How is acute lymphoblastic leukemia treated?

The basic principles of treating acute lymphoblastic leukemia in children were developed in the United States in the late 1960s. In fact, they have not changed to this day. Modern treatment of acute lymphoblastic leukemia consists of several main phases: induction of remission using three or more agents administered over 4-6 weeks, multi-agent consolidation (“consolidation”) of remission, and maintenance therapy, usually using antimetabolites for 2-3 years. A mandatory component is the prevention and treatment of neuroleukemia. Given the poor penetration of drugs through the blood-brain barrier, back in 1965 it was proposed to use specific therapy aimed at sanitizing the central nervous system. Children with the T-cell variant of acute lymphoblastic leukemia, high leukocytosis, and children under one year of age are considered to be at high risk for developing neuroleukemia. The main methods of prevention and treatment of neuroleukemia are intrathecal administration of chemotherapy drugs (methotrexate, cytarabine, prednisolone) in age-appropriate doses and cranial irradiation early in the course of treatment.

Theoretically, therapy should last until the entire leukemia cell population is destroyed, but no longer. Unfortunately, there is no reliable method to determine residual tumor, but randomized clinical trials have shown that the optimal duration of therapy is 2-3 years. Treatment typically consists of daily mercaptopurine and weekly methotrexate, with doses adjusted depending on the white blood cell count.

By the end of the 1970s, it became clear that such therapy could cure only half of children with acute lymphoblastic leukemia. Further progress was associated with the definition of the biological heterogeneity of lymphoblastic leukemia, the introduction of the international cytological classification (FAB) and a system of prognostic factors, the division of patients into risk groups and the development of differentiated treatment programs, the organization of multicenter studies and cooperative clinical groups, the development of research in the field of pharmacokinetics of various cytostatic drugs (with the aim of creating more effective chemotherapy regimens) and the intensive development of accompanying therapy.

All this led to the creation of the next generation of chemotherapy programs for acute lymphoblastic leukemia. Most modern protocols are built on the principles of intensive initial polychemotherapy for maximum destruction of the leukemic cell pool. They are based on the use of cytostatic drugs in the form of alternating combinations (rotation), the use of high-dose chemotherapy regimens, as well as intensive prevention of neuroleukemia using cranial irradiation in most cases. These achievements made it possible to overcome the 70% barrier of 5-year relapse-free survival in acute lymphoblastic leukemia in the USA and Western Europe by the end of the 1980s. The best protocols currently used include the programs of the BFM and COALL groups (Germany), as well as a number of protocols of American research groups - DFCI 8.1-01. POG. CCSG.

Based on the treatment results according to these protocols, as well as on the experience accumulated by the BFM group, a new program for the treatment of acute lymphoblastic leukemia in children was developed, called Moscow-Berlin 91 (ALL-MB-91). The main idea of this chemotherapy program is the idea of the key role of occult (latent) neuroleukemia in the origin of relapses and, consequently, failures in the treatment of acute lymphoblastic leukemia in children. In this protocol, prednisolone is replaced by dexamethasone, a regimen of long-term (for several months) use of asparaginase is introduced. Local chemoprophylaxis of neuroleukemia is carried out during the first year of treatment with three drugs. Special requirements of the new protocol are the refusal to use high-dose intensive chemotherapy and treatment of patients on an outpatient basis, a decrease in the need for accompanying therapy and transfusions of blood components, as well as the refusal of cranial irradiation in most patients.

The treatment results were completely comparable with the ALL-BFM-90 program.

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