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.
Highlights
The graft-versus-leukemia (GvL) effect is the therapeutic cornerstone of allogeneic stem cell transplantation in acute leukemia (AL) [1]
donor lymphocyte infusion (DLI) was given to patients who showed early signs of relapse such as persisting minimal residual disease (MRD), reappearance of molecular markers of the leukemia, or mixed chimerism (MC), which has been referred to as preemptive DLI [7, 8]
To evaluate the pure effect of donor cells, patients from the registry who had received any additional antileukemic therapy after SCT before or at time of DLI, such as tyrosine kinase inhibitors (TKI), hypomethylating agents (HMA), or chemotherapy had been excluded from the analysis
Summary
The graft-versus-leukemia (GvL) effect is the therapeutic cornerstone of allogeneic stem cell transplantation (alloSCT) in acute leukemia (AL) [1]. These experiences prompted clinicians to exploit the GvL reaction in a less proliferative stage, i.e., by giving DLI to patients in complete hematological remission (CHR) These patients were either at high risk of relapse because of T-cell depletion (TCD) of the graft, unfavorable genetics of the leukemia, or advanced disease at SCT; this approach has been referred to as adjuvant or prophylactic DLI (proDLI). The Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) performed a registry-based survey on 318 patients with AL, who received DLI in CHR after alloSCT. Three-hundred and eighteen patients suffering from acute myeloid leukemia (AML, 78%) or acute lymphoblastic leukemia (ALL, 22%) with a median age of 47.5 years (range: 18.2–70.6, 49 were older than 60) were identified They had received DLI in CHR for MC (n = 169, 53%), persisting or recurrent MRD (n = 23, 7%), or as prophylaxis (n = 126, 40%).
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