Acute lymphoblastic leukemia (ALL)

Content:

Acute lymphoblastic leukemia (ALL) is a malignant lesion of the hematopoietic system, accompanied by an uncontrolled increase in the number of lymphoblasts.

The pathology is one of the most common types of cancer in children. This disease is characterized by uncontrolled growth of immature lymphocytes (lymphoblasts) in the bone marrow, which leads to disruption of normal hematopoiesis.

Statistics on the incidence of ALL in children in Belarus and the world are as follows:

In Belarus:

  1. accounts for 25–30% of all malignant tumors in children and up to 90% of cases of acute leukemia;
  2. the incidence rate of ALL in the Republic of Belarus is 4.2 per 100,000 children per year;
  3. the peak occurs between the ages of 2 and 5 years;
  4. Boys get sick more often than girls (the ratio is approximately 1.2:1).

In the world:

  1. About 100,000 new cases of ALL are registered annually in children under 15 years of age;
  2. ALL is the most common type of cancer, accounting for about 25-30% of all cases.
  3. The incidence of the disease is higher in developed countries compared to developing countries.

The word “acute” in acute lymphocytic leukemia comes from the fact that the disease progresses rapidly and results in the formation of immature blood cells.

Thanks to advances in medicine and better treatments, survival rates for childhood acute lymphoblastic leukemia have improved significantly in recent decades.

In developed countries, overall 5-year survival rates for childhood ALL reach 80-90%. However, in developing countries, these rates remain lower due to limited access to modern treatments and early diagnosis.

Symptoms of the disease

The disease manifests itself through various symptoms, which often have a non-specific coloring and resemble the signs of other diseases. These include:

  1. Frequent infections and fever. Due to the disruption of normal hematopoiesis and a decrease in the number of healthy immune cells, children with ALL are more susceptible to infections that are accompanied by elevated body temperature;
  2. increased fatigue and weakness. Decreased red blood cell count (anemia)
  3. leads to chronic fatigue, weakness, pale skin;
  4. bruising and hematomas. Insufficient platelet levels – thrombocytopenia (cells involved in blood clotting) causes frequent bruising, nosebleeds or bleeding gums;
  5. pain in bones and joints. Infiltration by leukemic cells leads to pain in bones, joints and muscles;
  6. loss of appetite, sudden weight loss. Due to general malaise and the effects of leukemia cells on the body, ALL patients experience loss of appetite and, as a result, weight loss;
  7. enlarged lymph nodes;
  8. headaches and visual disturbances.

Diagnostics

Pathology diagnostics includes a range of different methods aimed at identifying and characterizing tumor cells, as well as assessing the prevalence of the disease. The key methods are:

  1. General blood test: Helps to identify abnormalities in the number of leukocytes, erythrocytes and platelets, which serves as a basis for further examination;
  2. myelogram (bone marrow puncture). This is an invasive procedure in which a sample of bone marrow is taken for cytological and immunophenotypic analysis. It allows identifying the type of leukemic cells and their number in the bone marrow;
  3. immunophenotyping. A method based on the detection of specific antigens on the surface of tumor cells using monoclonal antibodies. Allows for accurate classification of the type of leukemia and determination of its subtype;
  4. Cytogenetic studies. Include karyotyping and fluorescent in situ hybridization (FISH). These methods reveal chromosomal abnormalities and genetic disorders in leukemic cells, which has prognostic value and helps to choose the optimal therapy;
  5. Molecular genetic testing: Methods such as polymerase chain reaction (PCR) and sequencing can detect specific genetic mutations;
  6. Imaging methods. CT and MRI are used to assess the spread of the tumor process;
  7. lumbar puncture A procedure in which a sample of spinal fluid is taken to look for leukemia cells in the central nervous system.

An integrated approach that includes all of these methods allows not only to accurately diagnose ALL, but also to determine its subtype, stage and prognostic factors, which is critical for choosing the optimal therapeutic strategy and increasing the chances of successful treatment.

When confirming the diagnosis, before drawing up a treatment plan, the doctor needs to know whether the pathological cells have managed to settle in other organs. To obtain more accurate information, such methods as ultrasound, MRI, and skeletal bone scintigraphy will help.

To make sure whether the pathology has spread to the central nervous system, a lumbar puncture is necessary. After receiving it, the doctor examines it for leukemic cells. In addition, before complex therapy, the patient is checked for pathological conditions of the cardiovascular system (ECG, EchoCG).

Also, the studies are supplemented by laboratory diagnostics, allowing to assess the general condition of the body. It is assessed how leukemia affects the functioning of the kidneys, liver, and metabolism. Understanding the full picture makes it possible to identify the changes that may occur during therapy.

Treatment of pathology

Pediatric patients diagnosed with ALL are successfully treated at the Republican Scientific and Practical Center for Pediatric Oncology, Hematology and Immunology, which specializes in the treatment of childhood cancer.

The center employs top-level doctors, as well as specially trained medical personnel who understand the specifics of treatment and diagnosis of various forms of oncology in this age group.

