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Adoptive immunotherapy via Donor lymphocyte infusions following allogeneic haematopoietic stem cell transplantation for Myelofibrosis: A real world, retrospective multi-centre study

Rampotas, A; Sockel, K; Panitsas, F; Theuser, C; Bornhauser, M; Hernani, R; Hernandez- Boluda, JC; ... McLornan, DP; + view all (2023) Adoptive immunotherapy via Donor lymphocyte infusions following allogeneic haematopoietic stem cell transplantation for Myelofibrosis: A real world, retrospective multi-centre study. Transplantation and Cellular Therapy 10.1016/j.jtct.2023.08.020. (In press).

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Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only curative option for Myelofibrosis (MF). Relapse however remains a significant problem in up to 20-30% of cases. Donor Lymphocyte Infusions (DLI) represent a potentially effective strategy for relapse prevention and management, but optimal timing based on measurable residual disease (MRD)/chimerism analyses and regimen choice remain undetermined. We performed a retrospective ‘real world’ analysis of a multicentre cohort of MF allo-HCT patients from 8 European transplant centres who received DLI between 2005-2022. Response was assessed using IWG-MRT defined response criteria, and survival endpoints were estimated using the Kaplan-Meier estimator and log-rank test. The study included 28 patients with a median age of 58 years and a Karnofsky performance status of >80. The majority of patients had DIPPS-plus Intermediate-2 or high-risk disease at the time of allo-HCT. In vivo T cell depletion was utilised in 20 (71.2%) cases, with 19/20 patients receiving anti-thymocyte globulin (ATG). Indication for DLI was either ‘pre-emptive’ (n=15), due to a decrease in recipient chimerism (n=13) or molecular relapse (n=2), or ‘therapeutic’ (n=13) for clinician-defined haematological/ clinical relapse. No patient received DLI prophylactically. Median time to DLI administration was 23.4 months post allo-HCT. Of the 16 patients receiving >1 dose of DLI, 12 were part of a planned escalating dose regimen. Median follow-up from time of 1st DLI administration was 55.4 months. Response rates to DLI were CR (n=9), PR (n=1), and clinical improvement (n=6). Chimerism levels improved in 16 patients, and stable disease was reported in 5 patients. No response or progression was reported in 7 patients. DLI-induced aGVHD was reported in 11 (39%) cases, grade 3/4 (n=7;25%). Median overall survival from time of 1st DLI was 62.6 months, and the cumulative incidence of relapse/progression after 1st DLI was 30.8% at 6 months. This study highlights that good response rates can be achieved with DLI even after frank relapse in some patients within a cohort where other treatment options are very limited. More prospective studies are warranted to identify the optimal DLI regimen and timing to improve patient outcomes.

Type: Article
Title: Adoptive immunotherapy via Donor lymphocyte infusions following allogeneic haematopoietic stem cell transplantation for Myelofibrosis: A real world, retrospective multi-centre study
DOI: 10.1016/j.jtct.2023.08.020
Publisher version: https://doi.org/10.1016/j.jtct.2023.08.020
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: MF, DLI, alloHSCT
UCL classification: UCL
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 > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: https://discovery.ucl.ac.uk/id/eprint/10176280
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