Publications by authors named "Alexey A Maschan"

8 Publications

  • Page 1 of 1

Thrombopoietin receptor agonist switch in children with persistent and chronic severe immune thrombocytopenia: A retrospective analysis in a large tertiary center.

Pediatr Blood Cancer 2019 06 11;66(6):e27704. Epub 2019 Mar 11.

Dmitri Rogachev National Research Center for Pediatric Hematology, Oncology and Immunology, Moskva, Russia.

We retrospectively analyzed sequential therapy with romiplostim and eltrombopag in 23 children with immune thrombocytopenia: switching from romiplostim to eltrombopag (10 patients) or vice versa (13 patients). The median age of patients at enrollment in the study was 5.6 years (2-15 years). Switching from romiplostim to eltrombopag was effective in eight (80%) patients, whereas switching from eltrombopag to romiplostim was effective in eight (62%) patients. The response rate was similar in patients failing the first thrombopoietin receptor agonist and those who had previous response. To date, all responders continue to maintain platelets over 50 × 10 /L at 13-39 months after switching.
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http://dx.doi.org/10.1002/pbc.27704DOI Listing
June 2019

Prospective Study of a Cohort of Russian Nijmegen Breakage Syndrome Patients Demonstrating Predictive Value of Low Kappa-Deleting Recombination Excision Circle (KREC) Numbers and Beneficial Effect of Hematopoietic Stem Cell Transplantation (HSCT).

Front Immunol 2017 24;8:807. Epub 2017 Jul 24.

Dmitry Rogachev National Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Background: Nijmegen breakage syndrome (NBS) is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Due to the rarity of the disease in the rest of the world, studies of NBS patients are few. Here, we report a prospective study of a cohort of Russian NBS patients.

Methods: 35 Russian NBS patients of ages 1-19 years, referred to our Center between years 2012 and 2016, were prospectively studied.

Results: Despite the fact that in 80% of the patients microcephaly was diagnosed at birth or shortly thereafter, the average delay of NBS diagnosis was 6.5 years. Though 80% of the patients had laboratory signs of immunodeficiency, only 51% of the patients experienced significant infections. Autoimmune complications including interstitial lymphocytic lung disease and skin granulomas were noted in 34%, malignancies-in 57% of the patients. T-cell excision circle (TREC)/kappa-deleting recombination excision circle (KREC) levels were low in the majority of patients studied. Lower KREC levels correlated with autoimmune and oncological complications. Fifteen patients underwent hematopoietic stem cell transplantation (HSCT), 10 of them were alive and well, with good graft function. Three patients in the HSCT group and five non-transplanted patients died; tumor progression being the main cause of death. The probability of the overall survival since NBS diagnosis was 0.76 in the HSCT group and 0.3 in the non-transplanted group.

Conclusion: Based on our findings of low TRECs in most NBS patients, independent of their age, TREC detection can be potentially useful for detection of NBS patients during neonatal screening. KREC concentration can be used as a prognostic marker of disease severity. HSCT is a viable treatment option in NBS and should be especially considered in patients with low KREC numbers early on, before development of life-threatening complications.
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http://dx.doi.org/10.3389/fimmu.2017.00807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523727PMC
July 2017

Eight-year follow-up in pediatric living donor kidney recipients receiving alemtuzumab induction.

Pediatr Transplant 2017 Aug 10;21(5). Epub 2017 Jun 10.

Laboratory Department, Boris Petrovsky Research Center of Surgery, Moscow, Russia.

Recipient lymphocytes are crucial for direct and indirect pathways of allorecognition. We proposed that the administration of alemtuzumab several weeks pretransplantation could eradicate peripheral lymphatic cells and promote donor-specific acceptance. This was a single-center, retrospective review of 101 consecutive living donor kidney transplantations in pediatric patients (age 7 months-18 years), performed between September 2006 and April 2010. IS protocol included two 30 mg doses of alemtuzumab: The first was given 12-29 days prior to transplantation, and the second at the time of transplantation. Maintenance IS was based on combination of low-dose CNI and mycophenolate, with steroids tapered over the first 5 days post-transplantation. Patients were followed for 7.8±1.3 years, and protocol biopsies were taken 1 month, 1, 3, and 5 years post-transplant. The Kaplan-Meier 8-year patient and graft survival rates in the cyclosporine-treated patients were 82.0±7.3% and 71.6±7.3, and in the tacrolimus-treated patients were 97.2±5.4 and 83.8±6.0%. Biopsy-proven acute rejection developed in 35% of cyclosporine-treated patients and in 8% of tacrolimus-treated patients. Alemtuzumab pretreatment prior to LRD kidney transplantation, followed by maintenance immunosuppression with tacrolimus and MMF, is associated with reasonable long-term results in pediatric patients.
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http://dx.doi.org/10.1111/petr.12941DOI Listing
August 2017

Clinical and genomic heterogeneity of Diamond Blackfan anemia in the Russian Federation.

Pediatr Blood Cancer 2015 Sep 6;62(9):1597-600. Epub 2015 May 6.

