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Br J Haematol. 2019 May 28. doi: 10.1111/bjh.15970. [Epub ahead of print]

Allodepleted T-cell immunotherapy after haploidentical haematopoietic stem cell transplantation without severe acute graft-versus-host disease (GVHD) in the absence of GVHD prophylaxis.

Author information

1
Division of Hematology-Oncology/Stem Cell Transplantation, Hôpital Maisonneuve-Rosemont Research Center, Montreal, Canada.
2
Department of Medicine, Université de Montréal, Montreal, Canada.
3
Department of Biostatistics, Montreal Health Innovations Coordinating Center, Montreal, Canada.
4
Department of Stem Cell Transplant and Cellular Therapy, M.D. Anderson Cancer Center, University of Texas, Houston, TX, USA.
5
Department of Internal Medicine II, Center of Allogeneic Stem Cell Transplantation, Wuerzburg University Medical Center, University of Wuerzburg, Wuerzburg, Germany.
6
Department of Laboratory Medicine, CAST, Karolinska Institute and University Hospital, Stockholm, Sweden.

Abstract

Graft-versus-host disease (GVHD) is a major cause of transplant-related mortality (TRM) after allogeneic haematopoietic stem cell transplantation (HSCT) and presents a challenge in haploidentical HSCT. GVHD may be prevented by ex vivo graft T-cell depletion or in vivo depletion of proliferating lymphocytes. However, both approaches pose significant risks, particularly infections and relapse, compromising survival. A photodepletion strategy to eliminate alloreactive T cells from mismatched donor lymphocyte infusions (enabling administration without immunosuppression), was used to develop ATIR101, an adjunctive therapy for use after haploidentical HSCT. In this phase I dose-finding study, 19 adults (median age: 54 years) with high-risk haematological malignancies were treated with T-cell-depleted human leucocyte antigen-haploidentical myeloablative HSCT followed by ATIR101 at doses of 1 × 104 -5 × 106  CD3+  cells/kg (median 31 days post-transplant). No patient received post-transplant immunosuppression or developed grade III/IV acute GVHD, demonstrating the feasibility of ATIR101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long-term follow -up of patients treated with ATIR101 in this study. At 1 year, all 9 patients receiving doses of 0·3-2 × 106  CD3+  cells/kg ATIR101 remained free of serious infections and after more than 8 years, TRM was 0%, relapse-related mortality was 33% and overall survival was 67% in these patients.

KEYWORDS:

cell therapy and immunotherapy; graft-versus-host-disease; haematopoietic stem cell; stem cell transplantation

PMID:
31135970
DOI:
10.1111/bjh.15970

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