How are non-Hodgkin's lymphomas treated?

It is important to adequately treat the initial syndromes caused by the localization and mass of the tumor (contraction syndromes) and metabolic disorders due to its disintegration (tumor lysis syndrome). With non-Hodgkin's lymphoma, therapeutic measures begin immediately when the patient enters the hospital with the provision of venous access, resolving the need for and the nature of infusion and antibiotic therapy. Initial treatment of non-Hodgkin's lymphoma is carried out through a peripheral catheter, central vein catheterization is performed under general anesthesia concurrently with diagnostic procedures. Obligatory monitoring of biochemical indicators for the timely detection of metabolic disorders.

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

In different countries, approximately equally effective programs for treatment of non-Hodgkin's lymphomas in children have been proposed. In Europe, these are the protocols of the BFM group (Germany, Austria) and the CFT (France). Widely used programs based on the protocols of the BFM group of 1990 and 1995, but, unfortunately, not always unified and correctly.

The treatment programs for different variants of non-Hodgkin's lymphomas are different. They depend on the histological structure and immunophenotype of the tumor. Lymphoblastic lymphomas from progenitor cells (predominantly T-, less often B-lines) should be treated equally, regardless of immunological affiliation. Other tactics are used in most children's non-Hodgkin's lymphomas with a more mature B-cell immunophenotype - Burkitt's lymphomas and B-large cell lymphomas. A separate protocol was proposed within the framework of the BFM for anaplastic large cell and peripheral T-cell lymphoma. Thus, the majority of 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's lymphomas.

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

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The main elements of programmatic polychemotherapy

Lymphoblastic lymphomas from progenitor cells, predominantly T-cell, less often non-Hodgkin's lymphoma from B-line cells:

• a long continuous course of polychemotherapy similar to treatment of acute lymphoblastic leukemia with the use of glucocorticosteroids, vincristine, cyclophosphamide, methotrexate, etc. (total duration 24-30 months);
• basic drugs - derivatives of anthracycline:
• 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 lesions include the mandatory endolumbar injections of cytostatics (cytarabine and methotrexate) and glucocorticosteroids at age doses, as well as cranial irradiation at a dose of 12-24 Gy in patients with stage III-IV lymphoma.

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

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

In the treatment of CNS lesions, the use of the Omayo reservoir is indicated. For patients at high risk (stage IV and B-cell acute lymphoblastic leukemia), in the absence of complete remission within a certain timeframe, it is necessary to solve the problem of the possibility of allogeneic or autologous transplantation of hematopoietic stem cells, the use of directed immunotherapy and other experimental approaches.

The drug rituximab (MabThera), which contains humanized anti-CD20 antibodies, appeared in recent years, showed good results in the treatment of aggressive B-cell adult lymphomas. The drug allowed to overcome the refractoriness of the tumor, without exerting a pronounced toxic effect on the patient. Studies are underway with the inclusion of rituximab in polychemotherapy programs in children with B-cell acute lymphoblastic leukemia, with refractory course and relapses of B-cell non-Hodgkin's lymphomas.

The protocol for the treatment of anaplastic large cell lymphoma practically repeats the above elements of course polychemotherapy without further 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 the IV stage of the disease, which is rarely observed with this type of lymphoma).

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

Treatment of recurrences of non-Hodgkin's lymphoma

Treatment of recurrence of non-Hodgkin's lymphoma is a difficult task, with Burkitt's lymphoma almost unpromising. In other variants of lymphomas, the effectiveness of treatment for relapse is also very low. In addition to intensive polychemotherapy, in the treatment of relapses it is possible to use experimental methods - immunotherapy with antibodies against tumor B cells (rituximab) and hematopoietic stem cell transplantation.

Protocols for treatment of children's lymphomas include detailed development of diagnostic and therapeutic measures, taking into account the features of the course of the disease, possible urgent situations, as well as recommendations for assessing the effectiveness of ongoing treatment and dynamic monitoring of patients after it is completed. The implementation of program therapy is possible with strict adherence to not only the regimes of polychemotherapy, but also the whole complex of the above measures in the conditions of specialized departments in the multidisciplinary highly qualified children's hospitals. Only this approach allows to obtain good results of treatment for non-Hodgkin's lymphoma - high-grade and one of the most frequent oncological diseases of childhood.