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Open Access 25-07-2023 | Graft-Versus-Host Disease | Original Article

The graft-versus-leukemia effect of prophylactic donor lymphocyte infusions after allogeneic stem cell transplantation is equally effective in relapse prevention but safer compared to spontaneous graft-versus-host disease

Authors: Michael Stadler, Lothar Hambach, Elke Dammann, Helmut Diedrich, Haytham Kamal, Iyas Hamwi, Christian Schultze-Florey, Michael Varvenne, Steve Ehrlich, Stefanie Buchholz, Christian Koenecke, Gernot Beutel, Eva M. Weissinger, Jürgen Krauter, Matthias Eder, Bernd Hertenstein, Arnold Ganser

Published in: Annals of Hematology | Issue 9/2023

Abstract

Therapeutic donor lymphocyte infusions (tDLI) are used to reinforce the graft-versus-leukemia (GvL) effect in relapse after allogeneic stem cell transplantation (alloSCT). In contrast, the role of prophylactic DLI (proDLI) in preventing leukemia relapse has been less clearly established, although supported by retrospective, case-control, and registry analyses. We report a prospective, monocentric, ten year cohort of patients with high risk acute leukemias (AL) or myelodysplasia (MDS) in whom proDLI were applied beyond day +120 post alloSCT to compensate for lack of GvL.

272 consecutive allotransplanted AL or MDS patients in complete remission and off immunosuppression at day +120 were stratified according to the prior appearance of relevant GvHD (acute GvHD °II-IV or extensive chronic GvHD) as a clinical indicator for GvL. Escalating doses of unmodified proDLI were applied to 72/272 patients without prior relevant GvHD. Conversely, 157/272 patients with prior spontaneous GvHD did not receive proDLI, nor did 43/272 patients with contraindications (uncontrolled infections, patient refusal, DLI unavailability).

By day 160-landmark analysis (median day of first DLI application), proDLI recipients had significantly higher five-year overall (OS) and disease free survival (DFS) (77% and 67%) than patients with spontaneous GvHD (54% and 53%) or with contraindications (46% and 45%) (p=0.003). Relapse incidence for patients with proDLI (30%) or spontaneous GvHD (29%) was significantly lower than in patients with contraindications (39%; p=0.021). With similar GvHD incidence beyond day +160, non-relapse mortality (NRM) was less with proDLI (5%) than without proDLI (18%; p=0.036).

In conclusion, proDLI may be able to compensate for lack of GvL in alloSCT recipients with high risk AL or MDS.

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Title: The graft-versus-leukemia effect of prophylactic donor lymphocyte infusions after allogeneic stem cell transplantation is equally effective in relapse prevention but safer compared to spontaneous graft-versus-host disease
Authors: Michael Stadler
Lothar Hambach
Elke Dammann
Helmut Diedrich
Haytham Kamal
Iyas Hamwi
Christian Schultze-Florey
Michael Varvenne
Steve Ehrlich
Stefanie Buchholz
Christian Koenecke
Gernot Beutel
Eva M. Weissinger
Jürgen Krauter
Matthias Eder
Bernd Hertenstein
Arnold Ganser
Publication date: 25-07-2023
Publisher: Springer Berlin Heidelberg
Keywords: Graft-Versus-Host Disease
Graft-Versus-Host Disease
Myelodysplastic Syndrome
Leukemia
Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Published in: Annals of Hematology / Issue 9/2023
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-023-05276-5

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