Journal article

Recipient BCL2 inhibition and NK cell ablation form part of a reduced intensity conditioning regime that improves allo-bone marrow transplantation outcomes

Yuhao Jiao, Joanne E Davis, Jai Rautela, Emma M Carrington, Mandy J Ludford-Menting, Wilford Goh, Rebecca B Delconte, Fernando Souza-Fonseca-Guimaraes, Rachel Koldej, Daniel Gray, David Huang, Ben T Kile, Andrew M Lew, David S Ritchie, Nicholas D Huntington

Cell Death & Differentiation | NATURE PUBLISHING GROUP | Published : 2019

Abstract

Allogeneic hematopoietic stem cell transplantation (alloSCT) is used to treat over 15,000 patients with acute myeloid leukemia (AML) per year. Donor graft-versus-leukemia (GVL) effect can prevent AML relapse; however, alloSCT is limited by significant toxicity related to conditioning intensity, immunosuppression, opportunistic infections, and graft-versus-host disease (GVHD). Reducing the intensity of conditioning regimens prior to alloSCT has improved their tolerability, but does not alter the pattern of GVHD and has been associated with increased rates of graft rejection and relapse. Here, using a murine pre-clinical model, we describe a novel recipient conditioning approach combining redu..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by NHMRC Early Career Fellowship


Awarded by National Breast Cancer Foundation (NBCF) Fellowship


Awarded by NHMRC


Awarded by Priority-driven Collaborative Cancer Research Scheme


Funding Acknowledgements

This work is supported by program and project grants from the National Health and Medical Research Council (NHMRC) of Australia (1049407, 1066770, 1057852, 1027472 to N.D.H.), as well as an NHMRC Independent Research Institute Infrastructure Support scheme grant and a Victorian State Government Operational Infrastructure Scheme grant. J.E.D. is supported by a Rabinowicz & Amarant Family Cancer Research Fellowship from the Royal Melbourne Hospital Foundation. F.S.-F.G. was supported by a NHMRC Early Career Fellowship (1088703), a National Breast Cancer Foundation (NBCF) Fellowship (PF-15-008), and grant #1120725 awarded through the Priority-driven Collaborative Cancer Research Scheme and funded by Cure Cancer Australia with the assistance of Cancer Australia. N.D.H. is a recipient of a Melanoma Research Grant from the Harry J Lloyd Charitable Trust (USA), Melanoma Research Alliance (USA), a research grant from the Ian Potter Foundation (AUS) and a CLIP grant from Cancer Research Institute (USA). This work is also supported by fellowships from the NHMRC (10461276 to N. D.H.), the Menzies Foundation (to N.D.H.), and by an enabling grant from The Fight Cancer Foundation.