HEMATOLOGIC MALIGNANCIES: DIAGNOSIS, TREATMENT, SUPPORTIVE CARE
The results of two consecutive multicenter clinical trials enrolled 241 patient with childhood mature B-cells non-Hodgkin lymphomas/leukemia are presented. Patients received treatment according B-NHL 2004mab protocol (n = 83) and B-NHL 2010M (n = 158) with combined immunochemotherapy (ICT) in Russian and Belarus pediatric clinics from 2004 to 2015 years. Primary patients with different mature B-NHL (Burkitt lymphoma/leukemia, diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma (DLBCL and PMBCL)) aged from 2 to 18 years are included in the studies.
Protocol B-NHL 2004mab for treatment of children and adolescents with B-NHL/B-AL, stage III and IV, includes a combination of chemotherapy (PCT) and rituximab – an antibody against the B-cells receptor CD20. PCT courses similar to those in the B-NHL BFM90 protocol (group III) with the exception of methotrexate dose in induction courses, reduced to 1 g/m2 /24 h in order to reduce toxicity. Rituximab (Mabthera, 375 mg/m2 /h) used for the first time in the treatment of children and adolescents with B-NHL. Of the 83 patients included, clinical remission was achieved in 77 (92.8 %). With a median follow time of 51.6 months, remission continued in 23 (85.2 %) patients with B-AL, in 32 (88.9 %) patients with LB and 19 (95.0 %) patients – with DLBCL. With median follow time of 65.2 months, event-free and overall survival was 84 ± 6 and 82 ± 8 %, respectively.
Based on previous experience in order to further optimize B-NHL treatment, new protocol B-NHL 2010M with effect-adapted therapy and improvement of stratification risk group criteria was proposed. Overall survival in patients of 1st and 2nd risk groups with full implementation of diagnosis and treatment is approaching 100 %. In interim analysis of 3rd risk group patients, pOS was 88 ± 3 %. The incidence of induction death (infections, metabolic complications) remains within 2.7 % (n = 4); refractory cases (n = 2; 1.3 %) and relapses (n = 4; 2.7 %) developed after 2–4 months of remission, were observed only in patients with Burkitt lymphoma/leukemia. In this cases 2nd line therapy and auto-HSCT is not allowed to achieve remission. All PMBCL and DLBCL patients were achieved remission, but in 50 % of cases only after second line, radio- and cell therapy.
The authors conclude that a combined immunochemotherapy of B-NHL in children and adolescents, including the target drug (rituximab) and 5-day courses of cytostatic therapy, highly effective, despite a reduce induction intensity. Therapy for the analyzed protocol requires qualitative dynamic efficacy monitoring and timely correction of therapy. In order to solve a refractory problem and further reduce the toxicity, necessary to continue research using fundamental discoveries in recent years.
Glomerulonephritis associated with marginal zone B-cell lymphoma at the onset of disease is rarely diagnosed. In this article we reported two patient of the extranodal marginal zone B-cell lymphoma with kidney damage. The first patient with the extranodal marginal zone B-cell lymphoma involved the stomach, lymph nodes, bone marrow and associated with mesangioproliferative glomerulonephritis and renal failure. The second patient with the splenic form of marginal zone B-cell lymphoma associated with fibrillary glomerulonephritis and hepatitis C and involve the lymph nodes, liver, bone marrow, and synthesis monoclonal immunoglobulin (IgMκ), cryoglobulin type II. Glomerulonephritis of the both cases were established on the renal biopsies by the morphological investigation, immunofluorescence, and electron microscopy.
Both patients received therapy with bendamustine and rituximab, which has resulted in complete remission for lymphatic tumors and improve of kidney function. Overall and event-free survival in the first case corresponds to 21 and 16 months, the second 29 and 20, respectively.
These cases illustrates that the kidney may be initially involved by extranodal marginal zone B-cell lymphoma, and the need for expanded investigation of the possible dissemination. Combination of bendamustine and rituximab were effective and safety treatment in these cases.
Splenic B-cell marginal zone lymphoma (SMZL) – a rare B-cell non-Hodgkin, s lymphoma, which is represented morphologically by mature lymphoid cells, corresponding to lymphocytes of secondary follicles marginal zone by immunological characteristics. Plasma cell differentiation can be in marginal zone lymphoma, but we described a single case of abundance of Mott cells as a tumor substrate in splenic B-cell marginal zone lymphoma.
We present the first case of SMZL represented by Mott cells. This was the second case of Mott cells tumor described in Russia.
This observation is the only case among the collected material of splenic lymphomas. The morphological pattern is characterized by marked proliferation of monoclonal lymphoid cells with plasma cell differentiation with presence of Mott cells and is evidence of intense intracellular secretion of immunoglobulins.
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