title: TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia.
abstract: 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.
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: M
authors.initials: M
authors.lastname: Maschan
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: L
authors.initials: L
authors.lastname: Shelikhova
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: M
authors.initials: M
authors.lastname: Ilushina
authors.affiliation: Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: E
authors.initials: E
authors.lastname: Kurnikova
authors.affiliation: Laboratory of hematopoietic stem cell transplantation biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: E
authors.initials: E
authors.lastname: Boyakova
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: D
authors.initials: D
authors.lastname: Balashov
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: M
authors.initials: M
authors.lastname: Persiantseva
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: Y
authors.initials: Y
authors.lastname: Skvortsova
authors.affiliation: Department of hematopoietic stem cell transplantation, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: A
authors.initials: A
authors.lastname: Laberko
authors.affiliation: Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: Y
authors.initials: Y
authors.lastname: Muzalevskii
authors.affiliation: Blood bank and hematopoietic stem cell processing laboratory, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: A
authors.initials: A
authors.lastname: Kazachenok
authors.affiliation: Laboratory of hematopoietic stem cell transplantation biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: S
authors.initials: S
authors.lastname: Glushkova
authors.affiliation: Laboratory of molecular biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Bobrynina
authors.affiliation: Laboratory of molecular biology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Kalinina
authors.affiliation: Laboratory of cytogenetics and molecular genetics, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: Y
authors.initials: Y
authors.lastname: Olshanskaya
authors.affiliation: Department of pediatric hematology and oncology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: D
authors.initials: D
authors.lastname: Baidildina
authors.affiliation: Department of pediatric hematology and oncology, Dmitriy Rogachev Federal center for pediatric hematology, oncology and immunology, Moscow, Russia.
authors.forename: G
authors.initials: G
authors.lastname: Novichkova
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Maschan
mesh_terms: D000293:Adolescent; D018941:Antigens, CD19 / Q000032:analysis* / Q000302:isolation & purification; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000302:isolation & purification; D019172:Transplantation Conditioning / Q000379:methods*; D000075442:Transplantation, Haploidentical / Q000379:methods* / Q000401:mortality; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D016693:Receptors, Antigen, T-Cell, alpha-beta; C018404:treosulfan; D002066:Busulfan