical for confirming a diagnosis of ALL. These procedures involve removing a sample of bone marrow from the hip bone and examining it for the presence of leukemic blast cells. In ALL, at least 20% of the cells in the bone marrow are lymphoblasts⁵.
3. Immunophenotyping (Flow Cytometry): This test identifies the specific types of cells involved in ALL by examining the proteins on the surface of the cells. It helps determine whether the leukemia cells are B cells or T cells, which are subtypes of lymphocytes^3,4,5.
4. Genetic Tests: Cytogenetic and molecular tests look for specific genetic abnormalities that may affect prognosis and treatment. These tests are essential for disease evaluation, risk stratification, and treatment planning^3,5.

Types of ALL

ALL is classified into two main subtypes based on the type of lymphocyte affected:

1. B-cell ALL (B-lymphoblastic leukemia/lymphoma): This is the most common subtype of ALL, where the B-cell lymphocytes are affected. Among adults, B-cell lineage represents 75 percent of cases^3,6.
2. T-cell ALL (T-lymphoblastic leukemia): This subtype originates in immature cells that would normally develop into T-cell lymphocytes. It is less common and occurs more often in adults than in children. Among adults, T-cell lineage represents about 25 percent of cases^3,6.

In addition to classifying ALL as either B-cell or T-cell, it is further classified based on specific genetic abnormalities found in the leukemia cells. Identifying these abnormalities is critical for determining the prognosis and guiding treatment decisions³.

Treatment

The treatment of acute lymphoblastic leukemia (ALL) in adults involves a comprehensive approach that includes chemotherapy, targeted therapy, immunotherapy, and stem cell transplantation. Here’s a detailed overview of the treatment options based on the provided sources:

Chemotherapy

Chemotherapy is the cornerstone of ALL treatment and is typically administered in phases: induction, consolidation, and maintenance. The induction phase aims to achieve remission by killing the leukemia cells in the blood and bone marrow. The consolidation phase helps eliminate any remaining leukemia cells, and the maintenance phase prevents the leukemia from returning^2,7,8

Targeted Therapy

Targeted therapies are used to treat specific genetic abnormalities in leukemia cells. For example, tyrosine kinase inhibitors (TKIs) like imatinib, dasatinib, and nilotinib are used for Philadelphia chromosome-positive (Ph+) ALL. These drugs target the abnormal protein produced by the BCR-ABL gene fusion^9,10.

Immunotherapy

Immunotherapies such as blinatumomab and inotuzumab ozogamicin are used to target specific antigens on the surface of leukemia cells. Blinatumomab brings T cells close to cancer cells to enhance the immune response against cancer, while inotuzumab ozogamicin delivers a toxin directly to the cancer cells^9,11.

Stem Cell Transplantation

Stem cell transplantation may be considered for patients in remission, especially those with high-risk features. Allogeneic stem cell transplantation, where stem cells are received from a donor, is preferred because it can also create a graft-versus-leukemia effect, helping to eliminate any remaining leukemia cells. Autologous stem cell transplantation (using the patient’s own cells) is less common due to the risk of reintroducing leukemia cells ^12,13,.

Watch this short video from Pfizer UK about patients who underwent a stem cell transplant.

Central Nervous System (CNS) Prophylaxis

Since ALL can spread to the brain and spinal cord, CNS prophylaxis is an important part of the treatment. This may include intrathecal chemotherapy (direct injection into the spinal fluid) and, less commonly, cranial irradiation¹².

Palliative and Supportive Care

For patients who cannot tolerate aggressive treatment or in cases where treatment is unlikely to cure the leukemia, palliative and supportive care may be used to manage symptoms and improve quality of life. This can include less intensive chemotherapy, pain management, and treatments to manage other symptoms caused by leukemia or its treatment⁹. 

