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Acute Lymphoblastic Leukemia (ALL) – Sheba Medical Center

Acute Lymphoblastic Leukemia (ALL)

Acute lymphoblastic leukemia occurs when a mutation changes bone marrow cells and causes them to continue growing and dividing unchecked. They typically develop at a certain rate and die off at certain intervals. The bone marrow creates immature cells known as myeloblasts, which mature into white blood cells. Leukemia is the result of this blood cell production becoming excessive and generating abnormal cells. These aberrant cells can accumulate and drive out healthy cells since they cannot function normally.

ALL is a fast-growing, aggressive kind of blood and bone marrow cancer that can strike anyone at any age, though it tends to affect kids more frequently. Every year, roughly 1,000 new cases of adult ALL are identified in the US.

Unlike many other cancers, acute lymphoblastic leukemia does not generally form tumors. Generally, it affects the body’s entire bone marrow and by the time it is discovered, it has spread to other organs. Therefore, ALL cannot be staged in the same manner as other cancers. Instead, ALL is classified primarily by the types of lymphocytes that are affected.

The type of ALL will dictate the approach doctors take to treat the malignancy.
Acute lymphoblastic leukemia can be classified into two main subtypes based on what subset of lymphocytes (white blood cells) it attacks.

B-cell ALL, accounting for about 85% of all cases, affects B lymphocytes that develop in the bone marrow. B lymphocytes have a major role in antibody creation and fighting off illnesses.

T-cell ALL attacks T lymphocytes. Unlike B lymphocytes, which mature in the bone marrow, T lymphocytes mature in the thymus (part of the lymphatic system). This is the less common type of ALL, accounting for about 15% of cases.

ALL causes and risk factors

While the exact cause of acute lymphoblastic leukemia remains unknown for the vast majority of cases, it is believed to result from a combination of genetic and environmental factors. Some genetic syndromes have been associated with an increased risk of developing ALL. Genetic syndromes and their potential role in increasing the risk of ALL:

| Ataxia Telangiectasia (AT):

Ataxia telangiectasia is a rare genetic disorder that affects multiple systems in the body. It is caused by mutations in the ATM gene, which plays a critical role in repairing damaged DNA. Individuals with AT have an increased sensitivity to ionizing radiation, leading to an increased risk of developing various cancers, including ALL.

| Bloom Syndrome:

Bloom syndrome is an autosomal recessive disorder caused by mutations in the BLM gene, involved in DNA repair. Individuals with Bloom syndrome have a higher susceptibility to DNA damage and chromosomal rearrangements, which can contribute to the development of ALL and other cancers.

| Down Syndrome (Trisomy 21):

Down syndrome is a chromosomal disorder caused by the presence of an extra copy of chromosome 21. Children with Down syndrome have a significantly increased risk of developing ALL compared to the general population. The exact reason for this higher risk is not entirely understood, but it may be related to altered immune function and genetic factors associated with chromosome 21.

| Fanconi Anemia:

Fanconi anemia is a rare inherited disorder that affects the body's ability to repair damaged DNA. Mutations in various genes involved in the Fanconi anemia pathway lead to an increased risk of developing leukemia, including ALL.

| Klinefelter Syndrome:

Klinefelter syndrome is a chromosomal disorder in males, characterized by the presence of an extra X chromosome (XXY). While not a common risk factor, some studies have suggested a slightly increased risk of leukemia, including ALL, in individuals with Klinefelter syndrome.

| Li-Fraumeni Syndrome:

Li-Fraumeni syndrome is a rare genetic disorder caused by mutations in the TP53 tumor suppressor gene, which plays a crucial role in preventing the growth of cancer cells. People with Li-Fraumeni syndrome have an exceptionally high risk of developing various types of cancer, including ALL.

| Neurofibromatosis Type 1 (NF1):

Neurofibromatosis type 1, also known as von Recklinghausen disease, is caused by mutations in the NF1 gene. While it is mainly associated with the development of benign tumors (neurofibromas), individuals with NF1 have a slightly increased risk of developing leukemia, including ALL.

| Wiskott-Aldrich Syndrome:

Wiskott-Aldrich syndrome is an X-linked recessive immunodeficiency disorder caused by mutations in the WAS gene. While it primarily affects the immune system, individuals with this syndrome have a higher risk of developing certain types of cancers, including leukemia.