The therapy is carried out in accordance with modern programs and protocols, the latest methods, drugs, and equipment are used. Doctors are in constant close contact, make adjustments to the plan, assess the risks and effectiveness of treatment.

Treatment methods

  1. Chemotherapy.The main method of treating acute lymphoblastic leukemia (ALL). It is aimed at destroying tumor cells and achieving remission. ALL therapy is usually carried out in several stages:
  • induction therapy. The goal of this stage is to achieve remission by rapidly destroying most of the leukemic cells. A combination of several cytostatic drugs is usually used, such as vincristine, daunorubicin, corticosteroids and L-asparaginase. This stage can last from 4 to 6 weeks;
  • consolidation therapy. After remission has occurred, further treatment is given to destroy any remaining leukemia cells. Higher doses of chemotherapy drugs are used, often in combination with high-dose methotrexate and cytarabine. This stage can take 2 to 3 months;
  • maintenance therapy. To prevent relapse and destroy residual leukemia cells, maintenance therapy is carried out using low doses of chemotherapy drugs. This stage can last from 2 to 3 years;
  • Prevention of central nervous system involvement. Since ALL can spread to the central nervous system, preventive treatment is performed using intrathecal chemotherapy;

Depending on the ALL subtype, risk, and response to treatment, chemotherapy regimens may vary. In addition, targeted therapy, which targets specific molecular targets in tumor cells, may be used in some cases.

ALL chemotherapy is often accompanied by serious side effects such as myelosuppression, infections, nausea, vomiting, etc. Therefore, patients need careful monitoring and supportive care to minimize these effects.

  1. Targeted therapyis a new promising direction in the treatment of acute lymphoblastic leukemia (ALL). Unlike traditional chemotherapy, which indiscriminately affects all rapidly dividing cells, targeted drugs are aimed at specific molecular targets present in tumor cells.

One of the most successful examples of targeted therapy in ALL is the use of tyrosine kinase inhibitors, such as imatinib and dasatinib. These drugs block the activity of the BCR-ABL protein, which is a key oncogene in Philadelphia chromosome-positive ALL (Ph+ ALL). Their inclusion in treatment regimens has significantly improved the prognosis for patients.

Another promising direction is the use of bispecific antibodies that simultaneously bind to tumor and immune cells, activating an antitumor response.

In addition, research is underway to develop targeted drugs that target other molecular targets, such as mutant forms of the FLT3, JAK, and NOTCH1 proteins, which are common in ALL.

  1. Hematopoietic stem cell (HSC) therapy.This approach involves transplanting healthy HSCs into a patient after high-dose chemotherapy or radiation therapy.

The HSC transplant procedure begins with the mobilization and collection of the patient’s own stem cells or those from a compatible donor. This is followed by intensive chemotherapy or whole-body radiation to destroy the tumor cells. This also damages healthy blood-forming cells, necessitating a subsequent HSC transplant.

After transplantation, the HSCs migrate to the recipient’s bone marrow and begin the process of restoring normal hematopoiesis. This process takes several weeks, during which the patient is under strict observation and receives supportive therapy to prevent infections and other complications.

Transplantation of HSCs from a compatible donor (allogeneic transplantation) has the added benefit of what is known as the “transplantation anti-leukemia effect.” This means that the transplanted donor immune cells can recognize and attack the recipient’s remaining tumor cells, reducing the risk of disease recurrence.

  1. Radiation therapy.Plays an important role in the complex treatment of ALL, especially in the presence of extramedullary lesions or when it is necessary to prevent damage to the central nervous system.

Traditionally, radiation therapy is used to irradiate the entire brain (cranial irradiation) to prevent or treat CNS damage. This is because ALL tumor cells can penetrate the blood-brain barrier and cause metastases to the CNS. Cranial irradiation is usually administered at a dose of 18-24 Gy, divided into several fractions [2].

However, in recent years there has been a trend towards dose reduction or complete abandonment of cranial irradiation in children with ALL due to the risk of developing neurological complications and secondary brain tumors. Instead, intrathecal administration of chemotherapeutic drugs (methotrexate, cytarabine) is increasingly used to prevent CNS damage.

Bibliography:

  1. Clinical guidelines for the diagnosis and treatment of acute leukemia in children / Edited by A.G. Rumyantsev, M.A. Maschan. – M.: N.N. Blokhin Russian Cancer Research Center, 2014. – 200 p.
  2. Diagnostics and therapy of acute leukemia in adults / Ed. V.G. Savchenko. – M.: Practical Medicine, 2013. – 400 p.
  3. Acute leukemia in children / Ed. by M.D. Alieva. – M.: Medicine, 2015. – 384 p.
  4. Terwilliger T., Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577. doi:10.1038/bcj.2017.53
  5. Hunger SP, Mullighan CG Acute lymphoblastic leukemia in children. N Engl J Med. 2015;373(16):1541-1552. doi:10.1056/NEJMra1400972