Watch this informative video about ALL treatment in adults by Marlise Luskin MD, MSCE from “Dana-Farber Cancer Institute”

Clinical Trials

The ongoing clinical trials for acute lymphoblastic leukemia (ALL) are diverse and target various aspects of the disease, from initial treatment strategies to interventions for relapsed or refractory cases. Here are some of the key ongoing trials:

1. UCSF Acute Lymphoblastic Leukemia Clinical Trials for 2024:
   • A Phase 1 study involving BMF-500, an oral FLT3 inhibitor, is currently recruiting adult patients with acute leukemia to determine the optimal dosages and expansion of the dose¹⁴.
   • Another study is evaluating the safety and tolerability of JNJ-75276617 in both dose escalation and dose expansion phases¹⁴.
   • The study on cancer care delivery in adolescent and young adult patients with ALL aims to improve adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines¹⁴.
2. Johns Hopkins Medicine Clinical Trials:
   • Various trials are testing new drugs and treatment methods, including a Phase Ib/II study of Venetoclax in combination with Liposomal Vincristine for relapsed or refractory T-cell or B-cell ALL¹⁵.
   • Another trial is investigating the use of steroids and tyrosine kinase inhibitors with Blinatumomab or chemotherapy for newly diagnosed BCR-ABL-positive ALL in adults¹⁵.
3. Mayo Clinic Research:
   • A phase 3 randomized, open-label study is designed to evaluate the efficacy of treatments for adult subjects with Relapsed/Refractory (R/R) B-precursor ALL¹⁶.
4. Leukemia & Lymphoma Society:
   • Emphasizes the importance of clinical trials as a treatment choice for some ALL patients, highlighting that trials are available for patients at every treatment stage and those in remission¹⁷.

These trials reflect a broad spectrum of research focusing on optimizing existing therapies and exploring new therapeutic strategies. They are crucial for advancing the treatment of ALL and potentially improving outcomes for patients at various stages of the disease.

Prognosis and Survival

The prognosis and survival rates for acute lymphoblastic leukemia (ALL) vary significantly based on age, genetic factors, and response to treatment. Here are the key points from the sources provided:

Survival Rates by Age Group

• Children: The prognosis for children with ALL is generally favorable, with a high chance of achieving remission and a cure. The 5-year survival rate for children is approximately 85% to 90%^18,19.
• Adults: Survival rates for adults are lower compared to children. The 5-year survival rate for adults varies:
  • For those younger than 15 to 39 years, the survival rate is about 65%²⁰.
  • For adults aged 40 and older, the survival rate drops to around 20%²⁰.
  • Overall, more than 65% of people with ALL will survive for 5 years or more after being diagnosed²⁰.

Factors Affecting Prognosis

• Age: Younger patients generally have a better prognosis^21,22.
• Genetic Abnormalities: Certain genetic changes can significantly affect prognosis. For example, the presence of the Philadelphia chromosome is a critical factor; however, treatments targeting this mutation have improved outcomes^21,22
• White Blood Cell Count at Diagnosis: A lower white blood cell count at diagnosis is associated with a better prognosis^22,23.
• Response to Treatment: Achieving complete remission, particularly within the first few weeks of treatment, is associated with a better prognosis^22,23.
• A subtype of ALL: The specific type of ALL (e.g., B-cell or T-cell) can influence the prognosis²³.

Improvements Over Time

• Advances in treatment, including the use of pediatric protocols in young adults and targeted therapies for specific genetic mutations, have improved survival rates over the past decades^24,25.
• The overall 5-year survival rate has increased from earlier decades, showing improvement in both disease management and outcomes^24,26.

Challenges and Considerations

• Despite high remission rates, relapse remains a significant challenge, particularly in adults, where survival rates after relapse are lower ²⁷.
• Prognostic factors are crucial for tailoring treatment approaches and managing expectations regarding outcomes^28,29.

In summary, while the prognosis for ALL has improved with advancements in treatment, significant disparities in outcomes based on age and genetic factors persist. Younger patients and those with favorable genetic profiles tend to have better outcomes, whereas older adults and those with high-risk genetic mutations face more challenges.