It is important to note that having one of these genetic syndromes does not guarantee the development of ALL or any other cancer. The presence of these risk factors merely increases the likelihood of developing the disease.

Although research has shown that most cases of ALL are not hereditary, a family history of ALL may be a risk factor. Additionally, other factors, such as previous exposure to radiation therapy, chemotherapy and certain chemicals, and having particular viral infections, such as human T-cell lymphoma/leukemia virus-1 (HTLV-1), which is rare outside of the Caribbean and Japan,
may also contribute to the development of ALL.

ALL symptoms

The symptoms of ALL can vary depending on the stage of the disease and individual factors, but some common symptoms include:

Fatigue and weakness: Due to the reduced number of healthy blood cells, individuals with ALL may experience persistent fatigue and weakness.

Easy bruising and bleeding: Low platelet counts can lead to easy bruising, bleeding gums, nosebleeds and prolonged bleeding from small cuts.

Frequent and long-lasting infections: The lack of normal white blood cells can weaken the immune system, making individuals more susceptible to infections that may be more severe or prolonged.

Bone and joint pain: Leukemia cells may accumulate in and around the bones, leading to pain and discomfort, especially in the arms and legs.

Enlarged lymph nodes, liver and spleen: Swollen lymph nodes in the neck, armpits and groin, as well as an enlarged liver and spleen, are possible signs of ALL.

Loss of appetite and weight loss: Cancer cells can affect the body’s metabolism and lead to a reduced appetite and unintended weight loss.

Fever: Frequent or prolonged fevers may be an indication of an underlying infection or the body’s response to leukemia.

Night sweats: Excessive sweating during the night, unrelated to room temperature, can be a symptom of ALL.

Shortness of breath: ALL may lead to anemia, causing a decreased number of red blood cells, resulting in shortness of breath and dizziness.

ALL Diagnosis

A precise diagnosis of the exact ALL type is crucial for effective treatment. Sheba Medical Cancer Center is proud to have many high tech diagnostic techniques available, along with expert staff, for accurate diagnoses. Some of these techniques include bone marrow biopsies, FISH and quantitative PCR.

Presently, there are no special screening tests that can detect ALL at a very early stage. Our Hemato-Oncology Division employs a variety of specialized tests to obtain a precise, prompt and reliable diagnosis of acute lymphoblastic leukemia in Israel and the exact subtype of the cancer. Since this disease is relatively rare in adults, it is critical to undergo testing by an experienced team of medical experts, like the highly qualified physicians at Sheba Medical Center.

Blood Tests
Blood tests are generally the first step in diagnosing leukemia. These include taking a CBC (complete blood count) and a blood smear. Changes in the amount and appearance of different blood cells can help diagnose leukemia. Typically, patients with ALL have an abundance of lymphoblasts (immature white cells), and an insufficient amount of red blood cells or platelets.

Bone Marrow Biopsy
If the blood test results are suspicious, a bone marrow biopsy and aspiration is then done to assess the bone marrow. This test can diagnose ALL with a high level of accuracy. Cytogenetic and molecular analyses are performed from the aspiration.

Laboratory Tests
These tests can include complete blood counts (CBC), which assess the levels of various blood cells; bone marrow biopsies, to examine the presence of leukemia cells; and immunophenotyping, which helps classify the type of leukemia based on the characteristics of the cancerous cells. Additional tests such as cytogenetic analysis and molecular genetic tests are also crucial for identifying specific genetic abnormalities associated with ALL, providing valuable information for treatment planning and prognosis.

