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Primary graft failure, but not relapse, may be identified by early chimerism following double cord blood unit transplantation

Lookup NU author(s): Professor Matthew CollinORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2022 by The American Society of Hematology.Umbilical cord blood transplantation (UCBT) has increased access to potentially curative therapy for patients with life-threatening disorders of the bone marrow and immune system. The introduction of reduced intensity conditioning (RIC) regimens and double umbilical cord unit infusions (DUCBT) has broadened the applicability of UCBT to more frail or larger recipients. The kinetics of chimerism after RIC DUCBT and their clinical utility are poorly understood. The RIC CBT trial reported here sought to prospectively evaluate the role of lineage-specific chimerism after DUCBT in adult patients with hematologic malignancies in the United Kingdom. Fifty-eight patients with a median age of 52 years were recruited, with overall and progression-free survivals of 59% (95% confidence interval [CI], 45%-71%) and 52% (95% CI, 39%-64%), respectively, at 2 years. Nonrelapse mortality was 4% (95% CI, 1%-13%) at day 100, and the relapse rate was 31% (95% CI, 21%-45%) at 1 year. Peripheral blood lineage-specific chimerism was feasible from day 7 after transplant onward. Five patterns of chimerism were observed including (1) complete single unit dominance (39 patients), (2) sustained donor-donor mixed chimerism (3 patients), (3) sustained donor-recipient mixed chimerism (5 patients), (4) dominance reversion (1 patient), and (5) primary graft failure (4 patients). The RIC CBT trial enabled adult patients with high-risk hematologic malignancies to safely access UCBT in the United Kingdom and provided novel insights into the kinetics of donor and recipient chimerism after RIC DUCBT that are clinically relevant. This trial was registered at https://www.clinicaltrialsregister.eu/ctr-search/trial/2004-003845-41/GB as #NCT00959231 and EudraCT 2004-003845-41.


Publication metadata

Author(s): Hough R, Lopes A, Patrick P, Russell N, Raj K, Tholouli E, Snowden JA, Collin M, El-Mehidi N, Lawrie A, Clifton-Hadley L, Veys P, Craddock C, Mackinnon S, Cook G, Shaw B, Marks D

Publication type: Article

Publication status: Published

Journal: Blood Advances

Year: 2022

Volume: 6

Issue: 7

Pages: 2414-2426

Print publication date: 08/04/2022

Online publication date: 26/10/2021

Acceptance date: 19/08/2021

Date deposited: 03/07/2023

ISSN (print): 2473-9529

ISSN (electronic): 2473-9537

Publisher: American Society of Hematology

URL: https://doi.org/10.1182/bloodadvances.2021005106

DOI: 10.1182/bloodadvances.2021005106

PubMed id: 34700343


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