Publications by authors named "Dmitriy Konovalov"

3 Publications

  • Page 1 of 1

BCG-Related Inflammatory Syndromes in Severe Combined Immunodeficiency After TCRαβ+/CD19+ Depleted HSCT.

J Clin Immunol 2020 05 6;40(4):625-636. Epub 2020 May 6.

Department of Immunology, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, 1, Samory Mashela str., Moscow, Russia, 117997.

Introduction: The live-attenuated BCG vaccine is known to cause disseminated Mycobacterium bovis infection in patients with severe combined immunodeficiency (SCID). However, BCG-related post-hematopoietic stem cell transplantation (HSCT) immune reconstitution inflammatory syndromes, similar to those described in patients with HIV infections, are less-known complications of SCID.

Patients And Methods: We reported on 22 BCG-vaccinated SCID patients who had received conditioned allogeneic HSCT with TCRαβ+/CD19+ graft depletion. All BCG-vaccinated patients received anti-mycobacterial therapy pre- and post-HSCT. Post-transplant immunosuppression consisted of tacrolimus in 10 patients and of 8 mg/kg tocilizumab (d-1, + 14, + 28) and 10 mg/kg abatacept (d-1, + 5, + 14, + 28) in 11 patients.

Results: Twelve patients, five of whom had BCG infection prior to HSCT, developed BCG-related inflammatory syndromes (BCG-IS). Five developed early BCG-IS with the median time of manifestation 11 days after HSCT, corresponding with a dramatic increase of CD3+TCRγδ+ in at least two patients. Early BCG-IS was noted in only one out of 11 patients who received tocilizumab/abatacept and 4 out of 11 patients who did not. Seven patients developed late BCG-IS which corresponded to T cell immune recovery; at the time of manifestation (median 4.2 months after HSCT), the median number of CD3+ cells was 0.42 × 10/ and CD3+CD4+ cells 0.27 × 10/l. In all patients, late BCG-IS was controlled with IL-1 or IL-6 inhibitors.

Conclusion: BCG-vaccinated SCID patients undergoing allogeneic HSCT with TCRαβ+/CD19+ graft depletion are at an increased risk of early and late BCG-IS. Anti-inflammatory therapy with IL-1 and IL-6 blockade is efficient in the prevention of early and treatment of late BCG-IS.
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May 2020

Therapy of advanced-stage mature B-cell lymphoma and leukemia in children and adolescents with rituximab and reduced intensity induction chemotherapy (B-NHL 2004M protocol): the results of a multicenter study.

J Pediatr Hematol Oncol 2014 Jul;36(5):395-401

*Federal Research Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev †Russian Pediatric Clinical Hospital, Moscow ‡Municipal Clinical Hospital No. 31, Saint-Petersburg §Regional Pediatric Clinical Hospital, Yekaterinburg ∥Regional Pediatric Clinical Hospital, Nizhniy Novgorod ¶Territorial Pediatric Clinical Hospital, Perm, Russia.

Pediatric mature B-cell non-Hodgkin lymphomas (B-NHLs) are highly aggressive malignant tumors that are curable with chemotherapy (ChT). High-dose methotrexate (MTX) is considered indispensable for successful treatment, but this therapy frequently induces severe mucositis and infectious complications, especially in induction, which can cause treatment failure. A prospective multicenter trial of combined immunochemotherapy for advanced-stage B-NHL with rituximab and the modified NHL-BFM-90 protocol was conducted. The major differences from the original protocol were a decrease in the dose of MTX from 5000 to 1000 mg/m/24 h in the first 2 ChT blocks and the addition of rituximab at 375 mg/m to each of the first 4 blocks of ChT. Eighty-three newly diagnosed patients with a median age of 8.84 years with Burkitt lymphoma/leukemia and diffuse large B-cell lymphomas stage III to IV were included. Four patients died during induction ChT due to tumor lysis syndrome and infection. Two additional patients died subsequently due to tumor resistance. Complete remission was achieved in 77 (92.8%) patients; 2 patients relapsed at 1 and 3 months, and 2 developed secondary malignancies at 1 and 6.5 years, respectively, after the completion of therapy. The overall survival probability was 82%±8% with a median follow-up of 65.2 months. Combined therapy with rituximab and intensive ChT with a reduced MTX dose of 1 g/m in the 2 induction courses was feasible and produced high cure rates in patients with pediatric advanced-stage mature B-NHL.
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July 2014

Expression of CD8 is associated with non-common type morphology and outcome in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma.

Haematologica 2013 Oct 28;98(10):1547-53. Epub 2013 May 28.

Anaplastic lymphoma kinase-positive anaplastic large T-cell lymphoma is characterized by morphological variability. Morphological variants (non-common subtype) are associated with a poor outcome. They display abundant reactive bystander cells admixed with the lymphoma cells. So far, the difficulty in distinguishing lymphoma cells from bystander cells by visual inspection has prevented detailed and reliable immunophenotypic analysis using conventional immunohistochemistry. To overcome these limitations, we analyzed 124 cases of pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma treated within clinical trials using immunofluorescence multi-staining and digital image analysis combining antibodies against anaplastic lymphoma kinase to specifically identify lymphoma cells with antibodies against CD30, CD3, CD5, CD8, Ki67 and phosphorylated STAT3. Non-common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas express CD8 more frequently than common type anaplastic lymphoma kinase-positive anaplastic large cell lymphomas (35.4% and 5.6%, respectively; P=0.0002). CD8 expression was associated with a poorer outcome. Importantly, in a multivariate analysis including clinical risk factors, histological subtype and CD8 expression, CD8-positivity proved to be an independent prognostic predictor of worse outcome (hazard ratio for survival 3.38, P=0.042).
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October 2013