Spinal Tap or Lumbar Puncture:
A spinal tap or lumbar puncture is a critical procedure in the evaluation of ALL, performed to detect leukemia cells in the cerebrospinal fluid (CSF). This test helps determine if ALL has spread to the central nervous system (CNS), which is essential for customizing the treatment plan.

MRI or CT Scan:
An MRI (magnetic resonance imaging) or CT (computed tomography) scan can be utilized in ALL cases to assess if the leukemia has spread to the brain or other parts of the body. These imaging techniques provide detailed internal images, helping in the accurate staging of the disease and monitoring of its progression or response to treatment.

Chest X-ray
A chest X-ray is often used in the evaluation of ALL to check for signs of infection or to detect the presence of a mediastinal mass, which can occur in some types of leukemia. This imaging test provides crucial insights into the health of the lungs and the thoracic cavity, which can be affected by the spread of leukemia or by complications of treatment.

ALL Prognosis

Prognosis in ALL can be influenced by various factors. Here are some of the key factors that can affect the prognosis in ALL:

Age at Diagnosis: Children and young adults tend to have a better prognosis compared to older adults.

Subtype of ALL: Different subtypes of ALL may have different prognosis based on their genetic and molecular characteristics.

White Blood Cell Count at Diagnosis: A higher white blood cell count at the time of diagnosis may indicate a more aggressive form of ALL and can impact prognosis.

Cytogenetic Abnormalities: Certain genetic abnormalities in leukemic cells can affect treatment response and overall prognosis.

Minimal Residual Disease (MRD): MRD refers to the presence of a small number of leukemic cells that remain in the body after initial treatment. A lower MRD is associated with a better prognosis.

Response to Initial Treatment: How well the leukemia responds to initial induction therapy is a significant predictor of prognosis.

Presence of Chromosomal Abnormalities: Specific chromosomal abnormalities, such as the Philadelphia chromosome, can impact prognosis and treatment decisions.

Overall Health and Performance Status: The general health and functional status of the patient can influence the ability to tolerate aggressive treatments and affect prognosis.

Time of Relapse: An early relapse after initial treatment is generally associated with a poorer prognosis.

Central Nervous System (CNS) Involvement: The spread of leukemia to the central nervous system may mean a poorer prognosis and require additional treatments.

Sex: In some studies, females have been shown to have slightly better outcomes compared to males.

Drug Resistance: The development of resistance to certain chemotherapy drugs can complicate treatment and affect prognosis.

Bone Marrow Transplantation: Patients who undergo bone marrow transplantation may have different prognoses depending on factors such as donor type and the timing of the transplant.

Treatment Protocol and Intensity: The specific treatment protocol and its intensity can impact the response to therapy and overall prognosis.

Presence of Comorbidities: The presence of other health conditions in addition to ALL can affect treatment choices and influence prognosis.

Infection Control: The risk of infection during treatment can impact treatment outcomes, especially in patients with weakened immune systems.

It’s important to note that each patient’s case is unique, and prognosis is determined by taking into account multiple factors. Advances in medical research and individualized treatment approaches continue to improve the prognosis for many patients with ALL.

ALL Treatment at Sheba Medical Center

The usual treatment for acute lymphoblastic leukemia (ALL) involves a combination of several therapeutic modalities. The treatment approach may vary based on the patient’s age, overall health, subtype of ALL and other individual factors.

The primary treatment for ALL is typically chemotherapy. At Sheba Medical Cancer Center, we use the latest approved chemotherapy drugs, administered under strict safety guidelines.
The main goal of chemotherapy in ALL is to eradicate cancer cells and induce remission, allowing patients to regain their health and improve their chances of long-term survival.

During chemotherapy for ALL, patients receive a combination of powerful drugs designed to target and destroy leukemia cells. These drugs work by interfering with the cells’ ability to grow and divide rapidly, a hallmark of cancer. While chemotherapy also affects healthy cells that divide quickly, such as those in the bone marrow and digestive tract, the doses are carefully managed to minimize side effects and maintain the patient’s overall wellbeing.

