How are non-Hodgkin's lymphomas treated?

Of fundamental importance is adequate treatment of initial syndromes caused by the localization and mass of the tumor (compression syndromes) and metabolic disorders due to its disintegration (tumor lysis syndrome). In non-Hodgkin's lymphoma, therapeutic measures begin immediately upon admission of the patient to the hospital with ensuring venous access, deciding on the need and nature of infusion and antibacterial therapy. Initial treatment of non-Hodgkin's lymphoma is carried out through a peripheral catheter, catheterization of the central vein is performed under general anesthesia simultaneously with diagnostic procedures. Monitoring of biochemical parameters is mandatory for timely detection of metabolic disorders.

The basis of effective treatment of childhood non-Hodgkin's lymphomas is polychemotherapy. The regimens and intensity of which are determined by the variant and stage of the disease. For all childhood non-Hodgkin's lymphomas, prevention of neuroleukemia is mandatory. Local (to the site of the lesion) radiation therapy is not used, except in rare cases (to reduce the tumor mass in compression syndrome).

Different countries offer approximately the same effective treatment programs for non-Hodgkin's lymphomas in children. In Europe, these are the protocols of the BFM group (Germany, Austria) and SFOP (France). Programs based on the BFM group protocols of 1990 and 1995 are widely used, but, unfortunately, not always in a unified and correct manner.

Treatment programs for different types of non-Hodgkin's lymphomas vary. They depend on the histological structure and immunophenotype of the tumor. Lymphoblastic lymphomas from precursor cells (mainly T-, less often B-lineage) should be treated in the same way, regardless of the immunological affiliation. Another tactic is used for most childhood non-Hodgkin's lymphomas with a more mature B-cell immunophenotype - Burkitt's lymphoma and large B-cell lymphomas. A separate protocol is proposed within the framework of the BFM for anaplastic large cell and peripheral T-cell lymphoma. Thus, most children with non-Hodgkin's lymphomas (about 80%) receive therapy according to one of two basic protocols:

• for B-cell non-Hodgkin's lymphomas and for B-cell acute lymphoblastic leukemia;
• for non-B-cell lymphoblastic non-Hodgkin lymphomas.

Treatment of the last group of tumors is not an easy task, it is not yet successful enough. It is necessary to develop new programs using other groups of drugs, immunotherapy.

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Basic elements of programmatic polychemotherapy

Lymphoblastic lymphomas from precursor cells, predominantly T-cell, less commonly non-Hodgkin's lymphomas from B-cell lineage:

• a long-term continuous course of polychemotherapy, similar to programs for the treatment of acute lymphoblastic leukemia using glucocorticosteroids, vincristine, cyclophosphamide, methotrexate, etc. (total duration 24-30 months);
• basic drugs - anthracycline derivatives:
• continuous maintenance therapy with mercaptopurine and methotrexate for 1.5-2 years;
• the intensity of the initial phase of therapy is determined by the stage of the disease;
• Prevention and treatment of CNS damage include mandatory endolumbar administration of cytostatics (cytarabine and methotrexate) and glucocorticosteroids in age-appropriate doses, as well as cranial irradiation at a dose of 12-24 Gy for patients with stage III-IV lymphoma.

B-cell non-Hodgkin's lymphomas (Burkitt's and Burkitt-like lymphoma, diffuse large B-cell lymphomas):

• 5-6-day courses of high-dose polychemotherapy in a strictly defined regimen;
• the main drugs are high-dose methotrexate and cyclophosphamide (fractionation);
• the cytostatic load (number of courses) is determined by the stage of the disease, the mass of the tumor (calculated based on LDH activity), and the possibility of its complete resection;
• supportive therapy is not used;
• total duration of treatment - 2-6 courses from 1 to 6 months;
• prevention of CNS damage by endolumbar administration of cytostatics.

In the treatment of CNS lesions, the use of the Omayo reservoir is indicated. For high-risk patients (stage IV and B-cell acute lymphoblastic leukemia), in the absence of complete remission within the timeframes specified by the protocol, it is necessary to decide on the possibility of allogeneic or autogenous hematopoietic stem cell transplantation, the use of targeted immunotherapy and other experimental approaches.

The drug rituximab (mabthera), which appeared in recent years and contains humanized anti-CD20 antibodies, has shown good results in the treatment of aggressive B-cell lymphomas in adults. The drug made it possible to overcome the refractoriness of the tumor without having a pronounced toxic effect on the patient. Studies are being conducted with the inclusion of rituximab in polychemotherapy programs for children with B-cell acute lymphoblastic leukemia, with refractory course and relapses of B-cell non-Hodgkin's lymphomas.

The treatment protocol for anaplastic large cell lymphoma practically repeats the above-mentioned elements of a course of polychemotherapy without subsequent support. The intensity of polychemotherapy is lower than in the protocol for B-cell non-Hodgkin's lymphoma, mainly due to a lower dose of methotrexate (with the exception of stage IV of the disease, which is rarely observed in this type of lymphoma).

The cure rate (5-year event-free survival) in children with the main types of non-Hodgkin's lymphoma is, depending on the stage of the disease, about 80%: with localized tumors of stages I and II, the survival rate is almost 100%, in "advanced" stages (III and IV), especially with CNS damage, this figure is lower - 60-70%. That is why it is extremely important to detect the disease in a timely manner and begin treatment at the early stages of the disease, use the most radical therapy, and also look for new ways to influence the tumor.

Treatment of relapsed non-Hodgkin's lymphoma

Treatment of relapses of non-Hodgkin's lymphoma is a difficult task, and in Burkitt's lymphoma it is practically hopeless. In other types of lymphoma, the effectiveness of treatment in case of relapse is also very low. In addition to intensive polychemotherapy, experimental methods can be used in the treatment of relapses - immunotherapy with antibodies against tumor B-cells (rituximab) and hematopoietic stem cell transplantation.

Treatment protocols for childhood lymphomas include detailed development of diagnostic and therapeutic measures taking into account the characteristics of the course of the disease, possible urgent situations, as well as recommendations for assessing the effectiveness of the treatment and dynamic monitoring of patients after its completion. Implementation of program therapy is possible with strict adherence not only to polychemotherapy regimens, but also to the entire complex of the above measures in specialized departments as part of multidisciplinary highly qualified children's hospitals. Only this approach allows us to obtain good treatment results for non-Hodgkin's lymphoma - a highly malignant and one of the most common oncological diseases of childhood.