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Durable graft-versus-leukaemia effects without donor lymphocyte infusions - results of a phase II study of sequential T-replete allogeneic transplantation for high-risk acute myeloid leukaemia and myelodysplasia

Davies, JK; Hassan, S; Sarker, S-J; Besley, C; Oakervee, H; Smith, M; Taussig, D; ... Cavenagh, JD; + view all (2018) Durable graft-versus-leukaemia effects without donor lymphocyte infusions - results of a phase II study of sequential T-replete allogeneic transplantation for high-risk acute myeloid leukaemia and myelodysplasia. British Journal of Haematology , 180 (3) pp. 346-355. 10.1111/bjh.14980. Green open access

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Abstract

Allogeneic haematopoietic stem-cell transplantation remains the only curative treatment for relapsed/refractory acute myeloid leukaemia (AML) and high-risk myelodysplasia but has previously been limited to patients who achieve remission before transplant. New sequential approaches employing T-cell depleted transplantation directly after chemotherapy show promise but are burdened by viral infection and require donor lymphocyte infusions (DLI) to augment donor chimerism and graft-versus-leukaemia effects. T-replete transplantation in sequential approaches could reduce both viral infection and DLI usage. We therefore performed a single-arm prospective Phase II clinical trial of sequential chemotherapy and T-replete transplantation using reduced-intensity conditioning without planned DLI. The primary endpoint was overall survival. Forty-seven patients with relapsed/refractory AML or high-risk myelodysplasia were enrolled; 43 proceeded to transplantation. High levels of donor chimerism were achieved spontaneously with no DLI. Overall survival of transplanted patients was 45% and 33% at 1 and 3 years. Only one patient developed cytomegalovirus disease. Cumulative incidences of treatment-related mortality and relapse were 35% and 20% at 1 year. Patients with relapsed AML and myelodysplasia had the most favourable outcomes. Late-onset graft-versus-host disease protected against relapse. In conclusion, a T-replete sequential transplantation using reduced-intensity conditioning is feasible for relapsed/refractory AML and myelodysplasia and can deliver graft-versus-leukaemia effects without DLI.

Type: Article
Title: Durable graft-versus-leukaemia effects without donor lymphocyte infusions - results of a phase II study of sequential T-replete allogeneic transplantation for high-risk acute myeloid leukaemia and myelodysplasia
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/bjh.14980
Publisher version: https://doi.org/10.1111/bjh.14980
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: T-replete, acute myeloid leukaemia, myelodysplasia, sequential conditioning, stem cell transplantation, Adult, Aged, Female, Graft Survival, Graft vs Host Disease, Graft vs Leukemia Effect, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Lymphocyte Depletion, Male, Middle Aged, Myelodysplastic Syndromes, Recurrence, Remission Induction, Transplantation Chimera, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Virus Activation, Young Adult
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > UCL Medical School
URI: https://discovery.ucl.ac.uk/id/eprint/10060656
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