Results of Hematopoietic Stem Cells Transplantation with Tcrαβ and CD19-Depletion from Matched Related Donors and Infusions of CD45RA Depleted Donor Lymphocytes in Pediatric Severe Aplastic Anemia

Autor: Maria Ilushina, Elvira Sultanova, Larisa Shelikhova, Svetlana Glushkova, Alexey Kazachenok, Elena Kurnikova, Kristina S. Antonova, Ruslan Nikolaev, Anna Bogoyavlenskaya, Galina Novichkova, Michael Maschan, Dmitriy Balashov, Elena Osipova, Tatiana Salimova, Julia Skvortsova, Yakov Muzalevsky, Alexey Maschan, Daria Shasheleva, Dmitry Pershin, Svetlana Radygina
Rok vydání: 2021
Předmět:
Zdroj: Blood. 138:558-558
ISSN: 1528-0020
0006-4971
Popis: Introduction HSCT from matched family donors results in most favorable outcomes among children with severe aplastic anemia (SAA). Despite overall success, morbidity, associated with acute and chronic graft-versus-host disease (GVHD) is not completely prevented with current standard of pharmacologic prophylaxis. Depletion of ab T cells from the graft prevents GVHD, and improves outcome of hematopoietic stem cell transplantation from haploidentical donors, while infusions of donor memory lymphocytes (mDLI) (CD45RA-depleted) are able to transfer pathogen-specific immunity without the risk of GVHD. We evaluated the outcomes of ab T cell depletion and add-back of intermediate-dose mDLI among the pediatric SAA recipients of matched related grafts. Materials and methods A total of 16 children with SAA (8 female, 8 male, median age 10,9 y) underwent allogenic HSCT from matched family donors (MFD) between february 2015 and may 2021. For 15 (94%) pts it was the first allo HSCT, for 1 pts it was the second HSCT. TCR αβ+/CD19+ depletion of HSCT with CliniMACS technology was implemented in all cases. The median dose of CD34+ cells was 7,1 x10 6/kg (range 2,6-13), αβ T cells - 28x10 3/kg (range 5,6-184). All pts received an additional injection of memory T-cell (CD45RA-depleted) on day 0 at 1 million T cells per kg. All patients received cyclophosphamide at 100 mg/kg, fludarabine at 100 mg/m 2, rituximab 100mg/m 2 and serotherapy with either rabbit ATG at 5 mg/kg (n-2) or horse ATG at 100 mg/kg (n-14). Post-transplant GVHD prophylaxis included calcineurin (CNI)-based regimen and abatacept 10mg/kg on days -1, +7, +14 and +28. All pts received a graft from a 10/10 HLA-matched sibling. Median time of follow-up for survivors was 1,1 years (range: 0.14 - 6.38). Results Primary engraftment was achieved in all evaluable patients (100%) with full donor chimerism, and the median time to neutrophil and platelet recovery was 11 (10-20) and 14 (11-20) days, respectively. One patient had aGVHD grade I, there were no incidence of grade II-IV aGVHD and TRM. Event-free and overall survival were 100%. CMV viremia was detected among two patients after a median of 40 (35-73) days after HSCT. No cases of ADV and Epstein-Barr virus (EBV) viremia and EBV disease were recorded. The median recovery of T cells on day+60 was 0,26 (0,04-0,9). Conclusion ab T cell-depleted transplantation with intermediate dose memory T cell add-back definitively prevents GVHD and provides a platform for safe HSCT from matched family donors in patients with SAA. Disclosures Maschan: Miltenyi Biotec: Speakers Bureau.
Databáze: OpenAIRE
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