TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia.

Autor: Maschan M; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Shelikhova L; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Ilushina M; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Kurnikova E; Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Boyakova E; Laboratory of hematopoietic stem cell transplantation biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Balashov D; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Persiantseva M; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Skvortsova Y; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Laberko A; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Muzalevskii Y; Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Kazachenok A; Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Glushkova S; Laboratory of hematopoietic stem cell transplantation biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Bobrynina V; Laboratory of molecular biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Kalinina V; Laboratory of molecular biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Olshanskaya Y; Laboratory of cytogenetics and molecular genetics, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Baidildina D; Department of pediatric hematology and oncology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Novichkova G; Department of pediatric hematology and oncology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia., Maschan A; Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.; Department of pediatric hematology and oncology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
Jazyk: angličtina
Zdroj: Bone marrow transplantation [Bone Marrow Transplant] 2016 May; Vol. 51 (5), pp. 668-74. Date of Electronic Publication: 2016 Jan 25.
DOI: 10.1038/bmt.2015.343
Abstrakt: We evaluated the depletion of TCR-alpha/beta cells from the graft of children with high-risk AML, who received transplantation from unrelated (n=20) and haploidentical donors (n=13). The preparative regimen included treosulfan, melphalan, fludarabine and anti-thymocyte globulin. Grafts were PBSC engineered by TCR-alpha/beta and CD19 depletion. The graft contained a median of 9 × 10(6)/kg of CD34+ and 20 × 10(3)/kg of αβ-T cells. Post-transplant immune suppression included tacrolimus till day +30 and Mtx in 21 patients, tacrolimus in 5, Mtx in 2 and no prophylaxis in 5 patients. Sixteen patients received native or TCR-alpha/beta-depleted donor lymphocytes at a median of 47 (40-204) days. Median follow-up is 1.76 years. Primary engraftment was achieved in 33 patients (100%). Cumulative incidence of acute GvHD (aGvHD) grade 2-3 was 39 (26-60)%, half of them had skin-only aGvHD. Cumulative incidence of chronic GvHD was 30(18-50)%. Transplant-related mortality is 10(4-26)%. Event-free survival (EFS) is 60(43-76)% and overall survival (OS) is 67(50-84)% at 2 years. In a subgroup of patients, who received transplantation in CR, EFS is 66(48-84)% and OS-72(53-90)% at 2 years. Our data suggest that TCR-alpha/beta and CD19 depletion is a robust method of graft manipulation, which can be used to engineer grafts for children with AML.
Databáze: MEDLINE
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