Dmitry Rogachev Federal Clinical Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Background: Diamond Blackfan anemia (DBA) is a genetically and clinically heterogeneous ribosomopathy and inherited bone marrow failure syndrome characterized by anemia, reticulocytopenia, and decreased erythroid precursors in the bone marrow with an increased risk of malignancy and, in approximately 50%, physical abnormalities.

Methods: We retrospectively analyzed clinical data from 77 patients with DBA born in the Russian Federation from 1993 to 2014. In 74 families there was one clinically affected individual; in only three instances a multiplex family was identified. Genomic DNA from 57 DBA patients and their first-degree relatives was sequenced for mutations in RPS19, RPS10, RPS24, RPS26, RPS7, RPS17, RPL5, RPL11, RPL35a, and GATA1.

Results: Severe anemia presented before 8 months of age in all 77 patients; before 2 months in 61 (78.2%); before 4 months in 71 (92.2%). Corticosteroid therapy was initiated after 1 year of age in the majority of patients. Most responded initially to steroids, while 5 responses were transient. Mutations in RP genes were detected in 35 of 57 patients studied: 15 in RPS19, 6 in RPL5, 3 in RPS7, 3 each in RPS10, RPS26, and RPL11 and 1 each in RPS24 and RPL35a; 24 of these mutations have not been previously reported. One patient had a balanced chromosomal translocation involving RPS19. No mutations in GATA1 were found.

Conclusion: In our cohort from an ethnically diverse population the distribution of mutations among RP genes was approximately the same as was reported by others, although within genotypes most of the mutations had not been previously reported.
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http://dx.doi.org/10.1002/pbc.25534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515145PMC
September 2015

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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http://dx.doi.org/10.1097/MPH.0b013e31829d4900DOI Listing
July 2014

Alemtuzumab induction in pediatric kidney transplantation.

Pediatr Transplant 2013 Mar;17(2):168-78

Organ Transplant Division, Russian Scientific Center of Surgery, Moscow, Russia.

Recipient parenchymal lymphatic cells are crucial for direct and indirect pathways of allorecognition. We proposed that alemtuzumab, being infused several weeks pretransplant could eradicate peripheral lymphatic cells and promote donor-specific tolerance. We present here a single center, retrospective review of 101 consecutive living-donor kidney transplantations to pediatric patients aged from seven month to 18 yr, performed between September 2006 and April 2010. Immunosupression protocol included two 30 mg doses of alemtuzumab: first given 12-29 d prior to transplantation and second at the time of transplantation. Maintenance immunosupression was based on combination of low dose and wide range CNI and mycophenolate. Patients were followed for 3.8 ± 1.4 yr and protocol biopsies were taken one month, one, and three yr post transplant. The Kaplan-Meier graft and patient survival was 96% and 97% for one yr, 89% and 93% for three yr. Biopsy proven acute rejection developed in 26% patients at one yr and in 35% at two yr, no rejections occurred beyond two yr. We conclude that alemtuzumab pretreatment prior to living related donor kidney transplantation allows to reach satisfactory middle-term results in pediatric patients with wide range and low CNI concentrations.
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http://dx.doi.org/10.1111/petr.12048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644867PMC
March 2013

Response of pure red cell aplasia to cyclophosphamide after failure of mycofenolate mofetil in a patient with polyglandular syndrome type I.

J Pediatr Hematol Oncol 2013 Nov;35(8):e338-40

*Endocrinology Research Centre, Institute of Pediatric Endocrinology †Federal Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russian Federation.

A 26-year-old female with the classic major and minor components of autoimmune polyglandular syndrome type 1 was diagnosed as having pure red cell aplasia. Treatment with 1.5 g/d mycofenolate mofetil for 3 months failed to restore erythroid production. Treatment with cyclosporine A produced a good partial response but led to renal toxicity and was therefore substituted with cyclophosphamide, which had a good partial effect and lasted for 18 months. The relapse of anemia was not observed during the 6-month follow-up period after the cessation of treatment.
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http://dx.doi.org/10.1097/MPH.0b013e3182755c52DOI Listing
November 2013

657del5 mutation in the gene for Nijmegen breakage syndrome (NBS1) in a cohort of Russian children with lymphoid tissue malignancies and controls.

Am J Med Genet A 2003 Jul;120A(2):174-9

Department of Immunology, Research Institute for Paediatric Hematology, Moscow, Russia.

Nijmegen breakage syndrome (NBS, OMIM 251260) is a rare hereditary disease, characterized by immune deficiency, microcephaly, and an extremely high incidence of lymphoid tissue malignancies. The gene mutated in NBS, NBS1, was recently cloned from its location on chromosome 8q21. The encoded protein, nibrin (p95), together with hMre11 and hRad50, is involved in the double-strand DNA break repair system. We screened two Russian cohorts for the 657del5 NBS1 mutation and found no carriers in 548 controls and two carriers in 68 patients with lymphoid malignancies: one with acute lymphoblastic leukemia (ALL) and one with non-Hodgkin lymphoma (NHL). Several relatives of the second patient, who were carriers of the same mutation, had cancer (ALL, breast cancer, GI cancers). These preliminary data suggest that NBS1 mutation carriers can be predisposed to malignant disorders.
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http://dx.doi.org/10.1002/ajmg.a.20188DOI Listing
July 2003
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