General principles and stages of combination chemotherapy
The modern strategy for combating leukemias involves long-term and multi-stage treatment with regular rotation of chemotherapy drug combinations.
The entire protocol is structurally divided into several key phases:
- Remission induction. The most aggressive stage, the task of which is to destroy the main bulk of blasts. Combinations of three or more drugs in high doses are used.
- Consolidation. Administration of a series of combination chemotherapy courses to eliminate the residual pool of tumor cells. Drug dosages here are medium or low.
- Maintenance therapy. The longest stage, aimed at preventing disease relapse. The child receives low doses of cytostatics.
- Re-induction courses. Temporary intensification of treatment during the maintenance phase (addition of several active drugs).
- Prevention of neuroleukemia. A mandatory part of the protocol. Since systemic chemotherapy penetrates the blood-brain barrier extremely poorly, cytostatics are administered intrathecally (into the cerebrospinal fluid space). Patients in the intermediate and high-risk groups are additionally prescribed cranial irradiation.
Pharmacotherapy depending on the type of leukemia
Tactics and drug selection are strictly tied to the lineage affiliation of the tumor cells.
Acute lymphoblastic leukemia (ALL) The baseline regimen is based on a combination of glucocorticoids (dexamethasone, prednisolone), enzyme preparations (L-asparaginase), and a wide range of cytostatics, such as vincristine, methotrexate, cyclophosphamide, and cytarabine. Bone marrow transplantation (BMT) in ALL is usually considered only in the event of a relapse.
Acute myeloid leukemia (AML) Here, the basis of therapy consists of other cytostatics — cytarabine, daunorubicin, and etoposide. In myeloid forms, BMT is required much more frequently and is performed in the early stages of treatment. The prognosis for AML is significantly worse: overall 5-year survival is less than 50%.
A special place is occupied by the promyelocytic variant (AML M3). In addition to chemotherapy, a targeted drug is used for its treatment — trans-retinoic acid. It is unique in that it does not destroy tumor elements, but overcomes their maturation block, forcing blasts to differentiate into normal cells.
Complications of antineoplastic therapy
Aggressive impact on the body inevitably causes severe, and at times life-threatening, side effects. Allergic or autoimmune reactions (such as bronchial asthma) are uncharacteristic of such treatment. Other conditions are much more dangerous:
- Direct toxicity. Rapidly dividing and highly specialized tissues suffer: myelosuppression (bone marrow damage), toxic damage to the liver, kidneys, heart, nervous system, and lungs develop.
- Infections and sepsis. They occur against the background of deep immunodeficiency caused by drug-induced neutropenia, a decrease in T-lymphocyte levels, γ-globulin deficiency, and the destruction of the protective barriers of the skin and mucous membranes.
- Acute renal failure. Associated with tumor lysis syndrome. Renal tubules are simply blocked by the lysis products of blast cells.
- Thrombosis. The risk of blood clot formation increases sharply with the use of L-asparaginase, glucocorticoids, and the presence of permanent central venous catheters.
- Late consequences. In children, therapy can provoke growth retardation and the appearance of secondary (induced) tumors in the future.
Supportive care and monitoring
Combination chemotherapy is impossible without supportive care. It does not kill the leukemia, but corrects homeostasis and saves the patient from toxicity.
Supportive care includes:
- Replacement hemotherapy (transfusion of plasma, red blood cell and platelet concentrates) to compensate for blood cell deficiencies.
- Infection control. Antibiotics, antimycotics, antiviral drugs, and immunoglobulins are used. Recombinant granulocyte colony-stimulating factor (G-CSF) is used to stimulate the production of own neutrophils.
- Detoxification (infusions and metabolic agents) and correction of hemostasis (anticoagulants for the prevention of thrombosis).
There is no primary prevention of leukemias. Secondary prevention comes down to compliance with the maintenance therapy protocol. Patients are under the joint supervision of a pediatrician and an oncohematologist throughout their lives. Any vaccination is carried out strictly according to an individual schedule, taking into account the epidemiological situation.
To remember the main phases of systemic treatment, you can use the abbreviation ICP: Induction (maximum hit) — Consolidation (securing success) — Maintenance (long-term protection).
Class and exam questions
Why is it mandatory to administer drugs into the spinal canal in leukemias?
This is necessary for the prevention or treatment of neuroleukemia. Systemic cytostatics administered intravenously hardly cross the blood-brain barrier, leaving the central nervous system vulnerable to tumor cells.
How does trans-retinoic acid work in acute promyelocytic leukemia?
Unlike classical chemotherapy, it acts as a targeted drug. The acid does not cause cell death, but eliminates their maturation block, inducing normal blast differentiation.
Why do kidneys often fail during leukemia treatment?
The main reason is tumor lysis syndrome. Massive death of tumor cells under the action of chemotherapy leads to the release of a huge amount of intracellular products that physically block the renal tubules.
What else to study on this topic
- Pathogenesis of tumor lysis syndrome and methods for its prevention
- Mechanisms of action of L-asparaginase on the hemostatic system
- Indications and protocols for bone marrow transplantation in AML
- Protocols for the management of patients with febrile neutropenia
- Mechanisms of development of secondary tumors after combination chemotherapy
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Other topics in "Chapter 10. Diseases of the Blood and Blood-Forming Organs"
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