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
-
Published:2023-07-25
Issue:9
Volume:102
Page:2529-2542
-
ISSN:0939-5555
-
Container-title:Annals of Hematology
-
language:en
-
Short-container-title:Ann Hematol
Author:
Stadler MichaelORCID, Hambach Lothar, Dammann Elke, Diedrich Helmut, Kamal Haytham, Hamwi Iyas, Schultze-Florey Christian, Varvenne Michael, Ehrlich Steve, Buchholz Stefanie, Koenecke Christian, Beutel Gernot, Weissinger Eva M., Krauter Jürgen, Eder Matthias, Hertenstein Bernd, Ganser Arnold
Abstract
AbstractTherapeutic 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.
Funder
Medizinische Hochschule Hannover (MHH)
Publisher
Springer Science and Business Media LLC
Subject
Hematology,General Medicine
Reference45 articles.
1. Benjanyan N, Weisdorf DJ, Logan BR, Wang H-L, Devine SM, de Lima M, Bunjes DW, Zhang M-J (2015) Survival of patients with acute leukemia relapsing after allogeneic hematopoietic cell transplantation: a Center for International Blood and Marrow Transplant Research study. Biol Blood Marrow Transplant 21:454–459. https://doi.org/10.1016/j.bbmt.2014.11.007 2. Kharfan-Dabaja MA, Labopin M, Polge E, Nishihori T, Bazarbachi A, Finke J, Stadler M, Ehninger G, Lioure B, Schaap N, Afanasyev B, Yeshurun M, Isaksson C, Maertens J, Calandon Y, Schmid C, Nagler A, Mohty M (2018) Association of second allogeneic hematopoietic cell transplant vs donor lymphpocyte infusion with overall survival in patients with acute myeloid leukemia relapse. JAMA Oncol 4(9):1245–1253. https://doi.org/10.1001/jamaoncol.2018.2091 3. Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY, Carabasi MH, Gale RP, Giralt S, Hale GA, Ilhan O, McCarthy PL, Socié G, Verdonck LF, Weisdorf DJ, Horowitz MM (2002) Severity of chronic graft-versus-host diasease: association with treatment-related mortality and relapse. Blood 100:406–414. https://doi.org/10.1182/blood.V100.2.406 4. Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A, Olavarria E, van Rhee F, Kanfer E, Apperley JF, Goldman JM (2000) Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 95:67–71. https://doi.org/10.1182/blood.V95.1.67 5. Schmid C, Kuball J, Bug G (2021) Defining the role of donor lymphocyte infusion in high-risk hematologic malignancies. J Clin Oncol 39:397–418. https://doi.org/10.1200/JCO.20.01719
|
|