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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(s) -
Roy Denis Claude,
Lachance Sylvie,
Cohen Sandra,
Delisle JeanSébastien,
Kiss Thomas,
Sauvageau Guy,
Busque Lambert,
Ahmad Imran,
Bernard Lea,
Bambace Nadia,
Boumédine Radia S.,
Guertin MarieClaude,
Rezvani Katayoun,
Mielke Stephan,
Perreault Claude,
Roy Jean
Publication year - 2019
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15970
Subject(s) - immunosuppression , medicine , graft versus host disease , immunology , stem cell , transplantation , hematopoietic stem cell transplantation , haematopoiesis , donor lymphocyte infusion , immunotherapy , immune system , biology , genetics
Summary 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 ATIR 101, 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 ATIR 101 at doses of 1 × 10 4 –5 × 10 6 CD 3 + cells/kg (median 31 days post‐transplant). No patient received post‐transplant immunosuppression or developed grade III / IV acute GVHD , demonstrating the feasibility of ATIR 101 infusion for evaluation in two subsequent phase 2 studies. Additionally, we report long‐term follow ‐up of patients treated with ATIR 101 in this study. At 1 year, all 9 patients receiving doses of 0·3–2 × 10 6 CD 3 + cells/kg ATIR 101 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.