The treatment process typically consists of several phases, starting with induction therapy. In this intensive phase, high doses of chemotherapy are administered to rapidly reduce the number of leukemia cells in the bone marrow and blood. Following induction, consolidation therapy aims to eliminate any residual leukemia cells that may not be immediately detectable.

Throughout the treatment journey, patients may experience a range of side effects, including fatigue, nausea, hair loss and increased susceptibility to infections. However, advancements in supportive care and medical management have significantly improved the quality of life for patients undergoing chemotherapy.

For ALL cases that can be brought into remission, bone marrow treatments may also be used. This procedure involves replacing the diseased bone marrow with healthy stem cells from a compatible donor. The stem cells used are donated from family members or unrelated individuals. The cells are harvested from peripheral blood, cord blood or bone marrow.

Chemotherapy or radiation are used to remove damaged bone marrow before intravenously administering healthy donor stem cells to the patient. The fresh stem cells move to the bone marrow, where they start to produce fresh blood cells. The stem cells used are donated from family members or unrelated individuals. The cells are harvested from peripheral blood, cord blood or bone marrow.

The Department of Bone Marrow Transplantation at Sheba Medical Center, the biggest hospital in Israel, has 14 private rooms as well as extensive, high-tech laboratories and clinics, allowing all steps of the transplant process to be successfully completed on-site. A broad group of internationally renowned specialists, including hematologists, medical oncologists and radiation oncologists, are employed by the department, which has carried out more than 2,000 transplants to date. They collaborate to give patients with the best possible care.

There are also other treatment options for acute lymphoblastic leukemia available at Sheba, including radiation therapy, which may be used in conjunction with chemotherapy.

Immunotherapy for ALL is another possibility, and we are still researching this treatment approach.

At the forefront of the field is CAR T-cell therapy for acute lymphoblastic leukemia. This groundbreaking treatment is offered at only a few places worldwide, one of which is Sheba Medical Center in Israel.

By harnessing the body’s own T cells, CAR T-cell therapy is a cutting-edge blood cancer treatment. The treatment involves taking blood samples from the patient, isolating T cells, and genetically modifying them to create CARs, or chimeric antigen receptors. These enable the T-cells to identify tumor cells, which they then target and kill. T-cells are modified, multiplied in a lab and then returned to the patient’s body.

Unfortunately, CAR T-cell therapy is only offered in a select few healthcare institutions worldwide and is frequently very costly as a revolutionary advanced treatment. The entire procedure, from lymphocyte collection to patient delivery, only takes about 10 days at Sheba Medical Center because the CAR T-cells are produced in-house in a specialized lab. Other hospitals, on the other hand, frequently use commercial CARs, which must be developed elsewhere before being imported to the United States and take months to become available. The patient’s condition can advance more quickly as a result of this delay, which may also lessen the body’s ability to respond to the CARs. Additionally, the procedure of transportation reduces the quality of the cells because some cells perish during the required freezing and thawing.

To learn more about CAR T-cell therapy for ALL, visit the link: https://www.shebaonline.org/who-can-benefit-from-acute-lymphoblastic-leukemia-car-t-therapy-in-israel/

At Sheba’s Hemato-Oncology Division, specially trained and well-known cancer specialists work together to assess each case of ALL and develop the most efficient treatment plan.

Whatever treatment options are used, our patients always receive complete care from a multidisciplinary team of oncologists, hematologists, radiation oncologists, nursing, and support staff. Our teams are in constant communication and collaboration with their clinician and research colleagues in order to present our patients with the best possible treatments.


Our doctors join together across a range of specialties to design your tailored and fully coordinated care – from your initial diagnosis through long-term care and monitoring. You will benefit from the expertise of our world-class physicians and highly trained nurses, social workers, nutritionists and other providers of holistic, integrative medicine. Medical treatments and technologies are constantly progressing, which is why it is vital to choose skilled, experienced doctors who keep pace with the latest research. Altogether, your Sheba team will treat your cancer with frontline therapies, while caring compassionately for you as a unique individual.

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