Publications by authors named "Dmitry Pershin"

5 Publications

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Plerixafor added to G-CSF allows mobilization of a sufficient number of hematopoietic progenitors without impacting the efficacy of TCR-alpha/beta depletion in pediatric haploidentical and genoidentical donors failing to mobilize with G-CSF alone.

J Clin Apher 2021 Mar 8. Epub 2021 Mar 8.

Dmitri Rogachev National Research Centre for Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russian Federation, Moscow, Russia.

Background: Collection of a large number of early hematopoietic progenitors is essential for allogeneic apheresis products intended for TCR-alpha/beta depletion.

Materials And Methods: We added plerixafor 0.24 mg/kg body weight (bw) on day 4 of high-dose filgrastim mobilization 10 hours prior to apheresis in 16 (30.5%) pediatric allogeneic donors who failed to recover a sufficient number of CD34+ cells.

Results: On day 4 of G-CSF, the median CD34+ cell count in peripheral blood was 6 per μL (range 4-9 per μL) in 6 poor mobilizers and 16 per μL (range 12-19 per μL) in insufficient mobilizers. In all donors, the threshold of 50 CD34+ cells/μL was achieved, and the median increase was 14.8-fold in poor mobilizers and 6.5-fold in insufficient mobilizers, whereas it was 3.45-fold increase in those mobilized with G-CSF alone.

Discussion: In all donors, a predefined number of >10 × 10 CD34+ cells/kg of recipient bw before depletion was reached in the apheresis product. The use of plerixafor did not affect the purity of further TCR-alpha/beta depletion. Side effects were mild to moderate and consisted of nausea and vomiting.

Conclusion: Thus, the safety and high efficacy of plerixafor was proven in healthy pediatric allogeneic hematopoietic cell donors.
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http://dx.doi.org/10.1002/jca.21891DOI Listing
March 2021

Efficacy of romiplostim in treatment of thrombocytopenia in children with Wiskott-Aldrich syndrome.

Br J Haematol 2021 01 31;192(2):366-374. Epub 2020 Oct 31.

Department of Immunology, Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Wiskott-Aldrich syndrome (WAS) is a life-threatening primary immunodeficiency associated with bleeding of variable severity due to thrombocytopenia. Correction of the thrombocytopenia is of paramount importance for most WAS patients. We report a retrospective analysis of the safety and efficacy of romiplostim treatment in reducing thrombocytopenia and bleeding tendency in 67 children (median age 1·3 years) with genetically confirmed WAS, followed in eight months (range, 1-12 months). Complete or partial primary responses regarding platelet counts were observed in 22 (33%) and 18 (27%) subjects, respectively. Yet, even in the non-responder group, the risk of haemorrhagic events decreased significantly, to 21%, after the first month of treatment. The responses tended to be durable and stable over time, with no significant fluctuations in platelets counts. The results of this retrospective study of a large cohort of WAS patients demonstrates that romiplostim can be used to increase platelet counts and reduce the risks of life-threatening bleeding in WAS patients awaiting haematopoietic stem cell transplantation or forgoing the procedure for various reasons.
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http://dx.doi.org/10.1111/bjh.17174DOI Listing
January 2021

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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http://dx.doi.org/10.1007/s10875-020-00774-xDOI Listing
May 2020

Control of graft-versus-host disease with rabbit anti-thymocyte globulin, rituximab, and bortezomib in TCRαβ/CD19-depleted graft transplantation for leukemia in children: a single-center retrospective analysis of two GVHD-prophylaxis regimens.

Pediatr Transplant 2020 02 3;24(1):e13594. Epub 2019 Nov 3.

Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.

Both acute GVHD and chronic GVHD remain the leading cause of morbidity and death after allogeneic HSCT. We conducted a retrospective analysis comparing two GVHD-prophylaxis regimens: 35 patients received "Regimen 1" (horse ATG, tacrolimus, and methotrexate) and 46 "Regimen 2" (rabbit ATG, rituximab, and peritransplant bortezomib). All 81 patients with a median age of 9 (0.6-23) years with ALL (n = 31) or AML (n = 50) in complete remission received TCRαβ/CD19-depleted transplants between May 2012 and October 2016, from 40 HLA-matched unrelated and 41 haploidentical donors. After a median follow-up of 3.9 years, the CI of acute GVHD II-IV was 15% (95% CI: 7-30) in the "Regimen 2" group and 34% (95% CI: -54) in the "Regimen 1" group, P = .05. "Regimen 2" was also more effective in the prevention of chronic GVHD; the CI at 1 year after HSCT was 7% (95% CI: 2-19) vs 31% (95% CI: 19-51), P = .005. The CI of relapse at 3 years adjusted for the GVHD-prophylaxis regimen groups 31% (95% CI: 19-51) for the "Regimen 1" vs 21% (95% CI: 11-37) for the "Regimen 2", P = .3. The retrospective observation suggests that the use of the rATG, rituximab, and bortezomib was associated with significantly lower rate of GVHD without the loss of anti-leukemic activity.
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http://dx.doi.org/10.1111/petr.13594DOI Listing
February 2020

Natural products as templates for bioactive compound libraries: synthesis of biaryl derivatives of (+/-)-vasicine.

Nat Prod Res 2006 Jul;20(8):735-41

Chemical Diversity Research Institute, Khimki, Moscow Reg., 114401 Russia.

A reliable and high-yielding procedure for preparation of 7-aryl and 7-heteroaryl derivatives of (+/-)-vasicine in two steps from the naturally occurring material is described. This protocol broadens the chemical space for selective modifications of the vasicine tricyclic structure, thereby making it a valuable starting point for the development of novel compound libraries with potentially beneficial biological profiles.
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http://dx.doi.org/10.1080/14786410500247418DOI Listing
July 2006
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