Watch this video from Pfizer UK about the survival stories of patients

Patient’s Survivorship

Acute Lymphoblastic Leukemia (ALL) in adults is a challenging condition that involves complex treatment regimens and potential complications both during and after treatment. Understanding these challenges and knowing how to manage them is crucial for patients and their healthcare teams.

During Treatment

Side Effects of Chemotherapy

Chemotherapy, the mainstay of ALL treatment, can cause a range of side effects due to its impact on both cancerous and healthy cells. Common side effects include:

• Low Blood Cell Counts: This can lead to an increased risk of infection (neutropenia), bleeding or bruising from minor injuries (thrombocytopenia), and fatigue (anemia)^27,30.
• Infection: Patients are at a higher risk due to compromised immune systems. It’s crucial to avoid exposure to contagious diseases and maintain strict hygiene practices³¹.
• Tumor Lysis Syndrome (TLS): Rapid destruction of leukemia cells releases their contents into the bloodstream, potentially leading to kidney failure and other serious conditions. Preventive measures include hydration and medications like allopurinol or rasburicase³⁰.
• Graft Versus Host Disease (GVHD): For those undergoing stem cell transplantation, GVHD is a risk where the donor’s immune cells attack the patient’s tissues, leading to various symptoms²⁷.

Management Strategies

• Regular Monitoring: Frequent follow-up exams and tests are essential to monitor for side effects and adjust treatment as necessary³⁰.
• Supportive Care: This includes medications to manage side effects, transfusions for low blood counts, and antibiotics for infections³¹.
• Patient Education: Patients should be educated on the importance of reporting new symptoms, practicing infection prevention measures, and adhering to a neutropenic diet when necessary³¹.

After Treatment

Long-term Effects and Relapse

• Secondary Cancers: Some treatments for ALL can increase the risk of developing another cancer later in life³⁰.
• Chronic Health Issues: Some patients may experience ongoing health problems related to their treatment, such as heart or lung issues, or fertility problems²⁷.
• Relapse: There’s always a risk that ALL can return. Symptoms of relapse are similar to those at initial diagnosis and should prompt immediate medical attention³².

Follow-up Care

• Regular Check-ups: Continued monitoring is crucial for early detection of relapse or secondary cancers. This typically involves physical exams, blood tests, and sometimes bone marrow biopsies³⁰.
• Survivorship Care Plan: Patients should have a plan that outlines follow-up care, potential long-term effects of treatment, and lifestyle recommendations³⁰.
• Mental Health Support: The psychological impact of cancer treatment can be significant. Access to mental health services and support groups is important for coping with anxiety about relapse and adjusting to life after cancer³⁰.

Recommendations for Patients

• Stay Informed: Understand your treatment, its side effects, and the signs of relapse.
• Adhere to Follow-up Care: Attend all scheduled appointments and perform recommended tests.
• Manage Side Effects: Communicate with your healthcare team about any side effects to find effective management strategies.
• Seek Support: Consider joining support groups or seeking counseling to address emotional and psychological challenges.
• Maintain a Healthy Lifestyle: Engage in physical activity, eat a balanced diet, and avoid tobacco and excessive alcohol to support overall health.

In summary, managing ALL in adults requires a comprehensive approach that addresses the immediate challenges of treatment and the long-term needs of survivors. Collaboration between patients, their families, and healthcare providers is key to navigating these complexities successfully.

Another informative video about ALL in adults that worts watching from “Leukemia and Lymphoma Society”

See also

Clinicaltrials.gov – a huge database of clinical trials, useful for patients and families to find past, ongoing, and upcoming clinical trials.

Cancer.Net – Comprehensive information for people with cancer, families, and caregivers, from the American Society of Clinical Oncology (ASCO)

Cancer.Gov – Comprehensive overview of the treatment of acute lymphoblastic leukemia by NCI

Leukemia and Lymphoma Society – national, voluntary health agency dedicated to curing leukemia, lymphoma, Hodgkin’s disease, and myeloma, and to improving the quality of life of patients and their families.

Oncodaily.com – Online platform where you can find anything related to cancers such as everyday news, blogs, videos, podcasts, etc.