Introduction: Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) remains the best curative option for high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Unfortunately, it is still associated with a significant risk of relapse due to mechanisms of escape from the control of alloreactive T cells. Repetitive adjuvant donor lymphocyte infusion (DLI), termed prophylactic DLI (proDLI), as an effective strategy in preventing relapse is still debated. Methods: We performed a retrospective multicenter study to evaluate the efficacy of proDLI in allografted AML and MDS. We identified 56 patients treated with proDLI (DLI planned in full chimeras without any sign of disease relapse) and matched them to 167 patients in control group, (DLI performed for mixed chimerism or positive minimal residual disease) based on similar age, initial disease, cytogenetic prognosis, and conditioning intensity. Results: In univariate analysis, the incidence of severe aGVHD at 100 days and incidence of all grades of chronic GVHD 1 year after allo-HSCT were similar in the two groups. We also observed a trend of higher 3-year RI (52.61% [95% confidence interval 25.99–79.23]) in the proDLI group versus the control group (29.31% [20.28–38.34], p = 0.067). However, 3-year overall survival (p = 0.892), progression-free survival (p = 0.239), and nonrelapse mortality (p = 0.343) were similar between the two groups. In multivariate analysis, the only factor influencing overall and progression-free survival was anti-thymocyte globulin administration during the conditioning regimen. Conclusion: The proDLI strategy had an acceptable toxicity profile but did not improve patient outcomes compared to the pre-emptive strategy.

1.
Bejanyan N, Weisdorf DJ, Logan BR, Wang HL, Devine SM, de Lima M, et al. Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. Biol Blood Marrow Transpl. 2015;21(3):454–9.
2.
Miyamoto T, Fukuda T, Nakashima M, Henzan T, Kusakabe S, Kobayashi N, et al. Donor lymphocyte infusion for relapsed hematological malignancies after unrelated allogeneic bone marrow transplantation facilitated by the Japan marrow donor program. Biol Blood Marrow Transpl. 2017;23(6):938–44.
3.
Dazzi F, Szydlo RM, Cross NCP, Craddock C, Kaeda J, Kanfer E, et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood. 2000;96(8):2712–6.
4.
Porter DL, Collins RH Jr., Hardy C, Kernan NA, Drobyski WR, Giralt S, et al. Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood. 2000;95(4):1214–21.
5.
Schmid C, Labopin M, Nagler A, Bornhauser M, Finke J, Fassas A, et al., EBMT Acute Leukemia Working Party. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol. 2007;25(31):4938–45.
6.
Takami A, Yano S, Yokoyama H, Kuwatsuka Y, Yamaguchi T, Kanda Y, et al. Donor lymphocyte infusion for the treatment of relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation: a retrospective analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2014;20(11):1785–90.
7.
Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, et al. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 2012;119(14):3256–62.
8.
Massenkeil G, Nagy M, Lawang M, Rosen O, Genvresse I, Geserick G, et al. Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved. Bone Marrow Transpl. 2003;31(5):339–45.
9.
Bethge WA, Hegenbart U, Stuart MJ, Storer BE, Maris MB, Flowers MED, et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood. 2004;103(3):790–5.
10.
Krishnamurthy P, Potter VT, Barber LD, Kulasekararaj AG, Lim ZY, Pearce RM, et al. Outcome of donor lymphocyte infusion after T cell-depleted allogeneic hematopoietic stem cell transplantation for acute myelogenous leukemia and myelodysplastic syndromes. Biol Blood Marrow Transpl. 2013;19(4):562–8.
11.
Schaap N, Schattenberg A, Bar B, Preijers F, van de Wiel van Kemenade E, de Witte T. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia. 2001;15(9):1339–46.
12.
Liga M, Triantafyllou E, Tiniakou M, Lambropoulou P, Karakantza M, Zoumbos NC, et al. High alloreactivity of low-dose prophylactic donor lymphocyte infusion in patients with acute leukemia undergoing allogeneic hematopoietic cell transplantation with an alemtuzumab-containing conditioning regimen. Biol Blood Marrow Transpl. 2013;19(1):75–81.
13.
Legrand F, Le Floch AC, Granata A, Furst S, Faucher C, Lemarie C, et al. Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation for high-risk AML. Bone Marrow Transpl. 2017;52(4):620–1.
14.
Eefting M, Halkes CJM, de Wreede LC, van Pelt CM, Kersting S, Marijt EWA, et al. Myeloablative T cell-depleted alloSCT with early sequential prophylactic donor lymphocyte infusion is an efficient and safe post-remission treatment for adult ALL. Bone Marrow Transpl. 2014;49(2):287–91.
15.
Baron F, Beguin Y. Prophylactic donor lymphocyte infusion in patients with high-risk acute myeloid leukemia: ready for prime time? Bone Marrow Transpl. 2016;51(5):640–2.
16.
Jedlickova Z, Schmid C, Koenecke C, Hertenstein B, Baurmann H, Schwerdtfeger R, et al. Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation. Bone Marrow Transpl. 2016;51(5):663–7.
17.
Schmid C, Labopin M, Schaap N, Veelken H, Schleuning M, Stadler M, et al., EBMT Acute Leukaemia Working Party. Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation in acute leukaemia - a matched pair analysis by the Acute Leukaemia Working Party of EBMT. Br J Haematol. 2019;184(5):782–7.
18.
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88.
19.
Mrozek K, Marcucci G, Nicolet D, Maharry KS, Becker H, Whitman SP, et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012;30(36):4515–23.
20.
Peggs KS, Thomson K, Hart DP, Geary J, Morris EC, Yong K, et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. Blood. 2004;103(4):1548–56.
21.
Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453–74.
22.
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108(2):419–25.
23.
Rettinger E, Willasch AM, Kreyenberg H, Borkhardt A, Holter W, Kremens B, et al. Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation. Blood. 2011;118(20):5681–8.
24.
Rujkijyanont P, Morris C, Kang G, Gan K, Hartford C, Triplett B, et al. Risk-adapted donor lymphocyte infusion based on chimerism and donor source in pediatric leukemia. Blood Cancer J. 2013;3(8):e137.
25.
Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F, et al. Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia. Blood. 2007;109(11):5063–4.
26.
Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ. Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol. 2005;23(24):5675–87.
27.
Schmid C, Schleuning M, Tischer J, Holler E, Haude KH, Braess J, et al. Early allo-SCT for AML with a complex aberrant karyotype--results from a prospective pilot study. Bone Marrow Transpl. 2012;47(1):46–53.
28.
Xuan L, Fan Z, Zhang Y, Zhou H, Huang F, Dai M, et al. Sequential intensified conditioning followed by prophylactic DLI could reduce relapse of refractory acute leukemia after allo-HSCT. Oncotarget. 2016;7(22):32579–91.
You do not currently have access to this content.