The aim of the trial is to evaluate the molecular characteristics and MDD/MRD of B-NHL in pediatric patients in order to identify on the one hand the very high risk group and to prescribe them more intensive treatment on the other hand to identify those patients who don't need very aggressive therapy. One more study question is to evaluate the role of PET/CT in assessment of the completeness of remission.
The following primary study questions are going to be analyzed:
* the effectiveness (event-free survival) in pediatric patients with very limited mature B-NHL (R1 - stage I and II R) of substituting anthracyclines and vincristine by the rituximab without compromising survival rates. * the effectiveness (event-free survival) in pediatric patients with limited mature B-NHL (R2 - stage I and II NR) of substituting anthracyclines by the rituximab without compromising survival rates. * the effectiveness (event-free survival) in pediatric patients with advanced VHR mature B-NHL (R4 - stages with unfavourable genetics of substituting standard chemotherapy by "second-line" block VICI in order to improve results
Secondary study questions will address
* additional parameters for immune reconstitution, lymphocyte subpopulations, immunoglobulin levels, vaccination titers and infection rates * kinetics of immune reconstitution after treatment
Age at diagnosis 0 to 18 years.
The diagnosis of Burkitt's lymphoma, Diffuse large B-cell lymphom, primary mediastinal lymphoma, primary CNS lymphoma, B-cell (Burkitt) AL
Informed consent of the patient parents (guardians) to be treated
previous malignancy, prior organ transplant, HIV infection or AIDS or severe immunodeficiency
hypersensitivity to rituximab or to ingredients of other IMPs.
no informed consent of the patient parents (guardians) to be treated
Parallel
Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate
DrugFor patients with very limited disease (R1- stage I/II СR), the addition of rituximab might allow the omission of anthracyclines and vincristine without jeopardizing survival rates but reducing acute and long term toxicities. In this treatment arm, it is tested whether the event-free survival is similar to that of the historical control
Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate, Vincristine
DrugR2: Drug: Rituximab 2 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, 2 doses of Rituximab before the start of the second chemotherapy cycle
Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, vincristine
Drug2 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, 2 doses of Rituximab before the start of the second
Cyclophosphamide , Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, Vincristine, Сarboplatine, CCNU/ BCNU, Melphalan, Idarubicin
DrugRituximab 4 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, Further
Event-free survival
Event-free survival The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.
Event-free survival
Event-free survival The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.
assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol
assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol
assessment of PET-CT results - initial and control points (early PET response).after the 2nd block
measurement of tumor volume at diagnosis and measurement of tumor volume reduction after therapy in percent after the 2nd block - CT with CL of the involved areas, PET-CT examination on the 14th day (maximum on the 17th day) after the last injection of CT, IPT, MRD in the bone marrow
assessment of PET-CT results - initial and control points (early PET response) after 4th block
measurement of tumor volume at diagnosis and measurement of tumor volume reduction after therapy in percent after 4th block - CT with the CL of the involved areas , PET-CT examination on the 14th day (maximum on the 17th day) after the last administration of CT, MRD in the bone marrow if present after the 2nd block After the 6th block - CT with CL of the involved areas
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