Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia

Christoph Schmid (1) , Myriam Labopin (2, 3) , Nicolaas Schaap (4) , Hendrik Veelken (5) , Arne Brecht (6) , Michael Stadler (7) , Juergen Finke (8) , Frederic Baron (9) , Matthew Collin (10) , Gesine Bug (11) , Per Ljungman (12) , Didier Blaise (13, 14) , Johanna Tischer (15) , Adrian Bloor (16) , Aleksander Kulagin (17) , Sebastian Giebel (18) , Norbert-Claude Gorin (2) , Jordi Esteve (19) , Fabio Ciceri (20) , Bipin Savani (21) , Arnon Nagler (22) , Mohamad Mohty (2, 3)

1 UNIA - University of Augsburg
2 CHU Saint-Antoine [AP-HP]
3 CRSA - Centre de Recherche Saint-Antoine
4 Radboud University Medical Center [Nijmegen]
5 LUMC - Leiden University Medical Center
6 DKD HELIOS Medical Center - DKD Helios Klinik Wiesbaden [Wiesbaden, Germany]
7 MHH - Medizinische Hochschule Hannover = Hannover Medical School
8 University of Freiburg [Freiburg]
9 Université de Liège
10 Newcastle Upon Tyne Hospitals NHS Foundation Trust
11 Goethe-University Frankfurt am Main
12 Karolinska University Hospital [Stockholm]
13 CRCM - Centre de Recherche en Cancérologie de Marseille
14 IPC - Institut Paoli-Calmettes
15 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
16 The Christie NHS Foundation Trust [Manchester, Royaume-Uni]
17 Ratsa Gorbacheva Memorial Children's Institute [St. Petersburg, Russian Federation]
18 MCMCC - Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology
19 Clinic Barcelona Hospital Universitari
20 San Raffaele Scientific Institute
21 Vanderbilt University Medical Center [Nashville]
22 TAU - Tel Aviv University

Abstract We report on 318 patients with acute leukemia, receiving donor lymphocyte infusion (DLI) in complete hematologic remission (CHR) after allogeneic stem cell transplantation (alloSCT). DLI were applied preemptively (preDLI) for minimal residual disease (MRD, n = 23) or mixed chimerism (MC, n = 169), or as prophylaxis in high-risk patients with complete chimerism and molecular remission (proDLI, n = 126). Median interval from alloSCT to DLI1 was 176 days, median follow-up was 7.0 years. Five-year cumulative relapse incidence (CRI), non-relapse mortality (NRM), leukemia-free and overall survival (LFS/OS) of the entire cohort were 29.1%, 12.7%, 58.2%, and 64.3%. Cumulative incidences of acute graft-versus-host disease (aGvHD) grade II–IV°/chronic GvHD were 11.9%/31%. Nineteen patients (6%) died from DLI-induced GvHD. Age ≥60 years ( p = 0.046), advanced stage at transplantation ( p = 0.003), shorter interval from transplantation ( p = 0.018), and prior aGvHD ≥II° ( p = 0.036) were risk factors for DLI-induced GvHD. GvHD did not influence CRI, but was associated with NRM and lower LFS/OS. Efficacy of preDLI was demonstrated by decreasing MRD/increasing blood counts in 71%, and increasing chimerism in 70%. Five-year OS after preDLI for MRD/MC was 51%/68% among responders, and 37% among non-responders. The study describes response and outcome of DLI in CHR and helps to identify candidates without increased risk of severe GvHD.

Domaines: Cancer; Immunologie

Christoph Schmid, Myriam Labopin, Nicolaas Schaap, Hendrik Veelken, Arne Brecht, et al.. Long-term results and GvHD after prophylactic and preemptive donor lymphocyte infusion after allogeneic stem cell transplantation for acute leukemia. Bone Marrow Transplantation, 2022, 57 (2), pp.215-223. ⟨10.1038/s41409-021-01515-3⟩. ⟨hal-03623692⟩