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

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.558-558
• Main Authors: Shelikhova, Larisa, Bogoyavlenskaya, Anna, Ilushina, Maria, Salimova, Tatiana, Antonova, Kristina, Skvortsova, Julia, Shasheleva, Daria, Radygina, Svetlana, Sultanova, Elvira, Glushkova, Svetlana, Nikolaev, Ruslan, Kurnikova, Elena, Pershin, Dmitry, Muzalevsky, Yakov, Kazachenok, Alexey, Osipova, Elena, Balashov, Dmitriy, Novichkova, Galina, Maschan, Alexey, Maschan, Michael
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-152769

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