How is acute lymphoblastic leukemia treated?

The basic principles of treatment of acute lymphoblastic leukemia in children have been developed in the US back in the late 1960s. In fact, they have not changed to date. Modern treatment of acute lymphoblastic leukemia consists of several main phases: induction of remission with the use of three or more agents administered within 4-6 weeks, multi-agent consolidation ("fixing") of remission and maintenance therapy, usually using antimetabolites for 2- 3 years. A mandatory component is the prevention and treatment of neiroleukemia. Given the poor penetration of drugs through the blood-brain barrier, as early as 1965, it was proposed to use specific therapy aimed at sanation of the central nervous system. Children With a T-cell variant of acute lymphoblastic leukemia, high leukocytosis and children under the age of one year are classified as a high-risk group for the development of neuroleukemia. The main methods of prevention and treatment of neuroleukemia are the intrathecal administration of chemotherapy drugs (methotrexate, cytarabine, prednisolone) at age doses and cranial irradiation at an early stage from the start of treatment.

Theoretically, therapy should last until the entire population of leukemic cells is destroyed, but not longer. Unfortunately, until now there is no reliable method for determining the residual tumor, however, in randomized clinical trials it has been shown that the optimal duration of therapy is 2-3 years. Typically, the treatment consists of daily taking of mercaptopurine and weekly administration of methotrexate, the dose is modified depending on the number of leukocytes.

By the end of the 1970s, it became clear that such therapy could cure only half of children with acute lymphoblastic leukemia. Further progress is related to the determination of the biological heterogeneity of lymphoblastic leukemia, the introduction of the international cytological classification (FAB) and the 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 studies in the pharmacokinetics of various cytotoxic drugs with the aim of creating more effective regimens of chemotherapy) and intensive development will accompany tion therapy.

All this led to the creation of the next generation of chemotherapy programs for acute lymphoblastic leukemia. Most modern protocols are based on the principles of intensive initial polychemotherapy for maximum destruction of the leukemic cell pool. Their basis is the use of cytotoxic drugs in the form of successive combinations (rotation), the use of high-dose regimes of chemotherapy, as well as intensive prevention of neiroleukemia with the use of cranial irradiation in most cases. These achievements enabled the USA and Western European countries to overcome by the end of the 1980s the 70% barrier of 5-year recurrence-free survival in acute lymphoblastic leukemia. The best protocols currently in use include the programs of the BFM and COALL (Germany) groups, as well as a number of protocols of American research groups - DFCI 8.1-01. POG. CCSG.

Based on the results of treatment according to these protocols, as well as on the experience accumulated by the BFM group, a new program for treatment of acute lymphoblastic leukemia in children, named Moscow-Berlin 91 (ALL-MB-91), was developed. 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 lymphocytic leukemia in children. In this protocol, prednisolone has been replaced with dexamethasone, a long-lasting (for several months) application of asparaginase has been introduced. Local chemoprophylaxis of neiroleukemia is carried out during the first year of treatment with three drugs. The special requirements of the new protocol are the refusal to use high-dose intensive chemotherapy and treatment of patients on an outpatient basis, a reduction in the need for accompanying therapy and transfusions of blood components, and the rejection of cranial irradiation in most patients.

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

[1], [2], [3], [4], [5], [6], [7]